Research into normal development, developmental diseases and the function and potential uses of stem cells.
All Labs In This Area
Mechanisms of prostate cancer initiation, progression and recurrence and strategies to therapeutically target these processes
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.
See Dr. Abdulkadir's publications in PubMed.
Meejeon Roh—Research Assistant Professor
Yvonne Feeney—Lab Manager
Tanushri Sengupta—Research Associate
Kenji Unno—Research Associate
Rose Njoroge—Graduate Student
Rajita Vatapalli—Graduate Student
Lab Telephone: 312-503-5031
Investigating dopamine neurogenesis and subtypes; studying the role of microRNAs in Schwann cell (SC) differentiation.
Topic 1. Mechanisms underlying dopamine neurogenesis
The floor plate, the ventral organizing center in the embryonic neural tube, patterns the neural tube by secreting the potent morphogen Shh. Using genetic fate mapping, we have recently shown that the midbrain floor plate, unlike the hindbrain and spinal cord floor plate, is neurogenic and is the source of midbrain dopamine neurons (Joksimovic, et al, 2009 Nature Neuroscience, Joksimovic et al. 2009 PNAS). We are interested in understanding pathways that are involved in floor plate neurogenesis and production of dopamine neurons. We have shown that Wnt signaling is critical for the establishment of the dopamine progenitor pool and that miRNAs may modulate the dosage and timing of the Wnt pathway (Anderegg et al, PloS Genetics 2013).
Topic 2. Deconstructing Dopaminergic Diversity
The neurotransmitter dopamine, produced mainly by midbrain dopaminergic neurons, influences a spectrum of behaviors including motor, learning, reward, motivation and cognition. In accordance with its diverse functions, dopaminergic dysfunction is implicated in a range of disorders affecting millions of people, including Parkinson’s disease (PD), schizophrenia, addiction and depression. How a small group of neurons underpins a gamut of key behaviors and diseases remains enigmatic. We postulated that there must exist several molecularly distinct dopaminergic neuron populations that, in part, can account for the plethora of dopaminergic functions and disorders. We are currently working to test this hypothesis and define dopamine neuron subtypes.
Topic 3. MicroRNAs in Schwann cell (SC) differentiation
MicroRNAs, by modulating gene expression, have been implicated as regulators of various cellular and physiological processes including differentiation, proliferation and cancer. We have studied the role of microRNAs in Schwann cell (SC) differentiation by conditional removal of the microRNA processing enzyme, Dicer1 (Yun et al, 2010, J Neurosci) . We reveal that mice lacking Dicer1 in SC (Dicer1 cKO) display a severe neurological phenotype resembling congenital hypomyelination. SC lacking Dicer1 are stalled in differentiation at the promyelinating state and fail to myelinate axons. We are beginning to determine the molecular basis of this phenotype. Understanding this will be important not only for congenital hypomyelination, but also for peripheral nerve regeneration and SC cancers.
For more information, please see Dr. Awatramani's faculty profile.
View Dr. Awatramani's complete list of publications in PubMed.
Rajeshwar Awatramani, PhD at 312-503-0690
Research Assistant Professor
Milan Joksimovic, Assistant Professor, Medical College of Wisconsin
Angela Anderegg, postdoctoral fellow
Natalya Cherepanova, MSTP student, U. Iowa
Meera Patel, graduate student, U. of Chicago
Studying the role of the glucocorticoid receptor in carcinogenesis and stem cell maintenance. Involved in development GR-targeted therapies in skin.
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.
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
Investigating the application of human induced pluripotent stem cells to study the pharmacogenomics of chemotherapy off-target toxicity and efficacy
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.
- Human induced pluripotent stem cells predict breast cancer patients’ predilection to doxorubicin-induced cardiotoxicity
- Chemically defined generation of human cardiomyocytes
- 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
See Dr. Burridge's publications on PubMed.
Contact Dr. Burridge at 312-503-4895.
Clinical Research Coordinator
Genetic causes and pathogenic mechanism that underlie epilepsy
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.
- 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
Please see Dr. Caraveo Piso's publications on PubMed.
