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Pharmacology

Research in pharmacology, drug discovery, receptors and channel function.

All Labs in This Area

 Mohamed Abazeed Lab

Individualize cancer care (radiotherapy) by helping physicians recommend treatments based on the genetic and imaging features of individual tumors.

Research Description

Mohamed E Abazeed, MD, PhD
Mohamed E Abazeed, MD, PhD

Precision oncology facilitates individualized treatment decisions on the basis of patient and tumor specific factors for an increasing proportion of cancer patients. Despite growing evidence that inter-patient variation affects treatment responses after radiotherapy, patients receiving these treatments continue to be treated with the same or similar doses. We seek to develop an information capability at the forefront of personalized radiotherapy treatments. We achieve this through the assembly of experimental scaffolds that span the translational research spectrum and help us understand tumor complexity and predict clinical outcomes.

Briefly, we conduct large-scale projects that capture the diversity of our patients and provide a rich substrate for computational and mathematical models of cancer’s propensity to resist our treatments. Three large-scale projects have been completed or are currently in progress including: 1) The X-ray Target Discovery and Development (XTD2) project, which profiled 533 cancer cell line survival  comprising 26 cancer types to ionizing radiation. This project represented the largest profiling effort of cancer cell line survival after irradiation ever conducted. 2) The Pan-cancer Radiogenomic Atlas is a gene variant profiling project that interrogated >1000 common and rare genetic variants for response to ionizing radiation in immortalized human cells (non-cancer cells). Current work is building on the unary profiling methodology to study the interaction between varied gene variants, thus building toward greater complexity. 3) The 10,000 Avatar Project was inaugurated by our group in 2019. This will be the largest patient-derived xenograft (PDX) mouse experiment conducted to date by any group. ~10,000 mice engrafted with ~500 genetically annotated PDXs will be irradiated using a singular experimental platform. This work will correlate genetic and other omic (e.g. transcriptomic, metabolomic, et cetera) alterations with the likelihood of response to radiotherapy and matched recurrent tumors.

Concurrent with the large-scale biological profiling approaches described above, we have developed a clinomic dataset that integrates clinical information (e.g. demographics, treatments, outcomes) and patient avatar models (patient-derived xenografts) with omic outputs for individual patients. The latter include radiomics (embedded quantitative data derived from imaging modalities like computed tomography), genomics (genetic information derived from the patient’s tumor or germline), transcriptomics (gene expression), and others. Using this information, we seek to design and implement tools that can augment the physician’s ability to estimate the probability of treatment failures and modulate failure by individualized treatment recommendations.

For lab information and more, see Mohamed Abazeed's, MD,PhD, faculty profile.

Publications

See Dr. Abazeed's publications in PubMed.

Contact

Contact the Abazeed Lab at 312-503-2195. You may also contact Dr. Abazeed directly via email.

Post-doctoral Fellows

Priyanka Gopal, Rohan Bareja

Students

Alexandru Buhimschi

Technical Staff

Titas Bera, Dylan Schellenberg, Trung Hoang

 Sarki Abdulkadir Lab

Studying the mechanisms of prostate cancer initiation, progression and recurrence and strategies to therapeutically target these processes

Research Description

Our laboratory focuses on understanding the molecular mechanisms that drive prostate cancer initiation, progression and recurrence with the ultimate goal of developing therapeutic strategies that target these processes. Our approach includes the genomic analysis of human tumors, cell culture studies and the use of genetically engineered mouse models. We have a strong interest in genomics and gene regulation, oncogenic kinases as potential molecular therapeutic targets and the use of in vivo lineage tracing to define the fates of specific cell populations in tumorigenesis.

Specific projects include:

The role of the oncogenic serine/threonine kinase PIM1 in prostate cancer - PIM1 is coexpressed with c-MYC and dramatically enhances c-MYC-driven prostate tumorigenesis in a kinase-dependent manner. Notably, PIM1 is induced in tumors by hypoxia, radiation and treatment with docetaxel, a common but largely ineffective option for patients with advanced castration-resistant prostate cancer. PIM1 induction by hypoxia/radiation/docetaxel promotes prostate cancer cell survival and therapeutic resistance. Therefore, PIM1 may represent a valuable therapeutic target in prostate cancer. We are using new mouse models of prostate cancer for testing the efficacy of novel PIM1 kinase inhibitors in treating prostate cancer and reversing therapeutic resistance. We have also identified novel candidate PIM1-interacting proteins in prostate epithelial cells. Among the proteins identified are a MYC transcriptional cofactor and a prostate stem cell marker/regulator. We are investigating how PIM1 promotes prostate tumorigenesis by phosphorylating these substrates involved in regulating MYC transcriptional activity and stem cell function.

Cellular and molecular determinants of prostate cancer recurrence - A major clinical problem in prostate cancer is that of tumor recurrence following initial apparently successful therapy. Recurrent tumors may arise from a small number of "cancer stem-like cells" that survive the initial therapeutic intervention and have the capacity to regenerate the tumor. We are using lineage tracing to examine the competence of specific prostate epithelial cell types to regenerate tumors following therapy in mice.

Targeting lethal prostate cancer – We are using our mouse model of lethal prostate cancer based on alterations in Myc, Pten and Tp53 to develop new targeted therapies. One current project involves the targeting of EphB4 receptor tyrosine kinase using an antagonist as a therapeutic strategy.

For more information, see Dr. Abdulkadir's faculty profile.

Publications

Rodríguez Y, Unno K, Truica MI, Chalmers ZR, Yoo YA, Vatapalli R, Sagar V, Yu J, Lysy B, Hussain M, Han H, Abdulkadir SA. A Genome-Wide CRISPR Activation Screen Identifies PRRX2 as a Regulator of Enzalutamide Resistance in Prostate Cancer. Cancer Res. 2022 Jun 6;82(11):2110-2123.

Chalmers ZR, Burns MC, Ebot EM, Frampton GM, Ross JS, Hussain MHA, Abdulkadir SA. Early-onset metastatic and clinically advanced prostate cancer is a distinct clinical and molecular entity characterized by increased TMPRSS2-ERG fusions. Prostate Cancer Prostatic Dis. 2021 Jun;24(2):558-566.

Unno K, Chalmers ZR, Pamarthy S, Vatapalli R, Rodriguez Y, Lysy B, Mok H, Sagar V, Han H, Yoo YA, Ku SY, Beltran H, Zhao Y, Abdulkadir SA. Activated ALK Cooperates with N-Myc via Wnt/β-Catenin Signaling to Induce Neuroendocrine Prostate Cancer. Cancer Res. 2021 Apr 15;81(8):2157-2170.

Sagar V, Vatapalli R, Lysy B, Pamarthy S, Anker JF, Rodriguez Y, Han H, Unno K, Stadler WM, Catalona WJ, Hussain M, Gill PS, Abdulkadir SA. EPHB4 inhibition activates ER stress to promote immunogenic cell death of prostate cancer cells. Cell Death and Disease. November 2019.

Han H, Jain AD, Truica MI, Izquierdo-Ferrer J, Anker JF, Lysy B, Sagar V, Luan Y, Chalmers ZR, Unno K, Mok H, Vatapalli R, Yoo YA, Rodriguez Y, Kandela I, Parker JB, Chakravarti D, Mishra RK, Schiltz GE, Abdulkadir SA. Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy. Cancer Cell.  November 2019.

Njoroge RN, Vatapalli RJ, Abdulkadir SA. Organoids increase the predictive value of in vitro cancer chemoprevention studies for in vivo outcome. Frontiers in Oncology. January 2019.

See Dr. Abdulkadir's publications in PubMed.

Contact Us

Dr. Abdulkadir
Lab Telephone: 312-503-5031

 Mazhar Adli Lab

Studying how to prevent cancer development and chemotherapy resistance using genomic and epigenomic approaches

Research Description

I am interested in understanding the key drivers of cancer and identifying novel therapeutic drug combinations to prevent cancer development and chemotherapy resistance. To achieve these goals, our lab is using and developing genomic and epigenomic mapping, editing and imaging approach to understand genome regulation in normal and malignant settings. We integrate experimental approaches with large-scale computational data analysis to verify our experimental observations and come up with new testable hypotheses.  Our laboratory is utilizing and also developing cutting-edge functional genomics strategies and developing novel CRISPR based manipulation tools to understand dynamic gene regulation and 3D genome organization in normal and malignant settings. These efforts are based on our previous expertise in genome-wide approaches and development of novel technologies for cancer research. Our lab has developed particular expertise in utilizing and developing CRISPR based technologies.

For more information, see Dr. Adli's faculty profile or the Adli lab website.

Publications

See Dr. Adli's publications in PubMed.

 

Contact Us

Dr. Adli

 Daniel Arango Lab

Investigating the role of post-transcriptional modifications of RNA in the proliferation, differentiation, and survival of cancer cells

Research Description

Translation is the mechanism by which proteins are made from the information stored in the genetic code. This process is achieved with the help of RNA molecules such as ribosomal RNA (rRNA), transfer RNA (tRNA), and messenger RNA (mRNA). While translation is a tightly regulated process, global perturbations in protein synthesis are observed in stress conditions, cancer, and aging, highlighting the regulatory mechanisms of translation as potential targets in cancer and age-related disorders. One poorly characterized layer of translation regulation is the epitranscriptome, defined as the set of more than 140 ribonucleotide modifications that alter the biochemical properties and function of all classes of RNA, including rRNA, tRNA, and mRNA. While the distribution and function for most ribonucleotide modifications are undefined, the enzymes responsible for depositing RNA modifications are dynamic and sensitive to metabolic alterations, potentially regulating the temporal response to stress or the onset of human diseases such as cancer.

Our group investigates the mechanisms by which RNA modifications regulate protein synthesis and how these mechanisms affect cell fate decisions such as cell proliferation, survival, and differentiation in cancer and stress conditions. By integrating RNA biology, transcriptomics, and cell biology, we aim to uncover novel mechanisms of gene expression regulation and generate new tools that can be harnessed to develop anti-cancer therapies.

For more information, see Dr. Arango's faculty profile and laboratory website.

Current Projects

  • Mechanisms and regulation of RNA acetylation in cancer cells
  • Regulation of stress response by RNA modifications
  • Targeting RNA-modifying enzymes and RNA modifications for therapeutic purposes

Publications

See Dr. Arango's publications.

Contact

Contact Dr. Arango at 312-503-0732.

 Hossein Ardehali Lab

Role of mitochondria and metabolic processes in cancer growth, cardiac disease and immunological processes

 

Research Description

Our lab focuses on three major areas of research:

Role of hexokinase enzymes in immune function, cancer growth and stem cell differentiation

Hexokinase (HK) enzymes phosphorylate glucose to trap it inside the cell. There are 5 mammalian HKs (named HK1-5), with two of them having a hydrophobic region at their N-terminus that allows them to bind to the mitochondria. We have made mouse models and developed in vitro systems to allow us to study the role of mitochondrial binding of HKs in glucose metabolism. We have determined that HK1 binding to the mitochondria determines whether glucose is used for anabolic processes (ie, pentose-phosphate pathway) or catabolism (ie, glycolysis). Thus, the non-enzymatic function of this protein and its subcellular location determines the fate of glucose. We are now studying this process in T-cells, vascular cells and cancer cells. We are also in the process of generating several mouse models of hexokinase enzymes, including HK2 without the mitochondrial binding domain and HK3 knockout mice. We will study these models in different disease and physiological conditions.

Characterization of cellular and mitochondrial iron regulation

Our lab has identified a novel mitochondrial protein, ATP-Binding Cassette-B8 (ABCB8), which plays a role in mitochondrial iron homeostasis and mitochondrial iron export. Mice with ABCB8 knocked out in the heart develop cardiomyopathy and mitochondrial iron accumulation. In addition, we have shown that a pathway involving mTOR and tristetraprolin, treatment with doxorubicin (an anticancer drug that also causes cardiomyopathy) and SIRT2 protein also impact cellular and/or mitochondrial iron regulation. Current studies in this area include: 1) further characterization of ABCB8 in iron homeostasis in other organs and disorders, 2) characterization of the mechanism for iron regulation by SIRT2, 3) identification of the mechanism by which mTOR is regulated by iron through epigenetic changes, 4) role of iron in viral infection, particularly HIV, 5) characterization of the effects of iron on mitochondrial dynamics and 6) identification of novel mitochondrial-specific iron chelators.

Role of mRNA-binding proteins in cellular and systemic metabolism

TTP is a protein that binds to AU-rich regions in the 3’ UTR of mRNA molecules and causes their degradation. It has been studied extensively in the field of inflammation. We recently showed that it also plays a role in cellular iron conservation. We have also shown that TTP is a key mediator of cellular metabolic processes. Our studies have demonstrated that TTP regulates glucose, fatty acid and branched-chain amino acid metabolism in the liver and muscle tissue. We also have evidence that TTP directly regulates mitochondrial electron transport chain (ETC) by targeting specific proteins in the ETC complexes. Finally, recent studies demonstrated that TTP also regulates systemic metabolism by targeting FGF-21 expression. We have both TTP Floxed mice (for the generation of tissue specific TTP knockout mice) and TTP knockout mice in the background of TNF-alpha receptor 1/2 knockout mice (to reduce the inflammatory burden).  Current studies include: 1) role of TTP in liver metabolism of fatty acids and glucose, 2) effects of TTP on mitochondrial proteins, 3) mechanism of TTP regulation of branched-chain amino acid levels and 4) role of TTP in cardiac metabolism.

