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Stem Cell Biology and Regenerative Medicine

Research into the biology of stem cells with a particular focus on their use in regenerative medicine applications.

Labs in This Area

 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

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

 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

 Gemma Carvill Lab

Genetic causes and pathogenic mechanism that underlie epilepsy

Research Description

The primary goal of our research is to use gene discovery and molecular biology approaches to identify new treatments for epilepsy. We aim to 1) identify the genetic causes of epilepsy, 2) use stem cell models to understand how genetic mutations can cause epilepsy, 3) develop and test new therapeutics for this condition. Our work is based on the promise of precision medicine where knowledge of an individual’s genetic makeup shapes a personalized approach to care and management of epilepsy.

Current Projects

  • Next generation sequencing in patients with epilepsy
  • Alternative exon usage during neuronal development
  • Identify the regulatory elements that control expression of known epilepsy genes
  • Stem cell genetic models for studying the epigenetic basis of epilepsy

For more information, see Dr. Carvill's faculty profile or the Carvill Lab Website.

Publications

Please see Dr. Caraveo Piso's publications on PubMed.

Contact Information

Gemma L. Carvill, PhD

 Shi-Yuan Cheng Lab

Cancer stem cell biology, cellular signaling and therapy responses in human brain tumors, in particular, glioblastoma (GBM)

Research Description

      Integrated genomic analysis by TCGA revealed tat GBMs can be classified into four clinically relevant subtypes, proneural (PN), neural, mesenchymal (Mes) and classical GBMs with each characterized by distinct gene expression signatures and genetic alterations. We reported that PN and Mes glioma stem cells (GSCs) subtypes also have distinct dysregulated signaling pathways. Our current research focuses on novel mechanisms/cellular signaling of GSC biology, tumorigenesis, progression, invasion/metastasis, angiogenesis and therapy responses of GSCs and GBMs.

1. MicroRNAs (miRs) and non-coding RNAs in GSCs and GBMs – miRs and other small non-coding RNAs act as transcription repressors or inducers of gene expression or functional modulators in all multicellular organisms.  Dysregulated miRs/noncoding RNAs plays critical roles in cancer initiation, progression and responses to therapy. We study the mechanisms by which deregulated expression of miRs influence GBM malignant phenotypes through interaction with signaling pathways, that in turn, influence proneural (PN)- and mesenchymal (Mes)-associated gene expression in GSCs and GBM phenotypes. We study the molecular consequences and explore clinical applications of modulating miRs and signaling pathways in GBMs.  We are establishing profiles of non-coding RNAs in these GSCs and study mechanisms and biological influences of these non-coding RNAs in regulating GSC biology and GBM phenotypes. In addition, we explore novel therapeutic approaches of delivery of tumor suppressive miRs into GSC brain xenografts in animals.

2.  Autophagy in GBMs. (Macro)autophagy is an evolutionally conserved dynamic process whereby cells catabolize damaged proteins and organelles in a lysosome-dependent manner. Autophagy principally serves as an adaptive role to protect cells and tissues, including those associated with cancer. Autophagy in response to multiple stresses including therapeutic treatments such as radiation and chemotherapies provides a mechanism for tumor cell to survive and acquire resistance to therapies. Tumors can use autophagy to support and sustain their proliferation, survival, metabolism, invasiveness, metastasis and resistance to therapy. We study mechanisms by which phosphorylation, acetylation and ubiquitination of autophagy proteins regulate GSC and GBM phenotypes and autophagic response, which, in turn contributes to tumor cell survival, growth and resistance to therapy. We investigate whether disruption of these post-translational processes on autophagy proteins inhibits autophagy and enhances the efficacy of combination therapies for GBMs. We examine whether cross-talks between miRs, autophagy and oncogenic signaling pathways regulate GSC stemness and phenotypes.