Cancer stem cell biology, cellular signaling and therapy responses in human brain tumors, in particular, glioblastoma (GBM)
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.
View Dr. Cheng's complete list of publications in PubMed.
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.
Research Associate Professor
Namratha Sastry (rotating)
The Crispino laboratory studies the mechanisms of normal and malignant blood cell growth.
Research in the Crispino laboratory is focused on investigating the regulatory mechanisms governing normal and malignant blood cell development, with an emphasis on understanding the growth of erythroid cells (red blood cells) and megakaryocytes (platelet-producing cells). Major areas of focus include: 1) Understanding the link between Down syndrome and leukemia. We are investigating how mutations in GATA1, a key transcription factor that regulates megakaryocyte growth contribute to leukemia. We are also studying the mechanisms by which trisomy 21 promotes the development of leukemia with a long-term goal of unraveling the mystery of why children with DS are predisposed to leukemia. Our current efforts are focused on characterizing the contributions of two chromosome 21 genes: DYRK1A, a kinase and ERG, a transcription factor. 2) Development of novel therapeutics for human megakaryocytic malignancies. In collaboration with the Broad Institute, we identified several small molecules that induce proliferation arrest, polyploidization and maturation of malignant megakaryocytes. By a three-pronged target identification approach, we discovered that a key target of these small molecules is Aurora A Kinase. We are currently investigating the utility of AURKA inhibitors as potential new, targeted therapies for acute megakaryocytic leukemia. In addition, we have completed extensive pre-clinical studies to support the testing of AURKA inhibitors in a related blood disease named primary myelofibrosis, a subtype of the MPNs. 3) Investigating the mechanisms of red blood cell development. We are currently studying two aspects of red blood cell development. First, based on our previous discovery that the coalescence of cytoplasmic vesicles is required for enucleation of erythroblasts, we are probing the requirements for specific motor proteins in enucleation and identifying small molecules that enhance enucleation in culture. This research will aid in the development of new strategies to generate red blood cells for transfusion in vitro from stem cells. Second, in line with our expertise and significant interest in GATA1 biology, we are studying the effects of GATA1 mutations on erythropoiesis. We are using state of the art approaches to identify essential, direct GATA1 target genes whose expression depends on the presence of the full-length wild-type protein. This research is relevant to rare red blood cell disorders such as Diamond Blackfan Anemia. Overall, the lab seeks to make seminal basic science discoveries while simultaneously translating these discoveries in ways that will benefit patients with hematologic malignancies.
View lab publications via PubMed.
For more information, visit the faculty profile page of John Crispino, PhD.
Contact Dr. Crispino at 312-503-1504 or the Crispino Lab at 312-503-1433.
Gina Kirsammer, PhD
Research Assistant Professor
Paul Lee, MD, PhD
Pediatric Hematology/Oncology Fellow
Monika Stankiewicz, PhD
Praveen Suraneni, PhD
Benjamin Thompson, MD/PhD
Qiang (Jeremy) Wen, MD/PhD
Research Assistant Professor
Qiong Yang, MD/PhD
Mammalian ovarian and gamete biology and reproductive aging
Aging is associated with cellular and tissue deterioration and is a prime risk factor for chronic
diseases and declining health. The female reproductive system is the first to age in humans, with
a decline in egg quantity and quality beginning at ~35 years of age and menopause ensuing at
~50 years of age. Female reproductive aging has significant health consequences as it results in
endocrine function loss and is a leading cause of infertility, miscarriages, and birth defects.
Although aging hallmarks and mechanisms have been enumerated across multiple organ
systems and species, they have not been investigated in the context of mammalian reproductive
My research program integrates and builds upon my 18-year history in the field of reproductive
science and medicine to investigate the overarching hypothesis that deterioration of oocyteintrinsic
cellular pathways together with alterations in the ovarian environment underlie the ageassociated
decline in female gamete quantity and quality. Our work is at the interface of
reproductive aging and systemic aging; physiologic and iatrogenic reproductive aging; gamete,
follicle, and ovarian biology; and reproductive science and medicine. Our comprehensive insights
will help us design targeted interventions to potentially slow or counteract reproductive aging,
laying the foundation to simultaneously improve women’s fertile-span and health-span across
generations. In addition, reproductive aging mechanisms may inform those that precipitate
general aging, which occur up to decades later in life. Moreover, the mechanisms involved in
reproductive aging that we are investigating - aneuploidy, protein metabolism dysregulation,
and fibrosis and inflammation – are also central to other conditions such as cancer
pathogenesis. Thus, our research has broad impact and collaborative opportunities across
disciplines, which already include biochemistry, biophysics, toxicology and pharmacology, and
reproductive endocrinology and infertility.