For more information, see Dr. Ardehali's faculty profile.

Publications

See Dr. Ardehali's publications in PubMed.

Contact

Dr. Ardehali

 Rishi Arora Lab

Understanding the molecular and signaling pathways involved in atrial fibrillation.

 

The primary focus of the Arora lab is to obtain a better understanding of the molecular mechanisms underlying heart rhythm disorders (cardiac arrhythmias). The cardiac arrhythmia most closely studied in the Arora lab is atrial fibrillation (AF). AF is the most common rhythm disorder of the heart that affects >6 million American and is a major cause of stroke. Unfortunately, current therapies for AF have suboptimal efficacy. This is thought to be because current therapies are not targeted at the major molecular mechanisms underlying AF. The focus of research in the Arora lab has therefore been to not only better understand the molecular mechanisms underlying AF but to discover new, mechanism-guided therapies for this condition. Dr. Arora’s laboratory is one of the few in the world dedicated to understanding the molecular mechanisms underlying AF and to translating these research findings to the clinic.

Over the last 15 years, the Arora lab has discovered that autonomic nervous system signaling, oxidative injury, altered excitation-contraction coupling and TGF-β signaling are key mechanisms underlying the genesis of AF. Because AF is predominantly a disorder of the larger, mammalian heart, the Arora lab laboratory primarily uses large animal models of AF to understand mechanisms of AF. Over the last few years, the Arora lab has developed new gene-based therapies for this condition. This has included not only the gene-based targeting of key molecular signaling pathways underlying AF, but has also included the development of new devices and energy sources (such as electroporation) to perform targeted gene delivery in the heart.

In its quest to develop new, mechanism guided therapies for AF, the Arora lab is also engaged in the development of new, signal processing algorithms to study the electrical signals (electrograms) in the fibrillating heart. Over the last several years, the lab have published many papers on how AF electrograms can be used to determine pathophysiological substrate for AF.

Dr. Arora has mentored more than 40 trainees in his lab over the last 17 years, and currently serve as training director on a major grant from the American Heart Association. The lab is an ideal home for graduate students interesting in the following areas of biology:

Cardiovascular physiology, with a focus on cardiac electrophysiology: The lab uses a variety of cutting edge techniques to study the electrophysiology of the heart from cell-to-bedside. This includes high resolution electrophysiological mapping in the intact heart (in-vivo), high resolution optical mapping in the explanted heart (ex-vivo) and cellular electrophysiological techniques in isolated cardiomyocytes to assess excitation contraction coupling (calcium cycling) and whole cell ion channel electrophysiology. Biomedical engineering, instrumentation: The lab uses a variety of signal processing techniques to assess intracardiac electrograms from animals and humans with AF. The lab also investigates the behavior of autonomic nerves in the heart, using digital signal processing. In addition to signal processing, the lab is also actively engaged in the development of new devices (hardware) to perform gene delivery in the heart.

Gene therapy: A major focus of the lab is to develop new gene therapy approaches for cardiac arrhythmias. This includes the identification of novel gene targets in AF, use of new delivery vectors (non-viral and viral) for targeted gene therapy in the heart, and the development of new, catheter-based gene delivery techniques.

For more information, see Dr. Arora's faculty profile.

Publications

See Dr. Arora's publications in PubMed.

 Daniel Batlle Lab

Focusing on the renin angiotensin system as it relates to the understanding of human diabetic kidney disease and rodent models of diabetic kidney disease and hypertension

Research Description

Dr. Batlle’s lab currently focuses on the renin angiotensin system as it relates to the understanding of this system in rodent kidney physiology. Of particular focus are the pathways and mechanisms that determine the enzymatic cleavage and degradation of Angiotensin II and other peptides within the system by ACE2-dependent and independent pathways. The lab uses a holistic approach involving ex vivo, in vitro and in vivo studies using various rodent models of diabetic and hypertensive kidney disease.

The lab is also involved in the search for biomarkers of kidney disease progression as part of the NIDDK Consortium on CKD. Other areas of research interest include nocturnal hypertension and the physiology and pathophysiology of electrolyte disorders such as distal renal tubular acidosis.

For more information, please see Dr. Batlle's faculty profile.

Publications

See Dr. Batlle's publications in PubMed.

Contact

Dr. Batlle

 Bruce Bochner Lab

The Bochner lab studies cells and siglec receptors (especially Siglec-8 and Siglec-F) involved in allergic inflammation, focusing mainly on eosinophils, mast cells and basophils in humans and mice.

Our primary research interests are in eosinophil- and mast cell-associated diseases, including asthma, hypereosinophilic syndromes and systemic mastocytosis. We have a particular interest and focus on understanding the function of Siglec-8, an inhibitory and sometimes pro-apoptotic receptor expressed on human eosinophils, basophils and mast cells and how it can be targeted for clinical benefit. Animal models are used to study its closest counterparts, such as Siglec-F. In studies involving carbohydrate biochemistry and glycoproteomics, the lab is isolating and characterizing potential glycan ligands for Siglec-F and Siglec-8. Finally, we are interested in food allergy and anaphylaxis and are exploring new ways to prevent allergic reactions in vitro and in vivo. 


Publications

View lab publications via PubMed

For more information, please see Dr. Bochner's faculty profile or view more information regarding our NHLBI-funded work.

Contact Us

Email Dr. Bochner
Phone 312-503-0068 or the Bochner Lab at 312-503-1396.

Lab Staff

Melanie C. Dispenza, MD, PhD
Postdoctoral Fellow
312-503-0066

Piper Robida, PhD
Postdoctoral Fellow
312-503-0066

Krishan Chhiba, BS
MD/PhD Candidate
312-503-8032

Yun Cao, MS
Research Lab Manager 1
312-503-1396

Rebecca Krier, MS
Research Lab Manager 1
312-503-8032

Jeremy O’Sullivan, PhD
Research Assistant Professor
312-503-0066

Soon Cheon Shin, PhD
Research Associate
312-503-1131

 Irina Budunova Lab

Studying the role of the glucocorticoid receptor in carcinogenesis  and stem cell maintenance. Involved in development GR-targeted therapies in skin.

Research Description

The current projects in Dr. Budunova’s lab are centered on the role of the glucocorticoid receptor (GR) as a tumor suppressor gene in skin. We showed that skin-specific GR transgenic animals are resistant to skin carcinogenesis and GR KO animals are more sensitive to skin tumor development.  We are also interested in the role of GR in the maintenance of skin stem cells (SC). We found that GR/glucocorticoids inhibit the expression of numerous SC markers in skin including CD34- a marker of hair follicular epithelial SC and reduce the proliferative potential of skin SCs.

The glucocorticoids remain among the most effective and frequently used anti-inflammatory drugs in dermatology. Unfortunately, patients chronically treated with topical glucocorticoids, develop side effects including cutaneous atrophy. GR controls gene expression via (i) transactivation that requires GR dimerization and binding as homo-dimer to gene promoters and (ii) transrepression that is chiefly mediated via negative interaction between GR and other transcription factors including pro-inflammatory factor NF-kB. In general, GR transrepression is the leading mechanism of glucocorticoid anti-inflammatory effects, while many adverse effects of glucocorticoids are driven by GR transactivation.

Our laboratory has been involved in delineation of mechanisms underlying side effects of glucocorticoids in skin. Using GRdim knockin mice characterized by impaired GR dimerization and activation, we found that GR transactivation plays an important role in skin atrophy. These data suggested that non-steroidal selective GR activators (SEGRA) that do not support GR dimerization, could preserve therapeutic potential of classical glucocorticoids but have reduced adverse effects in skin.  We are testing effects of the novel SEGRA called Compound A– a synthetic analog of natural aziridine precursor from African bush Salsola Botch in skin. We have also established anti-cancer GR-dependent activity of Compound A in epithelial and lymphoma cells.

Using knockout mice for the major GR target genes including Fkbp5 (GR chaperone) and DDIT4/REDD1 (one of the major negative regulators  of mTORC), we discovered that blockage of Fkbp5 and REDD1 significantly changes GR function and greatly protects skin against glucocorticoid-induced atrophy. This suggests a novel GR-targeted anti-inflammatory therapy where glucocorticoids are combined with inhibitors of GR target genes.

For more information, please see Dr. Budunova’s faculty profile.

Publications

See Dr. Budunova's publications in PubMed.

Contact Budunova Lab

Contact the Budunova Lab at 312-503-4669 or visit in the Montgomery Ward Building, 303 E. Chicago Avenue, Ward 9-015, Chicago, IL 60611

Faculty

Irina Budunova, MD, PhD

Research Associates

Pankaj Bhalla, PhDGleb Baida, PhDAnna Klopot, PhD

 Paul Burridge Lab

Investigating the application of human induced pluripotent stem cells to study the pharmacogenomics of chemotherapy off-target toxicity and efficacy

Research Description

The Burridge lab studies the role of the genome in influencing drug responses, known as pharmacogenomics or personalized medicine. Our major model is human induced pluripotent stem cells (hiPSC), generated from patient's blood or skin. We use a combination of next generation sequencing, automation and robotics, high-throughput drug screening, high-content imaging, tissue engineering, electrophysiological and physiological testing to better understand the mechanisms of drug response and action.

Our major effort has been related to patient-specific responses to chemotherapy agents. We ask the question: what is the genetic reason why some patients have a minimal side effects to their cancer treatment, whilst others have encounter highly detrimental side-effects? These side-effects  can include cardiomyopathy (heart failure or arrhythmias), peripheral neuropathy,  or hepatotoxicity (liver failure). It is our aim to add to risk-based screening by functionally validating genetic changes that predispose a patient to a specific drug response.

Recent Findings

  • Human induced pluripotent stem cells predict breast cancer patients’ predilection to doxorubicin-induced cardiotoxicity
  • Chemically defined generation of human cardiomyocytes

Current Projects

  • Modeling the role of the genome in doxorubicin-induced cardiotoxicity using hiPSC
  • Investigating the pharmacogenomics of tyrosine kinase inhibitor cardiotoxicity
  • hiPSC reprogramming, culture and differentiation techniques
  • High-throughput and high-content methodologies in hiPSC-based screening

For lab information and more, see Dr. Burridge’s faculty profile and lab website.

Publications

See Dr. Burridge's publications on PubMed.

Contact

Contact Dr. Burridge at 312-503-4895.

Lab Staff

Postdoctoral Fellows

Malorie Blancard, Hananeh Fonoudi, Mariam Jouni, Davi Leite, Tarek Mohamed, Disheet Shah

Graduate Students

Liora Altman-Sagan, Raymond Copley, K. Ashley Fetterman, Phillip Freeman, Donald McKenna, Emily Pinheiro, Marisol Tejeda, Carly Weddle

Technical Staff

Ali Negahi Shirazi

 Debabrata Chakravarti Lab

Epigenome and 3D chromatin organization dysregulations define human cancers and reproductive diseases

Research Description

Dr. Chakravarti’s research is focused on understanding epigenetic and transcriptional regulation of human tumorigenesis.  One of his research projects is focused on understanding the mechanisms that drive the development of uterine fibroids and endometriosis that affect an alarmingly high number of all women.  In another project, Dr. Chakravarti’s research team investigates molecular underpinning of contribution of transcription factors, cofactors and epigenomic and 3D genome reorganization regulation of prostate Cancer that affects a large number of men worldwide.  In a third project the laboratory determines the role of protein cofactors in regulation of cell cycle genes. Thus, our work interfaces both fundamental and translational research on diseases that affect humankind.  It is our hope that when combined with results from others, our research will contribute to the development of future therapeutics.  Dr. Chakravarti gratefully acknowledges continuous funding support from the NIH and key roles of his lab members and collaborators in the overall success of the Chakravarti Laboratory.

Dr. Chakravarti also enjoys teaching.  He has continuously taught both medical and graduate students.  He serves on numerous Ph.D thesis committees.  He has trained a large number of graduate students and postdoctoral fellows some of whom are now independent investigators at this and other institutions.

For more information, please see, visit the Dr. Chakravarti's faculty profile.

Publications

See Dr. Chakravarti's publications in PubMed.
Associate Editor: Endocrinology 2017-present; Editorial Board:  Molecular Endocrinology 2011- present, Mol. Cell. Biol. 2014-present
The Editor of a Book volume on “Regulatory Mechanisms in Transcriptional Signaling” in Progress in Molecular Biology and Translational Science (Vol 87), published in Aug 2009, Academic Press, Chakravarti, D. Editor

Contact Us

Dr. Chakravarti

312-503-1641

 Anis Contractor Lab

Seeking to understand the link between synaptic dysfunction and neuropsychiatric disorders and neurodevelopmental disorders

Research Description

Research in our laboratory is directed at understanding the mechanisms of synaptic transmission and plasticity and the role that glutamate receptors have in brain function and pathology. We use a multidisciplinary approach including in vitro electrophysiological recording, optogenetics, cellular imaging, mouse behavior and biochemical techniques. We ultimately seek to understand the link between synaptic dysfunction and neuropsychiatric disorders and neurodevelopmental disorders. Current projects are investigating altered synaptic signaling in mouse models of obsessive compulsive disorder, schizophrenia and fragile X syndrome.

For lab information and more, see Dr. Contractor's faculty profile or lab website.

Publications

See Dr. Contractor's publications on PubMed.

Contact

Contact Dr. Contractor 312-503-1843 or the lab at 312-503-0276.

