Research on the innate and adaptive immune responses in both health and disease.
All Labs in This Area
Role of mitochondria and metabolic processes in cancer growth, cardiac disease and immunological processes
Our lab focuses on three major areas of research:
Role of hexokinase enzymes in immune function, cancer growth and stem cell differentiation
Hexokinase (HK) enzymes phosphorylate glucose to trap it inside the cell. There are 5 mammalian HKs (named HK1-5), with two of them having a hydrophobic region at their N-terminus that allows them to bind to the mitochondria. We have made mouse models and developed in vitro systems to allow us to study the role of mitochondrial binding of HKs in glucose metabolism. We have determined that HK1 binding to the mitochondria determines whether glucose is used for anabolic processes (ie, pentose-phosphate pathway) or catabolism (ie, glycolysis). Thus, the non-enzymatic function of this protein and its subcellular location determines the fate of glucose. We are now studying this process in T-cells, vascular cells and cancer cells. We are also in the process of generating several mouse models of hexokinase enzymes, including HK2 without the mitochondrial binding domain and HK3 knockout mice. We will study these models in different disease and physiological conditions.
Characterization of cellular and mitochondrial iron regulation
Our lab has identified a novel mitochondrial protein, ATP-Binding Cassette-B8 (ABCB8), which plays a role in mitochondrial iron homeostasis and mitochondrial iron export. Mice with ABCB8 knocked out in the heart develop cardiomyopathy and mitochondrial iron accumulation. In addition, we have shown that a pathway involving mTOR and tristetraprolin, treatment with doxorubicin (an anticancer drug that also causes cardiomyopathy) and SIRT2 protein also impact cellular and/or mitochondrial iron regulation. Current studies in this area include: 1) further characterization of ABCB8 in iron homeostasis in other organs and disorders, 2) characterization of the mechanism for iron regulation by SIRT2, 3) identification of the mechanism by which mTOR is regulated by iron through epigenetic changes, 4) role of iron in viral infection, particularly HIV, 5) characterization of the effects of iron on mitochondrial dynamics and 6) identification of novel mitochondrial-specific iron chelators.
Role of mRNA-binding proteins in cellular and systemic metabolism
TTP is a protein that binds to AU-rich regions in the 3’ UTR of mRNA molecules and causes their degradation. It has been studied extensively in the field of inflammation. We recently showed that it also plays a role in cellular iron conservation. We have also shown that TTP is a key mediator of cellular metabolic processes. Our studies have demonstrated that TTP regulates glucose, fatty acid and branched-chain amino acid metabolism in the liver and muscle tissue. We also have evidence that TTP directly regulates mitochondrial electron transport chain (ETC) by targeting specific proteins in the ETC complexes. Finally, recent studies demonstrated that TTP also regulates systemic metabolism by targeting FGF-21 expression. We have both TTP Floxed mice (for the generation of tissue specific TTP knockout mice) and TTP knockout mice in the background of TNF-alpha receptor 1/2 knockout mice (to reduce the inflammatory burden). Current studies include: 1) role of TTP in liver metabolism of fatty acids and glucose, 2) effects of TTP on mitochondrial proteins, 3) mechanism of TTP regulation of branched-chain amino acid levels and 4) role of TTP in cardiac metabolism.
For more information, see Dr. Ardehali's faculty profile.
See Dr. Ardehali's publications in PubMed.
Transcriptional regulators of inflammation and metabolism
The burgeoning epidemic of obesity and type 2 diabetes mellitus presents a major health and therapeutic challenge. Transcriptional regulation is the fundamental control mechanism for metabolism, but a gap remains in our knowledge of gene regulatory pathways that control lipid and glucose homeostasis. Thus, we seek to identify modulable pathways that may be leveraged to counteract diabetes mellitus and its comorbidities, particularly cardiovascular disease. In this effort, we use a variety of genetic, molecular, next-generation sequencing, biochemical methods and physiological models. Our recent work has helped to reveal the genomic architecture for transcriptional regulation in innate immunity, which plays a key role in both diabetes mellitus and atherosclerosis. Surprisingly, although macrophage regulatory elements are often at significant linear distance from their associated genes, we identified interplay between transcriptional activators and repressors that is highly proximate, occurring at shared nucleosomal domains (Genes & Development, 2010). Moreover, we discovered a powerful role for the BCL6 transcriptional repressor to maintain macrophage quiescence and prevent atherosclerosis (Cell Metabolism, 2012).
Currently, we are exploring the impact of activator–repressor interactions on enhancer function and transcription, the signal-dependent control of repression and the functional impact of transcriptional activators and repressors on inflammatory and metabolic disease. In particular, we strive to further understand the role for B cell lymphoma 6 (BCL6), a C2H2-type zinc finger repressor, in innate immunity and metabolism.
In related work, we are developing new methods for cell-specific isolation of RNA and chromatin from tissues composed of mixed cell populations. These genetic tools will allow us to explore transcriptional regulation in living animals with unprecedented precision and global scope using transcriptome sequencing and ChIP-sequencing. We anticipate that these approaches will identify new candidate regulators and mechanisms underlying cardiovascular and metabolic disease.