Ultimately our work in reproductive aging will have direct impacts on public health in two ways.
First, reproductive aging affects all women, and menopause and premature aging of the ovary
accelerates aging in general. Such health consequences occur because ovarian hormones such
as estrogen, for example, are critical for cardiovascular, bone, immune, and cognitive functions.
Second, reproductive aging is associated with age-associated infertility, which has significant
societal, clinical, and health ramifications as more women globally are delaying childbearing.
For lab information and more, see Dr. Duncan's faculty profile.
Visit the Duncan Lab website
See Dr. Duncan's publications on PubMed.
Email Dr. Duncan
Development, function, dysfunction and degeneration of sensory receptor cells and neurons
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.
See Dr. García-Añoveros' publications on PubMed.
Research Assistant Professor
Lab Phone: 312-503-4246
Office Phone: 312-503-4245
Identifying and investigating novel molecular bases of cellular recognition that govern neuronal circuit assembly during human development and disease.
Developing neurons integrate into functional circuits through a series of cell recognition events, which include neuronal sorting, axon and dendrite patterning, synaptic selection, among others. Our research focuses on cell-surface recognition molecules that mediate interactions between neurons to discriminate and select appropriate targets in the developing brain. Additionally, we seek to uncover novel mechanisms of neural recognition that lead to brain connectivity defects in humans. To explore the broader roles for cell recognition molecules and their pivotal function in neural circuit development, our lab takes advantage of a battery of modern laboratory techniques. These approaches include animal and stem cell disease modeling, as well as next-generation sequencing and CRISPR/Cas9 gene editing. Identifying fundamental principles of cellular recognition in wiring circuits contributes to our understanding of neurological disorders and how neuronal dysfunction arises from aberrations during development of the human brain.
See Dr. Guemez-Gamboa's publications on PubMed.
Contact Dr. Guemez-Gamboa at 312-503-0752.
Role of MDia1 in the pathogenesis of del(5q) myelodysplasic syndromes
Our lab is interested in how cytoskeletal signaling, motor proteins and adhesion systems are integrated with chemical signaling pathways to regulate cell behavior and tissue differentiation and disease. The Ji lab studies small G proteins and downstream actin regulatory effectors that participate in enucleation during red cell development.
At the level of the nucleus, the Ji laboratory studies genes involved in erythroid lineage commitment, chromatin condensation and enucleation towards understanding how congenital red cell disorders and leukemia develop.
For more information, visit the faculty profile of Peng Ji, MD, PhD.
See Dr. Ji's publications in PubMed.
T helper cell differentiation and trafficking.
For lab information and more, see Dr. Kansas's faculty profile.
See Dr. Kansas's publications on PubMed.
Contact Dr. Kansas at 312-908-3237 or the lab at 312-908-3752.
Focusing on the biology of neural stem cells and growth factors and their potential for regenerating the damaged or diseased nervous system.
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.
View Dr. Kessler's full list of publications in PubMed.
Roles of chondroitin sulfates and genes/proteins in the chondroitin sulfate biosynthesis pathway in development and disease
My laboratory is interested in the functional roles of chondroitin sulfates and chondroitin sulfotransferase genes in mammalian development, disease and cellular signaling pathways. Specifically, we have been investigating the roles of the sulfotransferase C4ST-1/CHST11 and its chondroitin sulfate product CS-E in the contexts of breast cancer progression, the pediatric disease Costello syndrome, cardiovascular disease, developmental processes including embryonic stem cell differentiation and cell lineage determination and in the control of Wnt/beta-catenin and HRAS signaling. Our long-term goal is the development of carbohydrate-based pharmacological interventions for the treatment of human diseases, including cancer and cardiovascular disease.