Lab Staff

Research Faculty

John Armstrong, Jian Xu

Postdoctoral Fellows

Charlotte Castillon, Morgane Chiesa, Sara Colomer, Qionger He, John Marshall, Toshihiro Nomura, Shintaro Otsuka, Christine Remmers

Graduate Students

Olga Melendez-Fernandez, Chad Morton, Yiwen Zhu

Technical Staff

Damonick Baxter

Temporary Staff

Stephen Kraniotis

 Richard D'Aquila Lab

Pathogenesis of human immunodeficiency virus (HIV)

Research Description

The D’Aquila laboratory studies the pathogenesis of human immunodeficiency virus (HIV) persistence/latency and mechanisms of host “intrinsic” immune control of HIV replication. The long-term goal is to develop innovative strategies for a “functional cure” of HIV. We are developing novel interventions to induce sustained remissions after defined-duration antiretroviral therapy (ART). This includes bench-to-bedside research to characterize / leverage / increase APOBEC3 (A3) “intrinsic” immune defenses against HIV, diminish T cell activation-fueled HIV replication and innovate strategies to minimize latency/persistence of HIV.

In papers published in recent years, the D’Aquila laboratory proved that APOBEC3G and F are active in producer and target cells against wild-type (Vif-positive) HIV-1 at higher physiological levels of expression. Evidence was published that higher levels of A3G protein and activity contribute to the multiple mechanisms of spontaneous control of HIV-1 without ART seen in rare “elite controllers”. The laboratory has also identified that limiting c-Myc-dependent effects of the host T cell activation process limits early HIV replication in a way that may augment current virus-specific ART agents.

For more information, please see Dr. D'Aquila's faculty profile.

Publications

See Dr. D’Aquila's publications in PubMed.

Contact

Email Dr. D’Aquila

Phone 312/695-5085

 Paul DeCaen Lab

Studying ion channel relevance in cell biology and disease progression

Research Description

We study the biophysics, pharmacology and physiology of ion channels. Currently, we are focused on two divergent groups: voltage gated sodium channels (Nav) and Polycystin channels (also called Polycystic Kidney Disease Proteins, PKDs). Aside from these foci, we actively explore novel ion channels found in prokaryotic and eukaryotic cells with the goal of understanding their function in cell physiology.

Current Projects

Voltage Gated Sodium Channels

Navs conduct sodium ions into excitable cells like muscle and neurons, causing the cell membrane to depolarize on the microsecond time scale, a process essential for rapid communication in multicellular organisms. Potentially fatal conditions such as forms of epilepsy and cardiac arrhythmias arise when Navs are mutated.

With our collaborators, we continue to examine key questions:

  • How do these transmembrane proteins sense electrical potential and change from nonconductive to conductive states?
  • How do these transmembrane proteins select for sodium ions and not allow passage of the other ions present?     
  • What are the mechanisms of action of clinically relevant drugs (e.g. Valproate and Lamotrigine) and where are their receptor sites?

Polycystin Channels and Primary Cilia

Mutations in PKD1 and PKD2 are associated with Autosomal Dominant Kidney Disease (ADPKD). ADPKD is one of the most common monogenetic diseases in mankind, where progressive cyst formation results in kidney failure. Several members of the polycystins (PKD1, PKD1-L1, PKD2 and PKD2-L1) have been found in the primary cilia from cells of various tissues besides the kidney. The primary cilium is a solitary, small (5-15 mM in length) protuberance from the apical side of polarized cells.

With help from our collaborators, our research is directed to answer key questions:

  • How do ADPKD mutations alter PKD2 function? Do some mutations ‘turned on’ while others ‘turn off ’ the PKD2 channel?
  • How does PKD1/2 channel dysfunction result in cyst formation? Or conversely, what normal function do they serve for the primary cilium and how do PKDs maintain cell polarity?
  • What are the receptor sites within PKD2s that can modulation its ion channel function and are they drug-able?

For lab information and more, see Dr. DeCaen's faculty profile and lab website.

Publications

See Dr. DeCaen's publications on PubMed.

Contact

Contact Dr. DeCaen at 312-503-5930.

Lab Staff

Postdoctoral Fellows

My Chau Ta, Orhi Esarte Palomero, Megan McCollum

Visiting Scholar

Louise Vieira

Graduate Students

Eduardo Guadarrama, Megan Larmore

 Elizabeth Eklund Lab

The Eklund lab investigates myeloid leukemia and approaches to chemotherapy resistant disease.

Dr. Eklund’s laboratory studies are focused on understanding the molecular events that lead to development of myeloid leukemias (acute myeloid leukemia and chronic myeloid leukemia) and to the evolution of drug resistance in these diseases.  The goal is to identify potential molecular therapeutic targets that would delay or prevent drug resistance and relapse in AML and CML.  In related projects, the laboratory is investigating Fanconi Anemia, a genetic disease with defective DNA repair.  Patients with Fanconi Anemia frequently develop leukemia and provide a model for understanding the role of DNA repair in leukemogenesis.

Publications

View lab publications via PubMed.

For more information, visit the faculty profile page of Elizabeth Eklund, MD.

Contact Us

Contact Dr. Eklund at 312-503-3208 or the Eklund Lab at 312-503-3208.

Lab Staff

Ling Bei, MD
Research Associate
312-503-3206

Elizabeth Hjort
Graduate Student
312-503-4642

Liping Hu, PhD
Post Doctoral Fellow
312-503-4642

Weigi Huang, MD
Research Assistant Professor
312-503-3206

Chirag Shah, PhD
Research Associate
312-503-4642

Hao Wang, PhD
Research Assistant Professor
312-503-3204

 Jaime García-Añoveros Lab

Development, function, dysfunction and degeneration of sensory receptor cells and neurons

Research Description

We investigate sensory organs and particularly the uniquely specialized cells that detect external signals (the sensory receptor cells) and communicate this information to the brain (the primary sensory neurons). Our approach is to identify and characterize novel genes involved in the formation (during development or regeneration), function (as sensory transducers), dysfunction and death (causing diseases like deafness or neuropathic pain) of these cells. The genes we have studied so far encode ion channels (of the Deg/ENaC and TRP families) and transcriptional regulators (zinc-finger proteins; these studied in collaboration with Anne Duggan). We are interested in all forms of sensation but, as of now, have primarily explored the somatic (touch and pain), auditory and nasal sensory organs.

Sensory Neuron Development: We found Insm1, a zinc-finger gene regulator that determines the number of olfactory receptor neurons. Insm1 is expressed in the olfactory epithelium, as it is everywhere else in the developing nervous system, in late (but not early) progenitors and nascent (but not mature) neurons. It functions by promoting the transition of neuroepithelial progenitors from apical, proliferative and uncommitted (i.e., neural stem cells) to basal, terminally dividing and neuron-producing (Duggan et al., 2008; Rosenbaum, Duggan & García-Añoveros 2011). We are currently determining the role of Insm1 in other sensory organs, as well as elucidating the role of other novel neurodevelopmental genes.

Sensory Transduction: We pioneered a molecular model of how certain neurons can detect touch using DEG/ENaC channels and structural components of the extracellular matrix and the cytoskeleton (García-Añoveros et al., 1995; 1996), characterized a major pain transduction channel (TRPA1; Nagata et al., 2005), and continue searching for sensory transducers, particularly ion channels.

Sensory Neuron Degeneration: We found a form of cell death caused by mutations on ion channels that leave them open, generating lethal currents (García-Añoveros et al., 1998). In this way, we found how dominant mutations in the Mcoln3 (Trpml3) gene cause loss of mechanosensory cells of the inner ear and deafness (Nagata et al., 2008; Castiglioni et al., 2011). We continue exploring he role of TRPML3 and other ion channel in inner ear function and disease.

For more information, view the faculty profile of Jaime García-Añoveros, PhD or visit the Añoveros & Duggan lab site.

Publications

See Dr. García-Añoveros' publications on PubMed.

Staff Listing

Graduate Students

Chuan Foo
Teerawat Wiwatpanit

Post-doctoral Fellows

Research Assistant Professor

Technical Staff

Contact Info

Dr. García-Añoveros

Lab Phone: 312-503-4246
Office Phone: 312-503-4245

 Al George Lab

Investigating the structure, function, pharmacology and molecular genetics of ion channels and channelopathies

George Lab

Research Description

Ion channels are ubiquitous membrane proteins that serve a variety of important physiological functions, provide targets for many types of pharmacological agents and are encoded by genes that can be the basis for inherited diseases affecting the heart, skeletal muscle and nervous system.

Dr. George's research program is focused on the structure, function, pharmacology and molecular genetics of ion channels. He is an internationally recognized leader in the field of channelopathies based on his important discoveries on inherited muscle disorders (periodic paralysis, myotonia), inherited cardiac arrhythmias (congenital long-QT syndrome) and genetic epilepsies. Dr. George’s laboratory was first to determine the functional consequences of a human cardiac sodium channel mutation associated with an inherited cardiac arrhythmia. His group has elucidated the functional and molecular consequences of several brain sodium channel mutations that cause various familial epilepsies and an inherited form of migraine. These finding have motivated pharmacological studies designed to find compounds that suppress aberrant functional behaviors caused by mutations.

Recent Findings

  • Discovery of novel, de novo mutations in human calmodulin genes responsible for early onset, life threatening cardiac arrhythmias in infants and elucidation of the biochemical and physiological consequences of the mutations.
  • Demonstration that a novel sodium channel blocker capable of preferential inhibition of persistent sodium current has potent antiepileptic effects.
  • Elucidation of the biophysical mechanism responsible for G-protein activation of a human voltage-gated sodium channel (NaV1.9) involved in pain perception.

Current Projects

  • Investigating the functional and physiological consequences of human voltage-gated sodium channel mutations responsible for either congenital cardiac arrhythmias or epilepsy.
  • Evaluating the efficacy and pharmacology of novel sodium channel blockers in mouse models of human genetic epilepsies.
  • Implementing high throughput technologies for studying genetic variability in drug metabolism.
  • Implementing automated electrophysiology as a screening platform for ion channels.

For lab information and more, see Dr. George’s faculty profile.

Publications

See Dr. George's publications on PubMed.

Contact

Contact Dr. George at 312-503-4892.

Lab Staff

Research Faculty

Irawati Kandela, Thomas Lukas, Christopher Thompson, Carlos Vanoye

Senior Researchers

Reshma Desai, Jean-Marc DekeyserPaula FriedmanChristine Simmons

Lab Manager

Tatiana Abramova

Postdoctoral Fellows

Dina Simkin

Medical Residents

Scott Adney, Tracy Gertler

Graduate Students

Huey Dalton, Surobhi Ganguly, Adil WafaLisa Wren

Technical Staff

Nora Ghabra, Nirvani Jairam

 Xiaolin He Lab

Mechanisms of signal transmission across the membrane via the cell-surface receptors

Research Description

This laboratory is interested in cancer, neural development and reproduction-related structural mechanisms of how extracellular signals (e.g., growth factors, adhesion molecules and morphogens) are translated into intracellular signals by plasma membrane receptors. We use biophysical methods (crystallography, calorimetry, surface plasmon resonance, analytical ultracentrifugation, etc.) in combination with functional studies to define the physiological states and binding processes of these receptors and their complexes with ligands. Our research targets include receptor tyrosine kinases, Semaphorin and its receptors and leucine-rich-repeat-containing G-protein coupled-receptors.

For more information, visit the faculty profile of Xiaolin He, PhD.

Publications

See Dr. He's publications in PubMed.

Staff Listing

Research Associate:
Xiaoyan Chen

Graduate Student:
Po-Han Chen

Contact Us

Contact Dr. He at 312-503-8030 or the He Lab at 312-503-8029.

 Amy Heimberger Lab

Improving the lives of patients with central nervous system (CNS) cancers through the development of new immunotherapies informed by understanding the underlying unique immunobiology of the CNS. 

Research Description

Our laboratory studies the unique immunobiology of CNS tumors that informs our development of immuno-oncology therapeutics. The laboratory has been intricately involved in a wide variety of bench-to-bedside immune therapeutics, including those that developed in the laboratory and arising from our own patents. We work collaboratively with industry on their pipeline agents to clarify indications and companion biomarkers. The laboratory carries unique expertise in the investigational new drug process and window-of-opportunity clinical trials. The laboratory conducts extensive immune profiling of patient tumors including ex vivo functional assays. Our studies are directed to how various cells interact within the tumor microenvironment and the functional implications using multiplex imaging, methylation profiling, single cell sequencing and transcriptomic analysis. Areas in which we have contributed to science include the following:

EGFRvIII peptide vaccines Our laboratory co-developed with Duke University from bench-to-bedside a peptide (PEP-3-KLH/CDX-110) vaccine strategy that targets the epidermal growth factor receptor (EGFRvIII), that demonstrated induction of anti-tumor immune responses.

 STAT3 mediated immune suppression and therapeutic targeting We clarified that the signal transducer and activator of transcription 3 STAT3 pathway is a key molecular hub of gliomagenesis and tumor-mediated immune suppression and conducted the preclinical development of a novel small molecule inhibitor of STAT3, WP1066, for which I hold the IND. STAT3 has been considered an “un-druggable” target and this is a first-in-man agent with specificity to STAT3. This drug has been licensed to Moleculin and is now in clinical trials.