3. Heterogeneity, epigenetic regulation, DNA damage and metabolic pathways in GSCs and GBMs. Intratumoral heterogeneity is a characteristic of GBMs and most of cancers. Phenotypic and functional heterogeneity arise among GBM cells within the same tumor as a consequence of genetic change, environmental differences and reversible changes in cell properties. Subtype mosaicism within the same tumor and spontaneous conversion of human PN to Mes tumors have been observed in clinical GBMs. We explore an emerging epigenetic marker with distinct functions such as DNA methylation together with genetic mapping of these markers to assess their contributions to GBM heterogeneity. In addition, compared with PN GSCs, DNA damage and glycolytic pathways are aberrant active in Mes GSCs. We investigate the mechanisms by which these pathways regulate GSC and GBM phenotypes and responses to therapies.

4. Oncogenic receptor tyrosine kinase (RTKs) signaling, small Rho GTPase regulators in GBM and GSCs: Small Rho GTPases such as Rac1 and Cdc42 modulate cancer cell migration, invasion, growth and survival. Recently, we described mechanisms by which EGFR and its mutant EGFRvIII and PDGFR alpha promote glioma growth and invasion by distinct mechanisms involving phosphorylation of Dock180, a Rac-specific guanidine nucleotide exchange factor (GEF) and DCBLD2, an orphan membrane receptor. We are currently investigating involvement of other modulators/GEFs and other Rho GTPases in modulating GSC and GBM phenotypes and responses to therapy.

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

Publications

View Dr. Cheng's complete list of publications in PubMed.

Contact Us

Shi-Yuan Cheng, PhD at 312-503-5314

Visit us on campus in the Lurie Building, Room 6-119, 303 E Superior Street, Chicago, Illinois 60611.

 

 John Kessler Lab

Focusing on the biology of neural stem cells and growth factors and their potential for regenerating the damaged or diseased nervous system.

Research Description

The Kessler laboratory focuses on the biology of neural stem cells and growth factors and their potential for regenerating the damaged or diseased nervous system. A major interest of the laboratory has been the role of bone morphogenetic protein (BMP) signaling in both neurogenesis and gliogenesis and in regulating cell numbers in the developing nervous system.  Both multipotent neural stem cells and pluripotent embryonic stem cells are studied in the laboratory. Recent efforts have emphasized studies of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hIPSC). The Kessler lab oversees the Northwestern University ESC and IPSC core and multiple collaborators use the facility. In addition to the studies of the basic biology of stem cells, the laboratory seeks to develop techniques for promoting neural repair in animal models of spinal cord injury and stroke. In particular, the lab is examining how stem cells and self-assembling peptide amphiphiles can be used together to accomplish neural repair. The lab is also using hIPSCs to model Alzheimer’s disease and other disorders. 

For more information see the faculty profile of John A Kessler, MD.

Publications

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

Contact

John Kessler, MD

 Evangelos Kiskinis Lab

Our laboratory investigates the molecular mechanisms that give rise to neurological diseases using human stem cell-derived neuronal subtypes.

Research Description

The broad objective of our laboratory is to understand the nature of the degenerative processes that drive neurological disease in human patients. We are primarily interested in Amyotrophic Lateral Sclerosis (ALS), Epileptic Syndromes as well as the age-associated changes that take place in the Central Nervous System (CNS). We pursue this objective by creating in vitro models of disease. We utilize patient-specific induced pluripotent stem cells and direct reprogramming methods to generate different neuronal subtypes of the human CNS. We then study these cells by a combination of genomic approaches and functional physiological assays. Our hope is that these disease model systems will help us identify points of effective and targeted therapeutic intervention.

Publications

View Dr. Kiskinis' publications at PubMed

For more information view the faculty profile of Evangelos Kiskinis, PhD, or the Evangelos Kiskinis Lab site.

Contact Information

Evangelos Kiskinis, PhD
Assistant Professor of Neurology

 Dimitri Krainc Lab

Understanding 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

 Tsutomu Kume Lab

The Kume Lab’s research interests focus on cardiovascular development, cardiovascular stem/progenitor cells and angiogenesis.