For more information, view the faculty profile of Michael Klüppel, PhD.
See Dr. Klüppel's publications in PubMed.
Michael Klüppel, Ph.D.
Catherine M. Willis, Ph.D.
Robert Prinz, M.D.
Looking to describe and probe the role of nuclear organization in stem cell maintenance and differentiation
Our lab studies the relationship between form and function in the human nucleus, with the long term goal of describing the behavior of a dynamic system, the human genome, in stem cells and progenitors as they differentiate. We are specifically interested in inter- and intra-chromosomal associations as a function of lineage-restricted gene expression and linear gene arrangement. In addition, we investigate changes in genomic and nuclear organization in the context of human disease.
See Dr. Kosak's publications on PubMed.
Contact Dr. Kosak at 312-503-9582.
Understanding the mechanisms of neuronal dysfunction in neurodegenerative disorders that affect children and adults.
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.
View Dr. Krainc's full list of publications in PubMed.
Dimitri Krainc, MD, PhD
Ward Professor and Chairman
The Kume Lab’s research interests focus on cardiovascular development, cardiovascular stem/progenitor cells and angiogenesis.
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.
View Dr. Kume's publications on PubMed.
For more information, visit the faculty profile for Tsutomu Kume, PhD.
Contact Dr. Kume at 312-503-0623 or the Kume Lab at 312-503-3008.
Pediatric Fertility & Hormone Preservation & Restoration
Our research addresses fundamental regenerative medicine questions through the lens of reproductive biology. The main objective of our lab is to develop a patient-specific ovarian follicle niche that will support systemic endocrine function and fertility in women and girls who were sterilized by cancer treatments, have disorders of sex development or were exposed to other factors that could result in premature ovarian failure or sex hormone insufficiency. This research is a part of the Ann & Robert H Lurie Children’s Hospital Fertility and Hormone Preservation and Restoration Program that bridges basic science, translational research and clinical practice.
See Dr. Laronda's publications in PubMed.
Regulation of Motor Neuron and Dopaminergic Neuron Function in Development and Disease
Postdoctoral fellow jobs and graduate student rotation projects are available.
Research DescriptionSpinal 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.
View Dr. Ma's publications at PubMed
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
Our goal is to understand the integration of signaling and cytoskeletal dynamics on diverse developmental processes including centriole amplification, cell migration and cell polarity.
Centrioles are microtubule based structures with nine fold symmetry that are involved in both centrosome organization and aster formation during cell division. During the normal cell cycle centrioles duplicate once, generating a mother/daughter pair and in most post-mitotic vertebrate cells the mother centriole then goes on to form the basal body of a sensory cilium. Abnormalities in the duplication of centrioles (and centrosomes) are prevalent in many cancers suggesting a link between centriole duplication and cancer progression. We study what factors limit centriole duplication from a novel direction with the use of Xenopus motile ciliated cells. Ciliated cells are unique among vertebrate cells in that they generate hundreds of centrioles (basal bodies) therefore providing a great system for studying the regulation of centriole duplication. Understanding how nature has overcome the typically tight regulation of centriole duplication will lend insight into the molecular mechanisms of cancer progression.
Tissue development and homeostasis requires dramatic remodeling as new cells migrate into an epithelium. How migrating cells breakdown junctional barriers during development or during diseases processes such as metastasis is poorly understood at the molecular level. During the early development of Xenopus embryos, distinct cell types join the outer epithelium in a process called radial intercalation. We are interested in the molecular mechanisms that regulate both the migration of these cells as well as the tissue remodeling that occurs to accommodate them.
The ability of ciliated epithelia to generate directed fluid flow is an important aspect of diverse developmental and physiological processes including proper respiratory function. To achieve directed flow, ciliated cells must generate 100-200 cilia that are polarized along a common axis both within and between cells. My lab is currently working towards understanding the molecular mechanisms for how cell polarity is coordinated as well as how individual cilia interpret the cells polarity. We have determined that ciliated cells receive polarity cues via the non-cononical Wnt/Planar Cell Polarity (PCP) pathway, but the details of this are still poorly understood. Additionally, the PCP pathway is known to influence a cells cytoskeleton dynamics and a main goal is to understand how this influences the ability of individual cilia to coordinate their polarity.