Glioblastoma mediated mechanisms of immune suppression We have demonstrated that glioblastoma subverts the immune system to become tumor protective, especially by 1) driving tumor-associated microglia/macrophages to assist in potentiating gliomagenesis; 2) by recruitment of Tregs; 3) and by the intrinsic properties of cancer stem cells which are immunosuppressive on both adaptive and innate immunity. This investigative direction has provided potential therapeutic targets/strategies and biomarker elucidation.

miRNA and nanoparticle therapeutics The laboratory has elucidated the role of epigenetic microRNA regulation on tumor-mediated immune suppression, with an emphasis on potential translational therapeutic approaches.  One of these strategies, miR-124 delivered with lipid nanoparticles to the immune compartment entered clinical trials in spontaneously arising gliomas in canines. 

Immune checkpoint therapeutics and response biomarkers Given the recent FDA approvals of immune checkpoint inhibitors for malignancies, there is great enthusiasm for their use in glioblastoma. Recent work in our lab has been focused on clarification of potential response biomarkers and identification of GBM patient subsets that may benefit.

For more information, please visit the Amy Heimberger Lab page

 

 Dai Horiuchi Lab

Understanding the cellular events that influence the aggressiveness of tumors and patient clinical outcome

Research Description

The major focus of the Horiuchi lab, established on April 1, 2015, is on the mechanisms of tumor maintenance and progression in breast cancer and to identify novel therapeutic targets and treatment strategies. To achieve these goals, we utilize a collection of human breast cancer cell lines, preclinical animal models and high-throughput screening approaches along with state-of-the-art bioinformatics through collaboration with experts in the field.

We are currently focused on the following areas:

  1. Mechanisms of tumor maintenance and progression medicated by proto-oncogenes (i.e., MYC transcription factor, PIM family of serine/threonine kinases, etc.), their activators and effectors and the tumor microenvironment.
  2. Biology and therapeutic targetability of novel molecular factors that determine patient clinical outcome.

For lab information and more, see Dr. Horiuchi’s faculty profile.

Publications

See Dr. Horiuchi's publications on PubMed.

Contact

Contact Dr. Horiuchi at 312-503-4085 or the lab at 312-503-4349.

Lab Staff

Technical Staff

Lauren Begg, Adrienne Orriols

 Zhe Ji Lab

Dissecting the regulation of gene transcription and RNA translation underlying oncogenic processes.

Research Description

Cancer happens through accumulated genetic mutations and epigenetic alternation in normal cells. With the advances of genomic technologies, we now can precisely characterize the genome-wide alternations of gene expression underlying oncogenic processes in a cost-effective and unbiased manner. My lab will use the combined experimental genomic technologies and computational modeling to examine the regulation of gene transcription and RNA translation during steps of oncogenesis. We aim at revealing novel cancer therapeutic targets and strategies for precision medicine and immunotherapy.

Current Projects

Currently, we are working on the following projects.

  • Characterizing the transcriptional regulatory circuits mediating inflammation in the cancer microenvironment.
  • Examining the genome-wide regulation of RNA translation in cancers.
  • Defining the functional roles of non-canonical translation in lncRNAs, pseudogenes and 5’UTRs in cancers.

For lab information and more, see Dr. Ji's faculty profile.

Publications

See Dr. Ji's publications on PubMed.

Contact

Contact Dr. Ji at 312-503-2187.

Lab Staff

Postdoctoral Fellows

Qianru Li, Haiwang Yang

Graduate Students

Emily Stroup, Sheng Wang

 Jennifer Kearney Lab

Investigating the genetic basis of epilepsy

Research Description

My research program is focused on studying the genetic basis of epilepsy, a common neurological disorder that affects approximately 1% of the population. Epilepsy is thought to have a genetic basis in approximately two-thirds of patients, including a small fraction caused by single gene mutations. Many genes responsible for rare, monogenic epilepsy have been identified. The genes identified are components of neuronal signaling, including voltage-gated ion channels, neurotransmitter receptors, ion-channel associated proteins and synaptic proteins. We use mouse models with mutations in ion channel genes to understand the underlying molecular basis of epilepsy and to identify modifier genes that influence phenotype severity by modifying disease risk. Identifying genes that influence epilepsy risk improves our understanding of the underlying pathophysiology and suggests novel targets for therapeutic intervention.

For lab information and more, see Dr. Kearney's faculty profile.

Publications

See Dr. Kearney's publications on PubMed.

Contact

Contact Dr. Kearney at 312-503-4894.

Lab Staff

Research Faculty

Nicole Hawkins, Thuy Vien

Graduate Students

Erin Baker, Letonia Copeland-Hardin, Dennis Echevarria, Seok Kyu Kang

Technical Staff

Conor Dixon

 Shana Kelley Lab
New Technologies for Disease Biology

Research Description

The Kelley lab utilizes an interdisciplinary approach that integrates nanoscience, bioanalytical science and engineering, focusing on high-throughput single-cell profiling and the application of new technology platforms of the characterization of pathways relevant to cancer progression and treatment.

 

 Julie Kim Lab

The role of progesterone receptor in uterine diseases

Research Description

Progesterone is essential for the regulation of normal female reproductive function.  Its mode of action is diverse and dependent on the target tissues.  In my lab we are interested in delineating the molecular mechanisms of progesterone action through its receptor, PR in the uterus.  This is done in the context of normal endometrial differentiation, specifically, decidualization, as well as in uterine pathologies, such as endometriosis, endometrial cancer and uterine fibroids.  Interestingly, in these three diseases, progesterone responsiveness is aberrant.

Endometrial cancer is the most common gynecologic cancer diagnosed in the United States with an estimated 40,100 new cases and about 7,500 deaths in 2008.  As risk factors for endometrial cancer increase, the incidence of this disease will also rise, with a paradigm shift to younger ages. In our laboratory, we investigate the role of progesterone receptor in endometrial cancer to understand why progestin therapy is not an effective treatment in all cases of endometrial cancer.

Endometriosis is an estrogen-dependent disorder affecting up to 10% of the female population and 30-50% of infertile women, with no cure and limited therapies. It is often associated with debilitating pelvic pain and infertility. This disease has also been referred to as a “progesterone resistant” disease since the ectopic and eutopic tissues do not respond to progesterone as it does in normal endometrial tissues. Our laboratory is investigating progesterone resistance in endometriosis and identifying specific biological targets for the future development of alternative therapies.

Leiomyoma, also known as uterine fibroids, are benign tumors originating from the myometrium. These tumors can range from a few millimeters to over 20 cm in size. Leiomyomas are common and can occur in up to 77% of women while up to 20% of women suffer from significant morbidity, pain and discomfort and excessive menstrual bleeding. Leiomyomas are the primary indication for over 200,000 hysterectomies in the United States. In our laboratory we are investigating how progesterone promotes growth of leiomyomas by focusing on the non-genomic signaling of progesterone on the PI3K/AKT pathway. These studies are translated to the identification of important signaling molecules that can be targeted using small molecule inhibitors.

For more information, please see Dr. Kim's faculty profile or the Kim Lab website.

Publications

See Dr. Kim's publications in PubMed.

Contact

Contact Dr. Kim at 312-503-5377 or the Kim Lab at 312-503-4762.

 David Klumpp Lab

Molecular Mechanisms Of Bladder Inflammation and Pelvic Pain

Research Description

Our laboratory employs state-of-the-art cell culture and animal models to pursue multi-disciplinary projects in bacterial pathogenesis and neuro-immune interactions in a crippling pain syndrome.  A key to our success is the rich training environment resulting from the close collaboration between clinical and basic scientists.

Urinary tract infection (UTI) is both a major medical issue and a fascinating problem of bacterial pathogenesis.  We investigate all aspects of host pathogen interactions, from the immediate biochemical signaling evoked in bladder cells, to the associated inflammation, to the development of adaptive immune responses.  We recently identified a novel signaling response of bladder cells induced by binding of uropathogenic E. coli (UPEC) that mediates the mutually exclusive processes of epithelial cell apoptosis and bacterial invasion of bladder epithelial cells; how this occurs is an active area of study.  We have also identified a candidate live-attenuated UTI vaccine based on a UPEC mutant.  We find that the UPEC mutant vaccine induces protective responses 100-fold greater than wild type UPEC.  We are now determining the mechanism of this enhanced response by testing the hypothesis that the UPEC mutant skews the normal immune response and thus generates a more effective immunity.

Although pelvic pain can result from acute infection, interstitial cystitis (IC) is a debilitating chronic pelvic pain syndrome of unknown origin that is often considered a chronic bladder inflammation. We utilize a herpesvirus to induce an IC-like condition in mice  Using this model, we have identified the mechanisms that result in both bladder pathophysiology and pelvic pain. Interestingly, while both pain and bladder damage require mast cell activation, pelvic pain results from the release of mast cell histamine, whereas bladder pathology is driven by mast cell release of tumor necrosis alpha (TNF). Current studies include the genetic basis of pain susceptibility, the spinal regulation of histamine and TNF release and the viral basis of pain. In addition, we recently were awarded a prestigious NIH center grant to study pelvic pain syndromes. The center award will extend our bladder pelvic pain studies to prostate- and bowel-associated pelvic pain and determine the mechanisms of pelvic organ crosstalk and signal integration in the spinal cord in mice. Our center collaborators will examine cortical and cognitive changes in pelvic pain patients using a combination of functional MRI and behavioral tests and develop novel quality-of-life tests to characterize pelvic pain non-invasively within populations. Thus, this center will illuminate pelvic pain mechanisms in clinical, epidemiologic and basic animal studies.

For more information, visit Dr. Klumpp's faculty profile.

Publications

See Dr. Klumpp's publications in PubMed.

Contact

Dr. Klumpp

 Krainc Lab

Dr. Krainc’s lab studies the mechanisms of neuronal dysfunction in neurodegenerative disorders that affect children and adults.

Research Description

The overarching goal of my laboratory is to study rare diseases such Huntington’s and genetic forms of Parkinson’s disease, as a window to understanding neurodegeneration across the lifespan. More recently, we have focused on rare lysosomal diseases such as Gaucher’s in order to identify specific targets and mechanisms that contribute to neurodegeneration in Parkinson’s and related synucleinopathies. It is expected that such defined targets will facilitate mechanism-based development of targeted therapies for children with neuronopathis Gaucher’s disease as well as adult-onset synucleinopathies such as Parkinson’s disease. To validate and study these targets and novel therapies in human neurons, we have utilized induced pluripotent stem cells (iPS) generated by reprogramming of patient-specific skin fibroblasts. These iPS cells are differentiated into specific neuronal subtypes in order to characterize the contribution of genetic, epigenetic and environmental factors to disease mechanisms and to test novel therapeutic approaches.

For more information see the faculty profile of Dimitri Krainc or visit the Krainc Lab website.

Recent Publications

View Dr. Krainc's full list of publications in PubMed.

Contact information

Dimitri Krainc, MD, PhD
Ward Professor and Chairman
312-503-3936

 Xiao-Nan Li Lab

Understanding tumor biology and implementing preclinical drug testing of malignant brain tumors

Research Description

Our research work focuses on molecular neuro-oncology and experimental therapeutics of malignant brain tumors.  Our goal is to develop more effective and less toxic therapies for children with malignant brain tumors to significantly improve the clinical outcomes.  1) Clinically relevant and molecularly accurate animal models: We have optimized a protocol for to implant a patient’s tumor cells directly into the matched location in mouse brains.  Our laboratory has developed >130 patient derived orthotopic xenograft (PDOX or orthotopic PDX) models of pediatric brain tumors, including high-grade glioma/glioblastoma (GBM), medulloblastoma (MB), ependymoma (EPN), diffuse intrinsic pontine glioma (DIPG), atypical teratoid/rhabdoid tumor (ATRT), Embryonal tumors with multilayered rosettes (ETMR), CNS germinoma, and pleomorphic xanthoastrocytoma (PXA), as well as ~20 models of adult GBM and meningioma. 2) All the models are subjected to detailed histopathological and comprehensive molecular characterizations through global gene expression (RNAseq, single cell RNAseq), whole genome sequencing, DNA copy number analysis, whole genome DNA methylation analysis during serial in vivo subtransplantations to confirm thee cellular and molecular fidelities of the patient-specific PDOX models.  3) Recognizing the need of in vitro model system, we are also utilizing our PDOX model system to develop long term cultures/cell lines as monolayer, 3D neurospheres and organoids. 4) Using this unique in vitro and in vivo model system, we are actively engaged in the understanding of tumor biology and the testing of new therapeutic strategies.

Current Projects

  • Understanding the mechanisms of brain tumor invasion of pediatric GBM
  • Discovery of cellular and molecular drivers of medulloblastoma metastasis
  • Investigating the regulation of cell cycle progression, particularly from quiescent G0 to active G1 phase
  • Implementing unbiased high-throughput combinatory drug screening against highly malignant brain tumors using a novel drug library composed of 17,000 drugs and investigational agents
  • Identifying cellular origins and molecular drivers of therapy resistance and tumor relapse
  • Evaluating therapeutic efficacy and elucidation of mechanisms of action of novel anti-cancer therapies in vivo in PDOX models for the initiation of clinical trials.

For more information, visit the faculty profile of Xiao-Nan Li, MD, PhD.

Publications

See Dr. Li's publications.

Contact

Email Dr. Li

 Richard Longnecker Lab

Epstein-Barr virus (EBV) and herpes simplex virus (HSV) entry, replication and pathogenesis.