Research Description

Cardiovascular development is at the center of all the work that goes on in the Kume lab. The cardiovascular system is the first functional unit to form during embryonic development and is essential for the growth and nurturing of other developing organs. Failure to form the cardiovascular system often leads to embryonic lethality and inherited disorders of the cardiovascular system are quite common in humans. The causes and underlying developmental mechanisms of these disorders, however, are poorly understood. A particular emphasis in our laboratory has recently been the study of cardiovascular signaling pathways and transcriptional regulation in physiological and pathological settings using mice as animal models, as well as embryonic stem (ES) cells as an in vitro differentiation system. The ultimate goal of our research is to provide new insights into the mechanisms that lead to the development of therapeutic strategies designed to treat clinically relevant conditions of pathological neovascularization.

Publications

View Dr. Kume's publications on PubMed.

For more information, visit the faculty profile for Tsutomu Kume, PhD.

Contact Us

Contact Dr. Kume at 312-503-0623 or the Kume Lab at 312-503-3008.

Staff Listing

Austin Culver
MD Candidate
312-503-3008

Anees Fatima
Research Assistant Professor
312-503-0554

Christine Elizabeth Kamide
Senior Research Technologist
312-503-1446

Erin Lambers
PhD Candidate
312-503-5652

Ting Liu
Senior Research Technologist
312-503-3008

Jonathon Misch
Research Technologist
312-503-6153

 Yan Liu Lab

Hematopoietic stem cell self-renewal and pathogenesis of myeloid malignancies

Research Description

The Liu laboratory is interested in investigating the molecular mechanisms governing normal and malignant hematopoiesis, with an emphasis on understanding hematopoietic stem cell (HSC) self-renewal and pathogenesis of myeloid malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our long-term goals are to identify novel regulators of HSC self-renewal, understand the molecular mechanisms regulating their function, and develop novel therapeutic strategies to eliminate leukemia stem cells (LSCs) and improve leukemia treatment. We utilize molecular, genetic, immunological, biochemical, and pharmacological approaches as well as unbiased genome wide studies, including RNA-seq, ChIP-seq, ATAC-seq, and cytokine arrays, to investigate the molecular basis of HSC self-renewal and leukemogenesis. Major areas of focus include: 1) The role of tumor suppressor p53 in CHIP progression and pathogenesis of MDS; 2) Phosphatase PRL2 in HSC self-renewal and leukemogenesis; 3) Polycomb Repressive Complex 1 (PRC1) in HSC self-renewal and terminal differentiation.

For more information, visit Dr. Liu's faculty profile page.

Publications

View Dr. Liu's publications at PubMed.

Contact

Email Dr. Liu

 

 

 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

 Hans-Georg Simon Lab

Development and regenerative repair of vertebrate limbs and hearts

Research Description

The development of organs during embryogenesis and their repair during adulthood are biological problems of very practical importance for regenerative medicine.

Using both newt and zebrafish model organisms that naturally rebuild lost structures as adults, we identified evolutionarily conserved gene activities indicative of a molecular signature of regeneration. Particularly, we found the dynamic remodeling of the extracellular matrix (ECM) to be key in instructing cell behaviors that are critical for initiating and maintaining regenerative processes. These findings point to new opportunities for the enhancement of regenerative wound healing in mammals through the manipulation of the local extracellular environment.

As a new research direction, we are studying an unexpected hyperactive blood clotting phenotype in mice deficient for the actin-associated protein Pdlim7. The Pdlim7 knockout mouse provides strong translational opportunities as a novel model to better understand the causes and possible treatments of hypercoagulopathies.

For more information visit the faculty profile of Hans-Georg Simon, PhD.

Publications

View all publications on PubMed

Contact

Email Dr. Simon

Phone Dr. Simon at 773-755-6391 or the Simon Lab at 773-755-6372.