See Dr. Mitchell's publications on PubMed.
Contact Dr. Mitchell at 312-503-9251.
Exploring how each specific cell type and organ acquires all its specific and unique morphological and functional characteristics during embryogenesis
The Oliver Lab focuses on understanding how each specific cell type and organ acquires all its specific and unique morphological and functional characteristics during embryogenesis. Alterations in the cellular and molecular mechanisms controlling organ formation can result in major defects and pathological alterations. Our rationale is that a better knowledge of the basic processes controlling normal organogenesis will facilitate our understanding of disease. Our goal is to dissect the specific stepwise molecular processes that make each organ unique and perfect. Our major research interests are the forebrain, visual system and the lymphatic vasculature and to address those questions we use a combination of animal models and 3D organ culture systems, stem cells and iPS cells.
Related to the lymphatic vasculature, our lab identified years ago the first specific marker for lymphatic endothelial cells and generated the first mouse model devoid of lymphatics. We have characterized many of the critical steps leading to the formation of the lymphatic vasculature. We have also reported that a defective lymphatic vasculature can cause obesity in mice and we are currently trying to determine whether this is also valid in humans.
In case of the central nervous system, our focus is to characterize how complex structures such as the forebrain and eye are formed. For that we have started to apply 3D organ culture systems derived from stem cell and iPS that allow us to grow eyes in a petri dish. Using this approach we expect to dissect the genes and mechanisms controlling these developmental processes.
View Dr. Olivers's publications at PubMed
Epigenetics of Stem Cells and the Stem Cell Niche
My lab focuses on how genetic and epigenetic modulators promote the development and maintenance of adult stem cells.
Microenvironments, or niches, support the maintenance of stem cells and facilitate the development of tumors through largely unknown mechanisms. Cell-autonomous genetic pathways and epigenetic networks have emerged as important determinants for the self-renewal and differentiation of stem cells in embryonic, juvenile and adult tissues. The importance of non-cell autonomous genetic and epigenetic factors is less well established. Our goal is to identify and characterize the genetic and epigenetic mechanisms utilized by both stem cells and their surrounding niche in supporting the stem cell program. For these studies, the developing mouse testis is used to examine interactions between male germline stem cells (GSCs) and their somatic niche.
Within the testis, differentiated germ cells are continually replenished by self-renewing GSCs to ensure the continuation of spermatogenesis throughout the lifetime of the male. GSCs are adult stem cells that develop after birth but which derive from embryonic primordial germ cells (PGCs). Under abnormal conditions, PGCs are thought to become pluripotent in vivo, develop into carcinoma in situ and form post-pubertal testicular germ cell tumors, the most common cancer in men aged 15-40. When GSC differentiation occurs at the expense of self-renewal, depletion of germ cells and infertility can result.
Several candidate factors influencing GSC self-renewal and differentiation are being studied: chromatin remodeling gene Sin3a, Polycomb group member Ezh2 and a chemokine ligand and its receptor, Cxcl12 and Cxcr4. Current research is examining the role of Sin3a in somatic Sertoli cells, which support GSCs and nurture all differentiating germ cells. Analysis of Ezh2 in GSCs as well as in testicular germ cell tumors is being conducted to determine whether an altered “Polycomb repression signature” promotes germ cell tumorigenesis. Characterization of Cxcl12, which is expressed in Sertoli cells, and Cxcr4, expressed in germ cells, is being performed to determine whether this chemokine signaling pathway is required to maintain GSCs in their niche and whether this mechanism involves non-coding microRNAs.
To achieve these aims, distinct testicular cell populations are separated by fluorescence- and magnetic-activated cell sorting and analyzed by transcriptional profiling. Potential SIN3A and EZH2 complex-bound target genes are identified by chromatin immunoprecipitation. Loss-of-function effects are examined by one of two methods: generation of conditional knockout mice or RNAi knockdown and transplantation of cultured GSCs into recipient testes. Future studies are aimed at understanding how the niche maintains stem cells and ensures proper organogenesis, with the possibility of tissue regeneration and cancer prevention as therapeutic applications.