Research Description

Research in the Longnecker laboratory focuses on herpes simplex virus (HSV) and Epstein-Barr virus (EBV). These viruses typically cause self-limiting disease within the human population but both can be associated with serious complications. EBV is associated with variety of hematopoietic cancers such as African Burkitt lymphoma, Hodgkin Lymphoma and adult T-cell leukemia. EBV-associated lymphoproliferative disease occurs in individuals with congenital or acquired cellular immune deficiencies. The two notable epithelial diseases associated with EBV infection are nasopharyngeal cancer and oral hairy leukoplakia. Similar to EBV, HSV latent infections are very common in humans. HSV typically does not cause severe disease but is associated with localized mucocutaneous lesions, but in some cases can cause meningitis and encephalitis. The Longnecker laboratory focuses on several aspects of EBV and HSV replication and pathogenesis. First, the molecular basis EBV transformation and how it relates to cancer is being investigated. The laboratory is currently screening selective inhibitors that may be beneficial in EBV-associated cancers such as Hodgkin lymphoma, Burkitt lymphoma and proliferative disorders that occur in HIV/AIDS and transplant patients. Second, the laboratory is investigating herpesvirus latency in the human host and pathogenesis associated with infections in humans. In this regard, the laboratory is developing animal models for EBV and HSV infections. Finally, the laboratory is investigating the function of herpesvirus encoded proteins and the cellular receptors that are important for infection both using in vivo culture models as well as animal models. Ultimately, studies by the Longnecker laboratory may provide insight for the development of novel therapeutics for the treatment of herpesvirus infections in humans and better understanding of the herpesvirus life cycle in the human host

For lab information and more, see Dr. Longnecker's faculty profile.

Publications

See Dr. Longnecker's publications on PubMed.

Contact

Contact Dr. Longnecker at 312-503-0467 or the lab at 312-503-0468 or 312-503-9783.

Lab Staff

Research Faculty

Jia Chen, Qing Fan, Kamonwan "Pear" Fish, Masato Ikeda

Adjunct Faculty

Sarah Connolly, Michelle Swanson-Mungerson

Graduate Students

Cooper Hayes, Daniel Giraldo Perez, Seo Jin Park

Technical Staff

Sarah Kopp, Rachel Riccio, Samantha Schaller, Nanette Susmarski

 Yong-Chao Ma Lab

Regulation of Motor Neuron and Dopaminergic Neuron Function in Development and Disease

Postdoctoral fellow jobs and graduate student rotation projects are available.

Research Description

Spinal Motor Neurons and Spinal Muscular Atrophy (SMA)

SMA is characterized by the selective degeneration of spinal motor neurons. As the leading genetic cause of infant mortality, SMA affects one in every eight thousand live births. Our group is interested in studying mechanism regulating motor neuron development and function, as well as why motor neurons specifically degenerate in SMA. To address these questions, we use a combination of genetic, biochemical and cell biological approaches and utilize genetically modified mice, induced pluripotent stem (iPS) cells reprogrammed from fibroblasts and zebrafish as model systems. We focus on the regulation of mitochondrial functions in SMA pathogenesis. Based on our findings, we hope to develop new therapeutic strategies for treating SMA.

 
Dopaminergic Neurons and Parkinson's Disease

Dopaminergic neurons located in the ventral midbrain control movement, emotional behavior and reward mechanisms. Dysfunction of these neurons is implicated in Parkinson’s disease, drug addiction, depression and schizophrenia. Our group is interested in the genetic and epigenetic mechanisms regulating dopaminergic neuron functions in disease and aging conditions. We are particularly interested in how aging and mitochondrial oxidative stress contribute to dopaminergic neuron degeneration in Parkinson's disease through transcriptional and epigenetic regulations. We use mouse models, cultured neurons and iPS cells for these studies.

For more information visit Dr. Ma's faculty profile and Dr. Ma's lab website within the Children's Hospital Research Center.

Publications

View Dr. Ma's publications at PubMed

Contact

Email Dr. Ma

Phone 773-755-6339

Lab Staff

Nimrod Miller, PhD, Postdoctoral Fellow

Han Shi, Graduate Student

Brittany Edens, Graduate Student

Kevin Park, Graduate Student

Monica Yang, Undergraduate Student

Aaron Zelikovich, Undergraduate Student

 Daniela Matei Lab

Mechanisms of ovarian cancer metastasis and novel therapeutics for ovarian cancer

Research Description

My laboratory studies mechanisms of ovarian cancer metastasis and novel therapeutics for ovarian cancer. The general theme is translation between bench and clinic; with laboratory research forming the foundation for clinical experiments. 

One direction of investigation relates to the interaction between cancer cells and the peritoneal stroma.  We described the functions of tissue transglutaminase as an interacting partner of b-integrins and regulator of peritoneal metastasis.  Based on new mechanistic insight into the roles of this enzyme in ovarian cancer, we discovered and began characterizing new small molecule inhibitors for the transglutaminase-fibronectin-integrin interaction that are being developed as anti-cancer agents. We are studying these new inhibitors in-vitro and in in-vivo models of ovarian cancer metastasis.

Another area of research focusses on the characteristics and therapeutic vulnerabilities of ovarian cancer stem cells.  We used small molecule inhibitors that target ALDH1A1 to block the tumorigenic capacity of these cancer-initiating cells.  We are studying how ALDH1A1 inhibitors alter stem cell specific signaling and how ALDH1A1 is involved in maintaining the cancer stem cell properties. 

More recently we identified new metabolic alterations involving fatty acids desaturation in cancer stem cells.  We have targeted lipid metabolism using small molecule inhibitors and are studying the mechanisms by which these metabolic changes contribute to the maintenance and tumorigenicity of cancer stem cells.  Future goals are to refine the use of ALDH and fatty acid desaturases inhibitors to target cancer stem cells residual after chemotherapy and to eradicate the disease.

Another important direction of investigation is epigenetic modulation as a method of resensitization to platinum in ovarian cancer.  We successfully brought to the clinic the concept that epigenetic modulation re-sensitizes chemotherapy-resistant ovarian tumors to carboplatin.  I led a randomized multi-institutional clinical trial testing the effects of DNA hypomethylating agents and carboplatin compared to standard chemotherapy.  We are now analyzing the genome and epigenome of platinum resistant ovarian cancer using specimens from this trial.  We have identified several pathways that are associated with platinum resistance and respond to hypomethylating agents.  We have designed a new strategy to target pathway-specific DNA methylation and are testing the effects of this intervention on cell signaling and gene expression profiles in ovarian cancer cells.  

Publications

View Dr. Matei's publications on PubMed

Contact

Email Dr. Matei

Phone 312 503-4853

 Marc Mendillo Lab

Cellular stress response systems in malignancies

Research Description

The cellular stress response systems guard the proteome from diverse endogenous and environmental insults to maintain the fitness of the organism. Ironically, this pro-survival system can act to the detriment of the host to enable tumor cells accommodate to the myriad stresses associated with malignancy. Our long-term goals are to identify and characterize the systems that promote protein homeostasis, understand how these systems are co-opted and perturbed in malignancy, and ultimately identify means to manipulate them for therapeutic benefit. To accomplish these goals our group bridges biochemical, genetic and chemical biology approaches with systematic high-throughput and genomic methods.

For lab information, publications and more, see Dr. Mendillo’s faculty profile.

Publications

View Dr. Mendillo's publications at PubMed

Contact

Email Dr. Mendillo

Phone 312-503-5685

 Richard Miller Lab

Studying molecular aspects of nerve cell communication and neurodegenerative disease

Miller Lab Transgenic Reporter Mice

Co-localization of Nestin and GFAP in the DG of Nestin-EGFP Transgenic Reporter Mice

Research Description

The laboratory led by Richard Miller, PhD, is interested in studying molecular aspects of nerve cell communication. One of our major interests has been to understand the structure and function of calcium channels. The influx of Ca into neurons through these channels is important for many reasons, including the release of neurotransmitters. We have identified a family of molecules that act as Ca channels in neurons and other types of cells. Each of these molecules has slightly different properties that underlie different neuronal functions. We have analyzed the properties of these molecules by examining their electrophysiological properties following their expression in heterologous expression systems and imaging techniques. Furthermore, we have generated calcium channel knockout mice that have interesting properties such as altered pain thresholds, seizures and memory deficits. We have also been interested in how Ca channels can be regulated by the activation of Gprotein coupled receptors. We have been analyzing the interaction of Gprotein subunits with Ca channels using FRET imaging and other techniques.

Other projects in our laboratory are aim to understanding the molecular basis of neurodegenerative disease. We study Alzheimer's disease, Amyotrophic lateral sclerosis (Lou Gehrig's disease), HIV-1 related dementia and other neuropathological conditions. In the case of HIV-1 infection, we have been examining the properties and functions of HIV-1 receptors on neurons. These receptors are known to be receptors for chemokines -small proteins that are known to direct the functions of the immune system. We have shown that neurons express many types of chemokine receptors and that activation of these receptors can produce both short and long term effects on neurons. Activation of chemokine receptors expressed by sensory neurons produces neuronal excitation and pain. Activation of chemokine receptors on hippocampal neurons has a prosurvival effect, whereas binding of HIV-1 to these receptors induces apoptosis. We are studying the molecular mechanisms that produce this diverse effects with a view to understanding the molecular basis for HIV-1 related dementias.

For lab information and more, see Dr. Miller’s faculty profile.

See Dr. Miller’s blog “The Keys to all Mythologies: Science, Medicine and Magic” to read articles concerning scientific topics of current interest as well as historical accounts of scientific issues.

Publications

See Dr. Miller's publications on PubMed.

Contact

Contact Dr. Miller at 312-503-3211.

Lab Staff

Research Faculty

Abdelhak Belmadani

Postdoctoral Fellow

Dongjun Ren

Graduate Students

Brittany Hopkins

 Stephen Miller Lab

Elucidation of mechanisms of pathogenesis and immune regulation of autoimmune disease, allergy and tissue/organ transplantation

Research Description

The laboratory is interested in understanding the mechanisms underlying the pathogenesis and immunoregulation of T cell-mediated autoimmune diseases, allergic disease and rejection of tissue and organ transplants.  In particular, we are studying the therapeutic use of short-term administration of costimulatory molecule agonists/antagonists and specific immune tolerance induced by infusion of antigen-coupled apoptotic cells and PLG nanoparticles for the treatment of animal models of multiple sclerosis and type 1 diabetes, allergic airway disease, as well as using tolerance for specific prevention of rejection of allogeneic and xenogeneic tissue and organ transplants.

For lab information and more, see Dr. Miller's faculty profile.

Publications

See Dr. Miller's publications on PubMed.

Contact

Contact Dr. Miller at 312-503-7674 or the lab at 312-503-1449.

Lab Staff

Research Faculty

Igal IferganJoseph Podojil, Dan Xu

Adjunct Faculty

John Galvin

Postdoctoral Fellows

Andrew Cogswell, Gabriel Lorca, Tobias Neef, Haley Titus

Lab Manager

Sara Beddow

Technical Staff

Ming-Yi Chiang, Lindsay Moore

Visiting Scholars

Michael Boyne, Daniel Getts

Temporary Staff

Grant Primer

 Hidayatullah G. Munshi Lab

The Munshi lab is interested in the role of fibro-inflammatory stromal reaction in pancreatic cancer progression.

The Munshi Lab is focused on understanding the role of the key collagenase MT1-MMP (MMP-14) and members of the Snail family transcription factors in pancreatic cancer progression using transgenic mouse models. We are also interested in understanding how the pronounced fibrotic reaction induces epigenetic changes to contribute to chemotherapy resistance. We have shown that the collagen microenvironment induces histone acetylation and that targeting 'readers' of histone acetylation marks using BET inhibitors can limit growth of pancreatic cancer cells. We plan to evaluate the efficacy of BET inhibitors in our mouse models with the eventual goal of testing this class of inhibitors in patients with pancreatic cancer.

Publications

View lab publications via PubMed.

For more information, visit the faculty profile page of Hidayatullah G Munshi, MD.

Contact Us

Contact Dr. Munshi at 312-695-6180 or the Munshi Lab at 312-503-0312.

Lab Staff

Christina Chow
Post Doctoral Fellow
312-503-0312

Holly Hattaway
Research Technician
312-503-0312

Krishan Kumar
Senior Research Associate
312-503-0312

 Ozdinler Lab

Dr. Ozdinler’s lab studies the cortical component of motor neuron circuitry degeneration in amyotrophic lateral sclerosis (ALS) and other related disorders.

Research Description

We are interested in the cellular and molecular mechanisms that are responsible for selective neuronal vulnerability and degeneration in motor neuron diseases. Our laboratory especially focuses on the corticospinal motor neurons (CSMN) which are unique in their ability to collect, integrate, translate and transmit cerebral cortex's input toward spinal cord targets. Their degeneration leads to numerous motor neuron diseases, including amyotrophic lateral sclerosis, hereditary spastic paraplegia and primary lateral sclerosis.

Investigation of CSMN require their visualization and cellular analysis. We therefore, generated reporter lines in which upper motor neurons are intrinsically labeled with eGFP expression. We also characterized progressive CSMN degeneration in various mouse models of motor neuron diseases and continue to generate reporter lines of disease models, in which the upper motor neurons express eGFP.

The overall goal in our investigation, is to develop effective treatment strategies for ALS and other related motor neuron diseases. We appreciate the complexity of the disease and try to focus the problem from three different angles. In one set of studies, we try to reveal the intrinsic factors that could contribute to CSMN vulnerability by investigating the expression profile of more than 40,000 genes and their splice variations at different stages of the disease. In another set of studies, we try to understand the role of non-neuronal cells on motor neuron vulnerability and degeneration, using a triple transgenic mouse model, in which the cells that initiate innate immunity are genetically labeled with fluorescence in an ALS mouse model. These studies will not only reveal the genes that show alternative splice variations, but also inform us on the canonical pathway and networks that are altered with respect to disease initiation and progression.