 Greg Smith Lab

Cell and molecular biology of herpesvirus invasion of the nervous system

Research Description

We investigate the relationship between infection of the nervous system by herpesviruses and disease outcome. Some of the most traumatic diseases – including polio, rabies and encephalitis – result from infections of the nervous system.  In contrast, herpesviruses are highly proficient at infecting the nervous system, yet normally do not cause neurological disease.  This is achieved in part by self-imposed restrictions encoded within the viruses that limit viral reproduction and prevent dissemination into the brain.  For the individual, this results in a relatively benign infection, yet the virus becomes a life-long occupant of the nervous system that will periodically reemerge at body surfaces to infect others. Unfortunately, this infectious cycle can go awry resulting in several forms of severe disease (i.e. keratitis and encephalitis).

We have pioneered methods to genetically manipulate herpesviruses and visualize individual viruses in living neurons. Using these methods, we are studying the mechanisms by which the virus achieves its stringently controlled infectious cycle. Current genetic manipulations are based on a full-length infectious clone of the herpesvirus genome. The clone was made as a bacterial artificial chromosome (BAC) in E. coli. Transfection of purified E. coli BAC plasmid into permissive eukaryotic cells is sufficient to initiate viral infection, allowing for immediate examination of viral mutant phenotypes in a variety of biological assays.  For example, by fusing the green fluorescent protein (GFP) to a structural component of the viral capsid, individual viral particles can be tracked within the axons of living neurons during both entry and egress phases of the infectious cycle. Studies in culture can be complemented by examining the pathogenesis of mutant viruses in rodent models of infection.

Using these methods, we have discovered key aspects of cellular infection, viral assembly and intracellular transport. Looking forward, we are continuing to pursue our multidisciplinary approach of combining neuroscience, cell biology, bacterial genetics and virology to better understand these important pathogens.

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

Publications

See Dr. Smith's publications on PubMed.

Contact

Contact Dr. Smith at 312-503-3745 or the lab at 312-503-3744.

Lab Staff

Research Faculty

Sarah Antinone 

Postdoctoral Fellows

Oana Maier

Graduate Students

Kennen Hutchison, DongHo Kim, Caitlin Pegg, Jen Ai Quan

Technical Staff

Austin Stults 

 Beatriz Sosa-Pineda Lab

The Sosa-Pineda lab studies studies the regulation of acinar cell development and plasticity in the pancreas, hepatic cell fate, and liver zonation. We also investigate mechanisms that promote pancreas metastasis.

Research Description

Using genetically modified mouse models and cutting-edge technologies, we investigate how the complex architecture of the mammalian pancreas and liver is established during development. We also investigate how acute or chronic injury affect liver zonation and exocrine pancreas homeostasis, and the role of chromosomal instability in pancreatic tumor formation and metastasis.

 

For more information, visit the faculty profile of Beatriz Sosa-Pineda, PhD or the Sosa-Pineda lab web site.

Publications

View Dr. Sosa-Pineda's publications at PubMed

Contact

Email Dr. Sosa-Pineda

Phone 312-503-2296

 Rui Yi Lab

Investigate mechanisms of skin development, stem cells, aging and cancer at the single-cell level

Research Description

Mammalian skin and its appendages function as the outermost barrier of the body to protect inner organs from environmental hazards and keep essential fluid within. Our research program studies mechanisms that govern cell fate specification, stem cell maintenance and aging as well as initiation and progression of cancer. We use single-cell genomics and computational tools, live animal imaging and genetically engineered mouse models to study gene expression regulation mediated by transcription factors, epigenetic regulators and post-transcriptional mechanisms mediated by miRNAs and RNA binding proteins at the single-cell resolution in mammalian skin. 

Our research aims to address several fundamental questions in stem cell biology: how the developmental potential of embryonic progenitors and adult tissue stem cells is transmitted or restricted in their progenies at the molecular level when they go through critical transitions such as cell fate specification, self-renewal of stem cells as well as stress response, and how these regulatory mechanisms go awry in aging and diseases. Answers to these questions will help to manipulate skin stem cells for regenerative medicine and discover new treatment for human skin diseases.​

View all lab publications via PubMed.

For more information, visit the faculty profile page of Rui Yi, PhD or visit the Yi Laboratory website.

Contact Us

Email Dr. Yi

 

 

 

 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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