For more information visit Dr. Payne's faculty profile page
View Dr. Payne's publications at PubMed
Oxygen sensing in embryonic development, tissue responses to hypoxia and tumor angiogenesis.
Our lab is interested in the molecular mechanisms of oxygen sensing and the importance of this process for embryonic development, tissue responses to hypoxia and tumor angiogenesis. We are testing the hypothesis that the mitochondria play a central role in detecting cellular oxygenation and signal the onset of hypoxia by releasing reactive oxygen species (ROS). These signals trigger downstream signal transduction pathways responsible for the transcriptional and post-translational responses of the cell. Transcriptional activation of genes by Hypoxia-Inducible Factor-1 confers protection against more severe hypoxia by augmenting the expression of glycolytic enzymes, membrane glucose transporters and other genes that tend to augment tissue oxygen supply by increasing the release of vascular growth factors such as VEGF, erythropoietin and vasoactive molecules that augment local blood flow. Current experiments are aimed at improving our understanding of how oxygen interacts with the mitochondrial electron transport chain to amplify ROS production and clarifying the targets that they act on to stabilize HIF and activate transcription.
In specific tissues, oxygen sensing is essential for normal function, but it can also contribute to disease pathogenesis. For example, during mammalian development, the lung tissue is hypoxic and blood flow is restricted in the pulmonary circulation in order to prevent escape of oxygen from the pulmonary capillaries to amniotic fluid. At birth, inflation of the lung with air causes an increase in lung oxygen levels, which triggers relaxation of pulmonary arteries. In Persistent Pulmonary Hypertension of the Newborn, failure of the pulmonary circulation to dilate results in elevated pulmonary arterial pressures and significant lung gas exchange dysfunction. We are testing the hypothesis that pulmonary vascular cells sense O2 at the mitochondria and that ROS released from those organelles trigger an increase in cytosolic calcium, which causes smooth muscle cell contraction. In adult patients with hypoxic lung disease, similar activation of hypoxic vasoconstriction can lead to chronic pulmonary hypertension, which can progress to right heart failure. A fuller understanding of the mechanisms of oxygen sensing in health and disease may lead to insights into therapeutic inhibition of this response in disease states.
In solid tumors, consumption of oxygen by highly metabolic tumor cells leads to hypoxia and threatens glucose supplies. Hypoxic tumor cells retain their oxygen sensing capacity and turn on expression of HIF-dependent genes, leading to tumor angiogenesis and increased blood supply, which permits further growth. We are currently exploring the hypothesis that the mitochondrial oxygen sensor is required for this response using pursuing genetic models. A better understanding of how tumor cells detect hypoxia could lead to the discovery of therapeutic approaches that would prevent detection of hypoxia and thereby prevent tumor progression.
For more information visit Dr. Schumacker's faculty profile page
View Dr. Schumacker's publications at PubMed
Development and regenerative repair of vertebrate limbs and hearts
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.
View all publications on PubMed
Phone Dr. Simon at 773-755-6391 or the Simon Lab at 773-755-6372.
Cell and molecular biology of herpesvirus invasion of the nervous system
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.
See Dr. Smith's publications on PubMed.
Contact Dr. Smith at 312-503-3745 or the lab at 312-503-3744.
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.
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.
View Dr. Sosa-Pineda's publications at PubMed
Morphogenetic processes in vertebrate embryo
Animal development requires proper specification of different cell types and, at the same time, their organization in to multicellular arrangements such as tissues and organs. My laboratory investigates the mechanisms that control morphogenetic processes in vertebrate embryo. We are studying these processes in the zebrafish (Danio rerio) using a combination of genetic analysis with embryological and molecular methods. The transparency of zebrafish embryos together with the generation of fluorescent transgenic animals allows us to use high-resolution confocal microscopy for in vivo analysis of cell behaviors. Moreover, similarities in developmental programs among all vertebrates make zebrafish an excellent model for investigating human diseases and development.