Even though the above mentioned studies, which use pure populations of neurons and cells isolated by FACS mediated approaches, will reveal the potential mechanisms that are important for CSMN vulnerability, it is important to develop therapeutic interventions. One of the approach we develop is the AAV-mediated gene delivery directly into the CSMN via retrograde transduction. Currently, we are trying to improve CSMN transduction upon direct cortex injection.

Identification of compounds that support CSMN survival is an important component of pre-clinical testing. We develop both in vitro and in vivo compound screening and verification platforms that inform us on the efficiency of compounds for the improvement of CSMN survival.

In summary, we generate new tools and reagents to study the biology of CSMN and to investigate both the intrinsic and extrinsic factors that contribute to their vulnerability and progressive degeneration. We develop compound screening and verification platforms to test their potency on CSMN and develop AAV-mediated gene delivery approaches. Our research will help understand the cellular basis of CSMN degeneration and will help develop novel therapeutic approaches.

For more information see the faculty profile of Pembe Hande Ozdinler, PhD or the Ozdinler Lab website.

Visit the Les Turner ALS Center

Publications

View Dr. Ozdinler's full list of publications at PubMed.

Contact

Email Hande Ozdinler, PhD 

Phone: 312-503-2774

Twitter: @DrOzdinler

 Jones Parker Lab

Targeting neural substrates to improve treatment outcomes for neuropsychiatric diseases

Research Description

We use imaging approaches to acquire large-scale recordings of neural activity during behavior, focusing on deep-brain areas implicated in neurological and psychiatric diseases, such as striatum. We use these tools to delineate the functional contribution of neuronal sub-populations in these brain areas to normal behavior in control subjects and pathological behavior in models for brain diseases. Our aim is to target these neural substrates to improve treatment outcomes for neuropsychiatric diseases.

For lab information and more, see Dr. Parker's faculty profile and lab website.

Publications

See Dr. Parker's publications on PubMed.

Contact

Contact Dr. Parker at 312-503-3165.

Lab Staff

Postdoctoral Fellows

Kate Lanza, Ben Yang, Seongsik Yun

Graduate Student

Niki Moya

Technical Staff

Stefan Fleps, Madison Martin

 Minoli Perera Lab

Pharmacogenomics research in minority patient populations

Perera Lab

Research Description

The Perera laboratory focuses on pharmacogenomics (using a patient's genome to predict drug response) in minority populations. Working in this translation research space requires both clinical expertise as well as the use of high-throughput basic science approaches. Our goal is to bring the benefits of precision medicine to all US populations.

The Perera lab has recruited patient populations from around the world. The data collection includes genomic (DNA), transcriptomic (mRNA), pharmacokinetic and clinical data. We then integrate these different data sources to understand genetic drivers of drug response (e.g. genetic predictors of adverse events) as well as disease. By studying minority populations the lab has discovered genetic risk variants that may benefit the implementation of precision medicine in African Americans and others.

Recent Findings

  • Warfarin Bleeding Risk Association study
    We recently discovered a genetic variant that predispose African Americans to bleeding complications while on anticoagulant drugs. These bleeds occurred even when the patient was within the therapeutic window for the medication. We hope that this new data will help to identify high risk individuals prior to therapy.
  • Novel African-specific genetic polymorphisms predict the risk of venous thromboembolism
    We discovered a new genetic variant associated with a 2.5 fold increase in risk of developing a blood clot. We went on to show that this SNP significantly affects the expression of a key protein in the coagulation cascade. View article on PubMed.
  • Common genetic variant is predictive of warfarin metabolism and gene expression in African Americans
    We tested the association of a SNP, previously shown to effect gene expression CYP2C9, for association with warfarin drug clearance (pharmacokinetics). This SNP increased the expression of CYP2C9 (enzyme that metabolized warfarin), hence causing fast clearance of the drug. This African American-specific SNP may help to explain the higher warfarin dose required by African Americans in general. View article on PubMed.

Current Projects

  • Genomics of Drug Metabolism
    We are using African America primary hepatocytes to understand the genetic regulation of drug metabolizing enzymes that are involved in a majority of drug used in the US.
  • Anticoagulant Pharmacogenomics
    We are conducting several genetic association studies to understand both the genetic drivers and the biological mechanisms behind response and adverse effect to anticoagulant medications.
  • Pharmacogenomics of Inflammatory Bowel disease
    We are investigating the genetic predictors of primary non-response to biologic therapies used in inflammatory bowel disease. Studies have implication for other autoimmune disorders that target the same pathways.
  • eMERGE
    We are involved in analyzing the GWAS and sequencing data specifically for genomics variation affect key pharmacogenomics gene in African Americans.

For lab information and more, see Dr. Perera's faculty profile and lab website.

Publications

See Dr. Perera's publications on PubMed.

Contact

Contact Dr. Perera at 312-503-6188 or the lab at 312-503-4119.

Lab Staff

Lab Manager

Cristina Alarcon

Bioinformatics Analyst

Mrinal Mishra 

Postdoctoral Fellows

Paula Friedman, Guang Yang

Graduate Student

Carolina Clark

Temporary Staff

Danika Balas

 Leonidas Platanias Lab

Dr. Platanias’ research laboratory focuses on understanding the signaling pathways in different types of cancers in order to develop novel therapies to specifically kill cancer cells.

Research Description

Cell signaling is part of an intricate system of events activated by various stimuli that coordinate cell responses. Our laboratory is interested in unveiling pathways involved in cancer development in order to target them and control cancer progression. For over two decades, Dr. Platanias’ laboratory has identified several cellular cascades activated by IFN, ATRA and arsenic. Our research on Type I IFN found an essential role for SKAR protein in the regulation of mRNA translation of IFN-sensitive genes and induction of IFN-α biological responses. We also provided evidence for unique function of mTORC2 complex in inducing Type I IFN response. Our studies on arsenic signaling revealed a direct binding of this compound to a kinase called AMPK as a mechanism underlying its anti-leukemic activity. Other work included the activation of biological responses by BCR-ABL oncoprotein through the mTOR pathway. Dr. Platanias’ laboratory is also involved in testing new compounds in combination with approved therapies in order to identify synergy and improve the risk/benefit ratios of current therapeutic regimens for patients.

Publications

View lab publications via PubMed.

For more information, visit the faculty profile page of Leonidas Platanias, MD, PhD.

Contact Us

Contact Dr. Platanias at 312-908-5250 or the Platanias Lab at 312-503-4500.

Lab Staff

Elspeth Beauchamp, PhD
Research Assistant Professor
312-503-4500

Frank Eckerdt
Research Assistant Professor
312-503-0292

Diana Saleiro
Research Assistant Professor
312-503-4500

Mariafausta Fischietti
Research Assistant Professor
312-503-4283

Ricardo Perez
Postdoctoral Fellow
312-503-4275

Candice Mazewski
Postdoctoral Fellow
312-503-4275

Dominik Nahotko
Graduate Student
312-503-4275

Jamie Guillen
Graduate Student
312-503-4275

Sarah Fenton
PSTP MD Fellow
312-503-4275

Sara Small
PSTP MD Fellow
312-503-4275

Liliana Ilut
Research Technologist 2
312-503-4500

Aneta Baran
Lab Manager/Senior Researcher
312-503-4275

 Murali Prakriya Lab

Calcium signaling, inflammation, and brain function

Research Description

Research in the laboratory of Murali Prakriya, PhD, is focused on the molecular and cellular mechanisms of intracellular calcium (Ca2+) signaling. Ca2+  is one of the most ubiquitous intracellular signaling messengers, mediating many essential functions including gene expression, chemotaxis and neurotransmitter release. Cellular Ca2+ signals generally arise from the opening of Ca2+-permeable ion channels, a diverse family of membrane proteins. We are studying Ca2+ signals arising from the opening of store-operated Ca2+  channels (SOCs). SOCs are found in the plasma membranes of virtually all mammalian cells and are activated through a decrease in the calcium concentration ([Ca2+]) in the endoplasmic reticulum (ER), a vast membranous network within the cell that serves as a reservoir for stored calcium. SOC activity is stimulated by a variety of signals such as hormones, neurotransmitters and growth factors whose binding to receptors generates IP3 to cause ER Ca2+ store depletion.

The best-studied SOC is a sub-type known as the Ca2+ release activated Ca2+  (CRAC) channel encoded by the Orai1 protein. CRAC channels are widely expressed in immune cells and generate Ca2+  signals important for gene expression, proliferation and the secretion of inflammatory mediators. Loss of CRAC channel function due to mutations in CRAC channel genes leads to a devastating immunodeficiency syndrome in humans. Our goals are to understand the molecular mechanisms of CRAC channel activation, and their physiological roles especially in the microglia and astrocytes of the brain, and in the airway epithelial cells of the lung.

Recent Findings

Despite the fact that CRAC channels are found in practically all cells, their properties and functions outside the immune system remain largely unexplored. In order to fill this gap, we have begun investigation of CRAC channel properties and their functions in two major organ systems: in the brain and the lung.

  • In the brain, we are studying the role of CRAC channels for dendritic Ca2+ signaling in excitatory neurons of the hippocampus, and their role in synaptic plasticity and cognitive functions. We have found that CRAC channels formed by Orai1 are critical for amplifying glutamate receptor evoked calcium signals in dendritic spines of hippocampal neurons, and this step is essential for driving structural and functional measures of synaptic plasticity and cognitive processes involving learning and memory.
  • In a second project, we are studying the role of CRAC channels in driving neuroinflammation. We have found that CRAC channels formed by Orai1 are essential for the production and release of proinflammatory cytokines and chemokines in microglia and astrocytes.  We are examining the relevance of this pathway for mediating inflammatory and neuropathic pain.
  • A third project is examining the role of CRAC channels for mediating pro- and anti-inflammatory processes in the lung. We have found that CRAC channels are a major mechanism for mobilizing Ca2+ signals in lung epithelial cells, and the downstream production of both pro- and anti-inflammatory mediators. We are examining the relevance of this signaling for lung inflammation in the context of asthma.

For lab information and more, see Dr. Prakriya’s faculty profile and lab website.

Publications

See Dr. Prakriya's publications on PubMed.

Contact

Contact Dr. Prakriya at 312-503-7030.

Lab Staff

Research Faculty

Megumi Yamashita

Postdoctoral Fellows

Kirill Korshunov, Priscilla Yeung

Graduate Students

Kaitlyn Demeulenaere, Se’ FerrellTim Kountz, Michaela Novakovic

Technical Staff

Megan Martin, Martinna Raineri Tapies

 Arthur Prindle Lab

Synthetic biology in microbial communities

Research Description

The Prindle lab is interested in understanding how molecular and cellular interactions give rise to collective behaviors in microbial communities. While bacteria are single celled organisms, we now understand that most bacteria on our planet reside in the context of structured multicellular communities known as biofilms. However, most bacterial research is still performed on domesticated lab strains in well-mixed conditions. We simply do not know enough about the biology and behavior of the most pervasive life form on our planet. It is our goal to discover and understand these behaviors so that we may apply our understanding to engineer biomolecular systems as solutions to challenging biomedical problems, such as antibiotic resistance. To do this, we also work on developing technologies that can characterize collective metabolic and electrochemical dynamics that emerge in the context of biofilms.

For more information, see Dr. Prindle's lab website.

Publications

See Dr. Prindle’s publications on PubMed.

Contact

Contact Dr. Prindle

 Susan Quaggin Lab

Uncovering the molecular mechanisms of diabetic vascular complications, thrombotic microangiopathy, glomerular diseases and glaucoma

Our lab focuses on the basic biology of vascular tyrosine kinase signaling in development and diseases of the blood and lymphatic vasculature.  Our projects include uncovering the molecular mechanisms of diabetic vascular complications, thrombotic microangiopathy, glomerular diseases and glaucoma.  Utilizing a combination of mouse genetic, cell biologic and proteomic approaches, we have identified key roles for Angiopoietin-Tie2 and VEGF signaling in these diseases.  Members of the lab are developing novel therapeutic agents that target these pathways.  

For more information, please see the faculty profile of Susan Quaggin, MD

Publications

See Dr. Quaggin's publication in PubMed

Contact

Email Dr. Quaggin

 Gabriel Rocklin Lab

We develop high-throughput methods for protein biophysics and protein design, with a focus on protein therapeutics

Research Description

Key questions include: How do protein sequence and structure determine folding stability, conformational dynamics, and resistance to aggregation/degradation-inducing stresses? Can we quantitatively predict these protein "phenotypes" from genotype (sequence) using computational modeling? How do we design protein therapeutics that optimize these phenotypes for a particular application? To answer these questions, we combine large-scale de novo computational protein design with high-throughput methods such as display selections, mass spectrometry proteomics, and next-generation sequencing, enabling us to test thousands of proteins in parallel. By combining these technologies, we seek to develop efficient "design-test-analyze" cycles, iterating our way to an improved, quantitative understanding of protein biophysics and more advanced protein therapeutics.

For lab information and more, see Dr. Rocklin's faculty profile and lab website.

Publications

See Dr. Rocklin's publications on PubMed.

Contact

Contact Dr. Rocklin at 312-503-4892.