For more information, please see Dr. Barish's faculty profile.
See Dr. Barish's publications in PubMed.
Understanding predispositions to allergic diseases
Research DescriptionThe question of primary interest in my lab is why only select individuals, despite being genetically similar and living in the same allergen environment, are prone to developing allergic disease, and which processes drive this predisposition? To address this, we employ a systems biology approach and bioinformatics to explore whether there is underlying unity in the pathogenesis of seemingly disparate allergic diseases. By synthesizing large volumes of biological data, we link departures from homeostatic conditions (including changes in metabolic, developmental, and endocrine systems) at the epithelial barriers of the skin, gut, and airways with innate immune system responses as a possible suite of mechanisms driving initiation of allergic disease. Specifically, we are asking the following questions: Are allergic diseases at different barrier sites caused by common systemic processes? Do hormones (estrogen, androgen, growth hormones) maintain homeostasis of the mucosal barriers? Why are developmental pathways for maintenance of tissue homeostasis linked to early susceptibility of asthma? What is the impact of environmentally relevant xenobiotics (xenoestrogens, aromatic hydrocarbons) on epithelial barriers and priming of allergic responses?
Secondarily, I keep being fascinated by a cell type that is intimately tied into mucosal biology, and plays central roles in many aspects of allergic disease - the eosinophil. I am intrigued by the fact that aside from being destructive in allergy, eosinophils play prominent roles in homeostasis and assist in normal development of tissues and maturation of other cell types – however, these alternate aspects of eosinophil biology remain largely unexplored. In my lab, we are studying the nature of reciprocal interactions between eosinophils and the mucosa in health and disease by asking the following questions: When and why are eosinophils homeostatic in the mucosa? What is their role in priming of immune responses?
For lab information and more, see Dr. Berdnikovs' faculty profile
See Dr. Berdnikovs' publications on PubMed.
Email Dr. Berdnikovs
The Bochner lab studies cells and siglec receptors (especially Siglec-8 and Siglec-F) involved in allergic inflammation, focusing mainly on eosinophils, mast cells and basophils in humans and mice.
Our primary research interests are in eosinophil- and mast cell-associated diseases, including asthma, hypereosinophilic syndromes and systemic mastocytosis. We have a particular interest and focus on understanding the function of Siglec-8, an inhibitory and sometimes pro-apoptotic receptor expressed on human eosinophils, basophils and mast cells and how it can be targeted for clinical benefit. Animal models are used to study its closest counterparts, such as Siglec-F. In studies involving carbohydrate biochemistry and glycoproteomics, the lab is isolating and characterizing potential glycan ligands for Siglec-F and Siglec-8. Finally, we are interested in food allergy and anaphylaxis and are exploring new ways to prevent allergic reactions in vitro and in vivo.
View lab publications via PubMed.
Email Dr. Bochner
Phone 312-503-0068 or the Bochner Lab at 312-503-1396.
Melanie C. Dispenza, MD, PhD
Piper Robida, PhD
Krishan Chhiba, BS
Yun Cao, MS
Research Lab Manager 1
Rebecca Krier, MS
Research Lab Manager 1
Jeremy O’Sullivan, PhD
Research Assistant Professor
Soon Cheon Shin, PhD
Mechanisms underlying sex-related differences in autoimmune disease; meningeal inflammation and how it impacts CNS degenerative disease
Mast cells are found in most tissues including the gastrointestinal tract, respiratory tract, pancreas, synovium, brain, spinal cord and the secondary lymphoid organs. Best studied in the context of allergic disease, the widespread location of mast cells, the plethora of inflammatory mediators they produce and their ability to directly interact with T and B cells made them good candidates for exacerbating the inflammation associated with autoimmune diseases such as diabetes, arthritis and multiple sclerosis (MS).
We have utilized KitW/Wv mice, which are mast cell deficient, to study the contribution of these cells in a rodent model of MS, Experimental autoimmune/allergic encephalomyelitis (EAE). EAE is characterized by the T cell mediated orchestration that damages myelin and myelin producing cells in the CNS leading to severe neurological deficits due to loss of normal nerve conduction. We have shown that mast cells in the meninges are activated early in this disease and promote the opening of the blood brain barrier (BBB), vasculature that is relatively impermeable and normally sequesters the CNS from the entry of inflammatory cells. Our current studies focus on understanding how these mast cells influence these events. In the process, we have established a new paradigm for the mast cell mediated inflammation of the meninges in immunity and believe this information will likely impact the understanding of other CNS diseases.
A second line of research investigates the development of mast cells from early myeloid precursors. Mast cells share a common precursor with a related cell type, basophils. While mast cells are resident in tissues and their numbers remain relatively stable, basophils are induced in high numbers in the blood only in certain infection settings. We have demonstrated the Ikaros, a transcription factor, is essential for proper mast cell development. In Ikaros deficient mice, mast cell development is aberrant and basophils predominate in the absence of inflammatory signals. We are studying the events that underlie mast cell basophil-lineage choice in development by examining the molecular targets of Ikaros and its mode of action under basal and infection conditions.