We are focusing current efforts on the mechanisms that shape the zebrafish head skeleton. We are particularly interested in the role of non-canonical Wnt signaling in cartilage morphogenesis. Mutants with altered non-canonical Wnt signaling pathways exhibit similar cell behavior defects during gastrulation and cartilage morphogenesis. This observation led to the hypothesis that non-canonical Wnt signaling controls cartilage element morphology by modification of chondrocyte behavior. My work on the characterization of the zebrafish knypek gene has revealed a new role for glypicans (heparan sulfate proteoglycan) in controlling morphogenetic movements during gastrulation by promoting non-canonical Wnt11 signaling. We are investigating the function of non-canonical Wnts and their potential co-receptors, glypicans, in chondrocyte differentiation and polarization. Because the initial steps in craniofacial development are similar in all vertebrates, these studies will help understand genetic basis for relatively frequent congenital anomalies causing abnormal development of the hard and soft tissue of the head and neck.
We are also interested in the developmental roles of other glypicans, as these extracellular proteins can play an essential role by interaction with growth factors, chemokines, extracellular matrix proteins, enzymes and enzyme inhibitors. Glypicans can be involved in regulation of ligand-receptor interactions and control of ligand distribution, both within a tissue and on the cell surface. For example, the clinical features of Simpson-Golabi-Behmel overgrowth syndrome, caused by mutation in the gene encoding Glypican 3, suggest that this protein is involved in regulation of cell survival and/or proliferation. One goal of my laboratory is to identify zebrafish glypicans and characterize developmental processes that they are regulating.
For more information view Dr. Topczewski's faculty profile page
View Dr. Topczewski's publications at PubMed
Organ and tissue engineering, 3D scaffold systems, induced pluripotent stem cells, stem and progenitor cell differentiation in 3D matrices, regenerative medicine applications
The major area of interest in my laboratory is advancing the state of art in organ regeneration and tissue engineering to develop methods to grow livers and kidneys as a cutting-edge solution to the organ shortage dilemma. Nationally, over 120,000 patients are waiting for solid organ transplantation, yet the number of transplants performed annually falls short of this need by 75%. In the absence of suitable donors for transplantation, organ failure leads to associated health problems, increased healthcare expenditures and death. Organ shortage is a national issue with local impact. In 2010 there were just over 1,050 solitary kidney, liver or heart transplants performed in Illinois, yet 311 patients in the state and more than 6650 nationwide died waiting for an organ.
Our research proposes a multidisciplinary solution to organ shortage by utilizing a tissue engineering approach to rehabilitate the extracellular matrix of organs that are not initially suitable for transplantation. Just-in-time organs, reconstituted with recipient derived progenitor cells, would abrogate the need for long waitlist times and associated waitlist mortality, reduce the reliance on organs from living donors and obviate the need for immunosuppression. Conceptually, these organs would be prepared from a donor matrix using a recipients own cells at the first signs of organ dysfunction. The re-engineered organ would then be ready for implantation when progressive organ failure indicates the need for transplantation.
The traditional paradigm in tissue engineering has been to grow cells on synthetic, polymer scaffolds to recreate the organ or tissue of interest. The limitation of this approach is the scale-up. Beyond a critical distance, diffusion of nutrients and oxygen is not sufficient to support cellular life and a vascular system must be incorporated into the tissue to supply nutrients. It has been technically difficult to design a synthetic micro-vasculature resembling small, terminal capillaries and to combine these structures with functional cells. Our approach challenges this paradigm by using the natural extracellular matrix as a scaffold to support the growth of new cells capable of repopulating the three-dimensional matrix. We have established protocols to remove parenchyma cells from livers and kidneys with a high efficiency of cellular removal and adequate retention of extracellular matrix molecules. We have further repopulated the vasculature of these matrix structures with endothelial cells derived from induced pluripotent stem cell technology. Together, we have partnered with the McCormick School of Engineering at Northwestern University and other leading academic and industrial centers to advance this fast moving field and address the problem of organ shortage.