Lab Staff

Postdoctoral Fellows

Sugyan Dixit, Jane Thibeault, Kotaro Tsuboyama

Graduate Students

Tae-Eun Kim, Cydney Martell, Claire Phoumyvong, Tanu Priya

Research Fellows

Radhika Dalal, Andres Lira

Technical Staff

Robert Ludwig

Visiting Scholar

Allan Ferrari

 Robert P. Schleimer Lab

The Schleimer Lab investigates molecular and cellular mechanisms underlying pathogenesis of Chronic Rhinosinusitis and actions of anti-inflammatory steroids. We have a collaboration of bench scientists, Clinical Allergists and ENT surgeons.

Our group studies Chronic Rhinosinusitis, a disease of the nose and sinuses that affects over 30 million Americans.  Using tissue samples collected from patients undergoing surgery for Chronic Rhinosinusitis through our close collaboration with Clinical Allergists and ENT surgeons, we study the gene and protein expression profiles as well as resident immune cell populations that are altered in disease in order to identify and explore potential mechanisms of disease progression and identify targets for therapeutic development. This work has provided evidence of dysregulation of epithelial immune barrier function, innate immunity, fibrin deposition and adaptive immune responses as potential mechanisms of disease progression. In the realm of epithelial barrier, we are currently investigating the mechanism by which Oncostatin M drives epithelial barrier degeneration. Additional research in our lab is pursuing mechanisms of fibrin deposition and the contributions of alterations in the fibrin system to polyp formation. Other experiments are working to reveal the potential impact of abnormal B cell activation in polyps. Finally, we continue our long running exploration of the cellular and molecular mechanisms of anti-inflammatory actions of glucocorticoid steroids and the causes of apparent steroid resistance in selected individuals and diseases.

Publications

View Dr. Schleimer's publications at PubMed

For more information, visit the faculty profile of Robert Schleimer, PhD.

Contact

Contact Dr. Schleimer at 312-503-0076

Lab Staff

Roderick Carter
Senior Research Technician

Yan Feng
Visiting Scholar

Yoshimasa Imoto
Visiting Scholar

James Norton
Laboratory Manager

Kathryn Pothoven
Graduate Student

Lydia Suh
Senior Research Technician

Toru Takahashi
Visiting Scholar

 Evan Scott Lab

Engineering- and materials-based strategies to target inflammation

Research Description

My research objectives are to investigate the basic immunological processes contributing to diverse inflammation-driven pathologies and to develop targeted therapeutic approaches using engineering- and materials-based strategies. More specifically, I aim to achieve controlled elicitation or suppression of the immune system via the rational design of biomimetic delivery systems that target key inflammatory cell populations. These efforts are focused on addressing fundamental problems in the areas of heart disease, vaccination, transplant tolerance, glaucoma, and cancer immunosuppression.

For more information, see Dr. Scott's faculty profile.

Publications

See Dr. Scott's publications

Contact

Email Dr. Scott

Phone at  847 467 6719

 

 Eugene Silinsky Lab

Studying neuromuscular transmission and its modulation by adenosine derivatives under normal conditions and in disease

Research Description

Dr. Silinsky, assisted by his collaborator and laboratory co-director Dr. Timothy Searl, Research Assistant Professor, studies neuromuscular transmission and its modulation at both voluntary (skeletal) and involuntary (autonomic) neuromuscular junctions.

Nerve endings communicate with their receiving cells by the secretion of primary neurotransmitter substances and also regulate their own activity by the co-release of neuromodulatory substances. Adenosine derivatives are such modulatory substances. Indeed, we now know that most synapses in the vertebrate nervous system are responsive to physiological levels of extracellular adenosine derivatives.

The Silinsky laboratory studies the effects of adenosine and adenosine triphosphate (ATP) on the functions of the peripheral nervous system. These molecules were originally implicated as important components of metabolic pathways and in the subtle control of the rate of chemical reactions. However, adenosine and ATP have been found by the Silinsky laboratory and other laboratories to be essential modulators of neuronal function and also to be neurotransmitters in disease states.

For example, we have found that adenosine, derived from the ATP released from nerve endings after repetitive activation, is an important mediator of the fatigue of our voluntary muscles. In addition, ATP may be the cause of overactive bladder, as ATP is released from overactive bladder and then acts on ATP-gated ion channels to cause the bladder muscle over-activity. These ATP-gated channels are absent from normal bladder muscles but their presence in disease states overwhelms the normal communication between nerve and bladder muscle and appears to be a major cause of the debilitating symptoms suffered by overactive bladder patients. We are also studying the effects of botulinum toxins, which are used to treat overactive bladder, as therapeutic tools and as tools to study modulation of neurotransmitter secretion at nerve endings.

Important Findings

  • The first discovery that ATP is released together from motor nerve endings with the neurotransmitter acetylcholine and in quantal units (citations 1 and 2 below). This work led to our finding of specific adenosine receptors on nerve endings (the first evidence for adenosine receptors on any neuron-citation 3) and the finding that ATP, and after hydrolysis to adenosine, acts on specific adenosine receptors to mediate neuromuscular depression (citation 4).
  • Evidence that botulinum toxins can either increase or obtund modulation of calcium currents in nerve endings. Citation 5 was a featured PNAS article (with the supplementary material providing a detailed description of the different botulinum toxin fractions at motor nerve endings to skeletal muscle). This article also describes differences in the effects of botulinum toxins between wild type and mutant mice.
  • Evidence that the traditional textbook assumption that neuromuscular depression during low frequency clinical assessment conditions is due to depletion of neurotransmitter is wrong-this depression is due to a decrease in nerve terminal calcium currents (Citation 6).
  • Evidence that adenosine receptors on nerve ending can be constitutively active in the absence of adenosine (Citation 7).
  • Evidence that the nerve endings innervating the mammalian bladder are primed in a manner similar to other synapses in the peripheral and central nervous systems (citation 8).

Citations to the Important Findings:

1.  Silinsky EM (1975) On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals. J Physiol 247: 145 162.
2.  Silinsky EM & Redman RS (1996) Synchronous release of ATP and neurotransmitter within milliseconds of a motor nerve impulse in the frog. J Physiol 492.3: 815-822.
3.  Silinsky EM (1980) Evidence for specific adenosine receptors at cholinergic nerve endings. Brit J Pharmacol 71: 191-194,
4.  Redman RS & Silinsky EM (1994) ATP released together with acetylcholine as the mediator of neuromuscular depression at frog motor nerve endings. J Physiol 477.1:117-127.
5.  Silinsky EM (2008) Selective disruption of the mammalian secretory apparatus enhances or eliminates calcium current modulation in nerve endings. Proc Natl Acad Sci USA  105: 6427-32.
6.  Silinsky EM (2013) Low frequency neuromuscular depression is a consequence of a reduction in nerve terminal Ca2+ currents at mammalian motor nerve endings. Anesthesiology 119:326-334.
7.  Searl TJ & Silinsky EM (2012) Evidence for constitutively-active adenosine receptors at mammalian motor nerve endings. Eur J Pharmacol 685: 38-41.
8.  Searl TJ & Silinsky EM (2012) Modulation of purinergic neuromuscular transmission by phorbol dibutyrate is independent of protein kinase C in the murine urinary bladder. J Pharmacol Exp Ther 342:1-6.

Current and Planned Projects

  • Investigating the effects of adenosine antagonists as potential treatments for diseases associated with excessive neuromuscular fatigue (e.g. myasthenia gravis) and for botulinum toxin poisoning  
  • Investigating the effects of aging at the neuromuscular junction using animal models (in collaboration with Dr. Richard Lieber’s laboratory at Shirley Ryan AbilityLab)
  • Investigating the causes of overactive bladder in mouse models and in human biopsies (in collaboration with the Department of Urology at Northwestern University and Southern Illinois University) as well as the potential therapeutic advantages of different botulinum toxin serotypes in bladder disorders.

For lab information and more, see Dr. Silinsky's faculty profile.

Publications

See Dr. Silinsky's publications on PubMed.

Contact

Contact Dr. Silinsky at 312-503-8287.

 Alexander Stegh Lab

Dr. Stegh’s lab aims to define and target the oncogenome of glioblastoma.

Research Description

Our research program is aimed at understanding the genetic program that underlies the pathogenesis of Glioblastoma multiforme (GBM), the most prevalent and malignant form of brain cancer. Applying a combination of cell/molecular biology, oncogenomic and mouse engineering approaches, we are dedicated to systematically characterize novel gliomagenic oncogenes and tumor suppressors. We will functionally delineate and validate these pathways using cell culture and animal models and develop novel nanotechnological approaches to target these aberrations in established tumors.

For more information see the faculty profile of Alexander H. Stegh MD, PhD, or visit the Alexander H. Stegh Lab website.

Recent Publications

View Dr. Stegh's full list of publications at PubMed.

Contact

Email Alexander Stegh, MD, PhD 

Phone: 312-503-2879

Twitter: @ahstegh

 Geoffrey Swanson Lab

Studying glutamate receptors in the modulation of neurotransmission and induction of synaptic plasticity

Research Description

Geoffrey Swanson’s, PhD, laboratory studies the molecular and physiological properties of receptor proteins that underlie excitatory synaptic transmission in the mammalian brain. Current research focuses primarily on understanding the roles of kainate receptors, a family of glutamate receptors whose diverse physiological functions include modulation of neurotransmission and induction of synaptic plasticity. We are also interested in exploring how kainate receptors might contribute to pathological processes such as epilepsy and pain. The laboratory investigates kainate receptor function using a diverse group of techniques that include patch-clamp electrophysiology, selective pharmacological compounds, molecular and cellular techniques and gene-targeted mice.

Current Projects

  • Isolation and characterization of new marine-derived compounds that target glutamate receptors
  • Kainate receptors in hippocampal synaptic transmission
  • Mechanisms of kainate receptor assembly and trafficking

For lab information and more, see Dr. Swanson’s faculty profile and lab website.

Publications

See Dr. Swanson's publications on PubMed.

Contact

Contact Dr. Swanson at 312-503-1052.

Lab Staff

Postdoctoral Fellow

Sakiko Taniguchi, Rajesh Vinnakota

Graduate Students

Erica Binelli, Brynna Webb

Technical Staff

Srinivasan Pandiyan, Helene Lyons-Swanson

 Jacob I. Sznajder Lab

The Sznajder Lab investigates the mechanisms of acute lung injury as related to aging, high CO2, low oxygen, lung cancer and influenza infection.

Seasonal influenza infection affects a significant proportion of the population in the US and worldwide and while most patients infected with influenza A virus (IAV) recover without sequelae, in many patients influenza virus infection may cause ARDS. Alveolar epithelial cells (AEC) are targets for IAV and play an important role in mounting the initial host response. The Sznajder Lab hypothesizes that the alveolar epithelium plays an important effector role in protecting the lung from severe injury. Findings indicate that the degradation of PKCζ, which triggers the down-regulation of Na,K-ATPase, by the E3 ligase HOIL-1L decreases AEC death.  HOIL-1L is a member of the Linear Ubiquitination Assembly Complex (LUBAC) and the lab studies whether LUBAC participates in the modulation of the inflammatory intensity in the lung epithelium during IAV infection. Also, they are investigating the mechanisms by which modest inhibition of the Na,K-ATPase,  whether pharmacologic inhibition of the Na,K-ATPase by cardiotonic steroids such as ouabain are protective by inhibiting virus replication.

Studies suggest that signals from the injured lung during IAV infection disrupt skeletal muscle proteostasis and contribute to skeletal muscle dysfunction. The slower recovery of the skeletal muscle function in aged mice during IAV pneumonia is the consequence of diminished proteostatic reserve in cells responsible for regenerating the damaged skeletal muscle.

Hypercapnia (high pCO2) is observed in patients with lung diseases such as chronic obstructive pulmonary disease (COPD), broncho-pulmonary dysplasia and advanced neuromuscular diseases. The lab hypothesizes that hypercapnia promotes the ubiquitin-proteasome mediated muscle degradation and impairs the function of muscle satellite cells required for its regeneration.

Alveolar fluid reabsorption is effected by vectorial Na+ transport via apical Na+ channels and basolateral Na,K-ATPase of the alveolar epithelium. We and others have reported that β-adrenergic agonists upregulate the Na,K-ATPase in AEC  by increasing the traffic and recruitment of Na,K-ATPase containing vesicles into the cell membrane, resulting in increased catalytic activity. Moreover, GPCR-mediated upregulation of the Na,K-ATPase resulted in increased alveolar fluid clearance in normal lungs and in rodent models of lung injury.  We are investigating mechanisms of Na,K-ATPase regulation and active Na+ transport in lungs which will help with the design of new strategies to increase lung edema clearance.

Publications

View Dr. Sznajder's publications on PubMed

For more information visit the faculty profile of Jacob Sznajder, MD.

Contact

Contact Dr. Sznajder at 312-908-7737 or the Sznajder Lab at 312-503-1685.

Lab Staff

Laura Brion, PhD
Visiting Scholar
312-503-1685

Patricia Brazee
DGP Graduate Student
312-503-1685

Ermelinda Ceco, PhD
Postdoctoral Research Fellow
312-503-1685

Nina Censoplano, MD
Fellow, Pediatric Critical Care
312-503-1685

Laura A Dada, PhD
Research Associate Professor
312-503-5397

Jeremy Katzen, MD
Research Fellow
312-503-1685

Emilia Lecuona, PhD
Research Associate Professor
312-503-5397

Natalia Magnani, PhD
Postdoctoral Research Fellow
312-503-1685

Masahiko Shigemura, PhD
Postdoctoral Research Fellow
312-503-1685

Lynn C. Welch
Research Laboratory Manager
312-503-1685

Weronika Zuczek
Research Technologist I
312-503-1685

 C. Shad Thaxton Lab

Fabricating new nanomaterials and translational nanotechnology with regard to nanoparticle-based molecular diagnostics and nanotherapeutics.