View publications by Jason Wertheim at PubMed
Lab Phone 312-695-0257
Understand the development of the ovarian follicle, identify markers and determinants of egg quality and discover how this basic biology can be applied to patients.
Welcome to the Woodruff Lab, a team of research faculty, post-doctoral professionals, graduate students and lab technicians devoted to the study of ovarian health and development. We are working in three main areas. The first is ovarian follicle development, the study of the formation and maturation of the ovarian follicle, which is the basic functional unit of the ovary. The follicle includes somatic cells (which make hormones like estrogen and inhibin) and the oocyte (or egg). We are attempting to isolate the factors that regulate follicle and oocyte maturation and to understand the mechanisms of follicle and oocyte survival and death. The second focus of the Woodruff Lab is to develop in vitro follicle culture systems that can mimic the normal in vivo patterns of follicle development. The end goal of this research is to allow us to successfully remove healthy ovarian tissue from a cancer patient, safely store it until the patient has completed their treatment and then either harvest follicles from the tissue in an effort to grow them or surgically transplant the tissue to restore natural ovulation. Our third area of study is on the endocrine hormones inhibin and activin, which govern the reproductive cycle. Work on these hormones is essential to an understanding of healthy reproductive cyclicity and on the treatment of infertility.
View publications on PubMed.
Contact the Woodruff Lab via email.
Research Assistant Professor:
Molecular Mechanisms of Tumorigenesis and Cancer Metastasis
The Zhang laboratory is focused on two research directions: 1) determining role of tumor suppressors in development and cancer progression and 2) identifying immune components that control breast cancer metastasis.
The main focus of my research program is to study the roles of tumor suppressors in normal development and in breast and prostate cancer progression, focusing on maspin and an Ets transcription factor PDEF. Maspin is a unique member of the SERPIN family that plays roles in normal tissue development, tumor metastasis and angiogenesis. Genetic studies by my laboratory using maspin transgenic and knockout mice demonstrated an important role of maspin in normal mammary, prostate and embryonic development. Recently, we have identified several new properties of maspin. As a protein that is present on cell surface, maspin controls cell-ECM adhesion. This function is responsible for maspin-mediated suppression of tumor cell motility and invasion. We have also discovered that maspin is involved in the induction of tumor cell apoptosis through a mitochondrial death pathway. The long-term goals of these projects are to elucidate the molecular mechanisms by which maspin and PDEF control tumor metastasis and to identify their physiological functions in development. These analyses are not only important for basic biology and but also may lead to a therapy for cancer and other developmental diseases.
Another focus of research in Zhang lab is to identify immune components that control breast cancer metastasis. Chronic inflammation not only increases neoplastic transformation but also drives the inhibition of the immune response in a protective negative-feedback mechanism. Suppressive immune cells are recruited to the sites of inflammation and function to inhibit both innate and adaptive immune responses, enabling tumor tolerance and unmitigated tumor progression. To study the interplay between tumor and immune cells, the Zhang lab has developed a unique animal model of breast cancer that reproduces different stages of breast cancer bone metastasis. Molecules that control tumor-immune cell interaction and immunosuppression have been identified. We are currently studying roles of these genes in tumor-driven evolution that control chronic inflammation and immunosuppression. We hypothesize that these key pro-inflammatory genes are upregulated during cancer progression, which function synergistically to recruit and activate suppressive MDSCs, TAMs and Tregs, inducing chronic inflammation and an immunosuppressive tumor microenvironment conducive to metastatic progression.
For more information visit Ming Zhang's faculty profile.
View publications by Ming Zhang in PubMed
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.
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.
View publications by Youyang Zhao in PubMed.
For more information, visit Dr. Zhao's Faculty Profile page
Email Dr. Zhao
Contact Dr. Zhao’s Lab at 773-755-6355
Zhiyu Dai, PhD.
Research Assistant Professor
Xianming Zhang, PhD.
Research Assistant Professor
Narsa Machireddy, PhD.
Research Assistant Professor
Junjie Xing, PhD.
Colin Evans, PhD.
Varsha Suresh Kumar, PhD.
Xiaojia Huang, PhD
Hua Jin, PhD
Yi Peng, PhD
Mengqi Zhu, M.S.,