Research Description

Shad Thaxton MD, PhD, invented, synthesized, and characterized the first biomimetic high-density lipoprotein nanoparticles. High density lipoproteins (HDLs) are natural nanoparticles that circulate in the human body to carry cholesterol. Cholesterol carried by HDLs is often referred to as “good cholesterol” because HDL blood levels inversely correlate with the development of cardiovascular disease. The Thaxton Group utilizes a gold nanoparticle scaffold to assemble the natural surface chemical components of HDLs to create synthetic HDL nanoparticles. The HDL nanoparticles recapitulate the size, shape, surface chemistry, and cholesterol binding properties of natural HDLs. As such, The Thaxton Lab is using these unique biomimetic materials to better understand the structure-function properties of natural HDLs and also as potential therapies for atherosclerosis and heart disease.

For more information, see the faculty profile of  C. Shad Thaxton, MD, PhD

Publications

View Dr. Thaxton's other publications at PubMed

Contact

Email Dr. Thaxton

Phone 312-503-1826

Lab Staff

Post-doctoral Fellows

Nick Angeloni, Kannan Mutharasan, Jonathan Rink

Graduate Students

Kaylin M. McMahon, Michael Plebanek, Sushant Tripathy, Andrea Luthi

Research Technician

Amritha Singh

 Edward Thorp Lab

The Thorp laboratory studies how immune cells coordinate tissue repair and regeneration under low oxygen, such as after a heart attack.

Research Interests

The Edward Thorp Lab studies the crosstalk between immune cells and the cardiovascular system and, in particular, within tissues characterized by low oxygen tension or associated with dyslipidemia, such as during myocardial infarction. In vivo, the lab interrogates the function of innate immune cell phagocytes, including macrophages, as they interact with other resident parenchymal cells during tissue repair and regeneration. Within the phagocyte, the influence of hypoxia and inflammation on intercellular and intracellular signaling networks and phagocyte function are studied in molecular detail. Taken together, our approach seeks to discover and link basic molecular and physiological networks that causally regulate disease progression and in turn are amenable to strategies for the amelioration of cardiovascular disease.

Publications

For additional information, visit the Thorp Lab site or view the faculty profile of Edward B Thorp, PhD.

View Dr. Thorp's publications at PubMed

Contact

Contact the Thorp lab at 312-503-3140.

Lab Staff

Shuang Zhang
PhD student
312-503-3140

Xin-Yi Yeap, MS
Lab Manager and Microsurgery
312-503-3140

 Lu Wang Lab

Investigating mutations in epigenetic factors that contribute to human cancer development

Research Description

Human Cancer Development: Understanding the Important Functions of Epigenetic Factor Mutations

Mutations and/or translocations within genes that encode for epigenetic factors, such as histone protein lysine methyltransferases (KMTs), lysine demethylases (KDMs), and DNA methyltransferases (DNMTs) are all common mechanisms involved in driving tumorigenesis (Cancer Cell. 2019, Feb 11; 35(2):168-176). We utilize state-of-the-art technologies that are designed to conduct epigenetic-related experiments, which allow us to directly uncover the underlying mechanisms of how mutations in epigenetic factors contribute to human cancer development (Nat Med. 2018, Jun; 24(6):758-769).

Novel Cancer Treatment Options: Targeting Dys-Regulated Epigenetic Factors

Misregulation of histone/DNA modifiers have emerged as a common therapeutic target option for treatments of different human diseases, including cancer. (Genes Dev. 2017, Oct 15; 31(20):2056-2066), Cancer Cell. 2014, Jan 13; 25(1):21-36, Sci Adv. 2015 Oct 9; 1(9):e1500463). Currently, several protein methyltransferases and demethylases have been identified, but their physiological significance has just begun to be elucidated. Our goal is to understand the relationship between dys-regulated epigenetic factors and cancer development through the use of these advanced technologies, such as CRISPR screening and experiments involving small inhibitor molecules. As a result, this could lead us to generate potential cancer treatment options by identifying the druggability of selected epigenetic factors, in order to develop a novel and more precise use of a drug that can be translational to clinical applications.

For lab information and more, see Dr. Wang’s faculty profile and lab website.

Publications

See Dr. Wang’s publications.

Contact

Contact Dr. Wang.

Lab Staff

Technical Staff

Aileen Szczepanski

 Martin Watterson Lab

Focusing on the role of protein phosphorylation pathways in disease onset and progression and their potential as drug discovery targets

Research Description

Current Projects

The role of calmodulin (CaM) mediated signal transduction pathways in physiology and pathophysiology

  • Using of emerging technologies to understand how CaM and a CaM-regulated enzyme could be encoded, expressed, regulated and assembled into a calcium signal transduction complex
  • Using of integrative (in vivo) chemical biology and molecular genetics to gain insight into how landmark CaM-regulated protein kinases are involved in physiology and pathophysiology

Integrative chemical biology and development of novel therapeutics for attenuation of disease progression

  • Using the “smart chemistry” approach integrated with “smart biology” screens for rapid discovery of novel small molecules with potential use in targeting pathophysiology progression related to diseases ranging from neurological disorders, cancer, inflammatory conditions, cardiovascular and pulmonary disease
  • Discovering and developing novel small molecule compounds that selectively attenuate the increased production of proteins called proinflammatory cytokines, which can cause tissue injury and disease when produced in excess

We ultimately hope to find, by targeting pathophysiology mechanisms which contribute to disease progression, a series of novel small molecules with potential to be effective against a variety of disorders.

For lab information and more, see Dr. Watterson’s faculty profile.

Contact

Contact Dr. Watterson at 312-503-0657.

Lab Staff

Adjunct Associate Professor

Jeff Pelletier

Research Associate Professor

Luda Shuvalov

Research Assistant Professor

Saktimayee Roy

Senior Research Associate

Tatiana Pundy

 Jindan Yu Lab

Understanding the genetic and epigenetic pathways to prostate cancer.

The Yu lab focuses on cancer genomics and translational cancer research.  At the current stage, our primary research interest is to understand aberrant transcriptional and epigenetic regulation of prostate cancer and to translate such knowledge into clinical applications.  We utilize high-throughput genomic techniques in combination with bioinformatics/statistical analysis to generate testable hypothesis.   We then test these hypotheses using traditional molecular and/or cellular biological approaches and examine the functional relevance of these innovative regulatory pathways in vitro and in vivo using cell lines and mouse models.  Based on the genetic and epigenetic underpinning of the disease, we pursue translational research to develop new biomarkers and novel therapeutics strategies for advanced prostate cancer.

Select Publications

Kim J, Lee Y, Lu X, Song B, Fong KW, Cao Q, Licht JD, Zhao JC, Yu J.  Polycomb- and Methylation-Independent Roles of EZH2 as a Transcription Activator.  Cell Reports. 2018 Dec 04. PMID: 30517868

Fong KW, Zhao JC, Song B, Zheng B, Yu J.  TRIM28 protects TRIM24 from SPOP-mediated degradation and promotes prostate cancer progression.  Nat Commun. 2018 Nov 27. PMID: 30479348

Fong KW, Zhao JC, Kim J, Li S, Yang YA, Song B, Rittie L, Hu M, Yang X, Perbal B, Yu JPolycomb-mediated disruption of an androgen receptor feedback loop drives castration-resistant prostate cancer.  CancerRes. 2016 Nov 4. PMID: 27815387

View all lab publications via PubMed.

For more information, visit the faculty profile page of Jindan Yu, MD/PhD or visit the Yu Laboratory website.

Contact Us

Contact Dr. Yu at 312-503-2980 or the Yu Lab at 312-503-3041.

Lab Staff

Will Ka-Wing Fong
Research Assistant Professor

Jonathan Zhao, MD, MS
Research Associate Professor

Nathan Damaschke, PhD
Postdoctoral Fellow

Yongik Lee, PhD
Postdoctoral Fellow

Xiaodong Lu, PhD
Postdoctoral Fellow

Gang Zhen, PhD
Postdoctoral Fellow

Xiaoyan Zhu, PhD
Postdoctoral Fellow

Galina Gritsina
Graduate Student

Kevin Park
Graduate Student

Rakshitha Jagadish
Masters Student

 Bin Zhang Lab

The Zhang Lab investigates the tumor-induced immune suppression.

Dr. Zhang’s laboratory work is focused on understanding the mechanisms of tumor-induced immune evasion. The overall goal is to develop novel and feasible strategies to improve cancer immunotherapy. He has been recently interested in the tumor microenvironment complexity whereby CD73 functions as an ecto-enzyme to produce extracellular adenosine, which limits anti-tumor T cell immunity. He is exploring the detailed mechanisms of CD73 by which the tumors evade the immune system using a combination of molecular, biochemical and mouse genetic approaches and to accomplish the targeted elimination of CD73 as a novel means to enhance cancer immunotherapy. Other ongoing studies involve: (1) Analyze the contribution of new key molecules including microRNAs from the perspective of cancer immunology in regulating regulatory T cells and/or myeloid derived suppressive cells;  (2) Define a novel use of pre-existing chemotherapy drugs to overcome tumor-mediated immunosuppression; (3) Characterize the role of novel molecules in tumor T cell immunity and autoimmunity; (4) Understand the differential immune regulation in GVHD vs. GVL; and (5) Develop new animal models that can be employed in preclinical studies to most reflect human clinical trials.

Publications

View lab publications via PubMed.

For more information, visit the faculty profile page of Bin Zhang, MD/PhD.

Contact Us

Contact Dr. Zhang at 312-695-6180 or the Zhang Lab at 312-503-2435.

Lab Staff

Siqi Chen
Graduate Student
312-503-2435

Donye Senon Dominguez
Graduate Student
312-503-2432

Jie Fan
Senior Technician
312-503-2435 

Alan Long
Grad student
312-503-2432

Lei Qin
Postdoc Scholar
312-503-2432

 Youyang Zhao Lab

The Zhao Lab studies the molecular mechanisms of endothelial regeneration and resolution of inflammatory injury as well as endothelial and smooth muscle cell interaction in the pathogenesis of pulmonary vascular diseases.

Research Description

Recovery of endothelial barrier integrity after vascular injury is vital for endothelial homeostasis and resolution of inflammation. Endothelial dysfunction plays a critical role in the initiation and progression of vascular diseases such as acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and atherosclerosis. A part of the research in the lab, employing genetically modified mouse models of human diseases, endothelial progenitor cells/stem cells, and translational research approach as well as nanomedicine, is to elucidate the molecular mechanisms of endothelial regeneration and resolution of inflammatory injury and determine how aging and epigenetics regulate these processes (J. Clin. Invest. 2006, 116: 2333; J. Exp. Med. 2010, 207:1675; Circulation 2016, 133: 2447).  We are also studying the role of endothelial cells in regulating macrophage functional polarization and resolving inflammatory lung injury. These studies will identify druggable targets leading to novel therapeutic strategies to activate the intrinsic endothelial regeneration program to restore endothelial barrier integrity and reverse edema formation for the prevention and treatment of ARDS in patients.

Pulmonary hypertension is a progressive disease with poor prognosis and high mortality. We are currently investigating the molecular basis underlying the pathogenesis.  We have recently identified the first mouse model of pulmonary arterial hypertension (PAH) with obliterative vascular remodeling including vascular occlusion and formation of plexiform-like lesions resembling the pathology of clinical PAH (Circulation 2016, 133: 2447). Our previous studies also show the critical role of oxidative/nitrative stress in the pathogenesis of PAH as seen in patients (PNAS 2002, 99:11375; J. Clin. Invest. 2009, 119: 2009). With these unique models and lung tissue and cells from idiopathic PAH patients, we will define the molecular and cellular mechanisms underlying severe vascular remodeling and provide novel therapeutic approaches for this devastating disease. 

The Zhao lab employs the state-of-the art technologies including genetic lineage tracing, genetic depletion, genetic reporter, and CRISPR-mediated in vivo genomic editing as well as patient samples to study the molecular mechanisms of acute lung injury/ARDS, and pulmonary hypertension and identify novel therapeutics for these devastating diseases. Current studies include 1) molecular mechanisms of endothelial regeneration and vascular repair following inflammatory lung injury induced by sepsis and pneumonia; 2) how aging and epigenetics regulate this process; 3) how endothelial cells regulate macrophage and neuptrophil function for resolution of inflammation and host defense; 4) stem/progenitor cells in acute lung injury and pulmonary hypertension and cell-based therapy; 5) mechanisms of obliterative pulmonary vascular remodeling; 6) molecular basis of right heart failure; 7) pathogenic role of oxidative/nitrative stress; 8) lung regeneration; 9) drug discovery; 10) nanomedicine.


Publications

View publications by Youyang Zhao in PubMed.

For more information, visit Dr. Zhao's Faculty Profile page

Contact

Email Dr. Zhao

Contact Dr. Zhao’s Lab at 773-755-6355

Lab Staff

Zhiyu Dai, PhD.
Research Assistant Professor

Xianming Zhang, PhD.
Research Assistant Professor

Narsa Machireddy, PhD.
Research Assistant Professor

Junjie Xing, PhD.
Research Scientist

Colin Evans, PhD.
Research Scientist

Varsha Suresh Kumar, PhD.
Research Scientist

Xiaojia Huang, PhD
Research Scientist

Hua Jin, PhD
Postdoctoral fellow

Yi Peng, PhD
Research Scientist

Mengqi Zhu, M.S.,
Graduate Student

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