See Dr. Brown's publications on PubMed.
Contact Dr. Brown at 312-503-0108 or the lab at 312-503-1013.
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
The Chandel Lab studies the mitochondria as a signaling organelle; using reactive oxygen species as the primary signal for metabolic adaptation, differentiation and proliferation.
Historically, reactive oxygen species (ROS) have been thought to be cellular damaging agents, lacking a physiological function. Accumulation of ROS and oxidative damage have been linked to multiple pathologies, including neurodegenerative diseases, diabetes, cancer and premature aging. This guilt by association relationship left a picture of ROS as a necessary evil of oxidative metabolism, a product of an imperfect system. Yet few biological systems possess such flagrant imperfections, thanks to the persistent optimization of evolution. It appears that oxidative metabolism is no different. More and more evidence suggests that low levels of ROS are critical for healthy cellular function. This idea was first proposed in the mid-1990s when low levels of hydrogen peroxide (H2O2) were demonstrated to be important for cellular signaling. Although mitochondria were known to produce H2O2, NADPH oxidases (NOXs) were the subject of early study due to their well-described role as ‘dedicated H2O2 producers’ in phagocytes. We provided early evidence in the late 1990s that mitochondria release H2O2 to regulate the transcription factor hypoxia inducible factor 1 (HIF-1) (i.e. oxygen sensing). Subsequently, we showed that mitochondrial release of H2O2 can activate p53 and NF-κB. We have recently demonstrated that mitochondria-generated H2O2 can regulate other physiological processes including stem cell differentiation, adaptive immunity and replicative life span of mammalian cells. Furthermore, we have shown that cancer cells co-opt mitochondria-generated H2O2 to hyper-activate signaling resulting in tumor cell proliferation. There have been numerous reports from other laboratories in the past decade also highlighting the importance of mitochondrial H2O2-dependent signaling in metabolic adaptation, immunity, differentiation, autophagy and organismal longevity. We propose that mitochondrial release of H2O2 has evolved as a method of communication between mitochondrial function and other cellular processes to maintain homeostasis and promote adaptation to stress.
See Dr. Chandel's publications in PubMed.
Contact Dr. Chandel’s Lab at 312-503-1792
Genetic basis of inherited and acquired immunological disorders and skin cancer.
We employ cutting-edge genomics approaches to identify the genetic basis of inherited and acquired immunological disorders and skin cancer.
As an example, we have recently identified the genes and mutations underlying cutaneous T cell lymphoma, an incurable non-Hodgkin lymphoma of skin-homing T cells. The genes are components of the DNA damage, chromatin modifying, NF-kB and the T cell receptor signaling pathways. We are currently employing a comprehensive approach using human tissues and animal models to investigate the functions of these genes. We are confident these studies will allow us to elucidate the pathophysiology of this cancer and lead to the identification of novel therapeutic targets.
Work in the lab is funded by National Cancer Institute, Dermatology Foundation, American Skin Association and American Cancer Society. See the work of the Choi lab in the news. For further information, please also see Dr. Choi's faculty profile.
See Dr. Choi's publications on PubMed.
Contact Dr. Choi.
Pathogenesis of Legionella pneumophila and Stenotrophomonas maltophilia
L. pneumophila, the agent of Legionnaires' disease, is a classic environmental, opportunistic pathogen. The aim of our research is to characterize the bacterial genes and gene products that promote the occurrence of Legionnaires' disease.
S. maltophilia is an environmental gram-negative bacterium that is being increasingly associated with an array of human infections, including most notably pneumonia. The emergence of S. maltophilia as a significant health concern is due in part to its marked antibiotic resistance. Our lab has developed murine models of lung infection and is currently identifying virulence factors produced by this important new pathogen.
We employ a multi-faceted approach toward understanding the pathogenesis and natural history of bacterial infectious disease, with the hope that basic insights will lead to new methods of disease prevention, diagnosis, or treatment.
See Dr. Cianciotto's publications on PubMed.
Contact Dr. Cianciotto at 312-503-0385 or the lab at 312-503-1034.
Pathogenesis of human immunodeficiency virus (HIV)
The D’Aquila laboratory studies the pathogenesis of human immunodeficiency virus (HIV) persistence/latency and mechanisms of host “intrinsic” immune control of HIV replication. The long-term goal is to develop innovative strategies for a “functional cure” of HIV. We are developing novel interventions to induce sustained remissions after defined-duration antiretroviral therapy (ART). This includes bench-to-bedside research to characterize / leverage / increase APOBEC3 (A3) “intrinsic” immune defenses against HIV, diminish T cell activation-fueled HIV replication and innovate strategies to minimize latency/persistence of HIV.
In papers published in recent years, the D’Aquila laboratory proved that APOBEC3G and F are active in producer and target cells against wild-type (Vif-positive) HIV-1 at higher physiological levels of expression. Evidence was published that higher levels of A3G protein and activity contribute to the multiple mechanisms of spontaneous control of HIV-1 without ART seen in rare “elite controllers”. The laboratory has also identified that limiting c-Myc-dependent effects of the host T cell activation process limits early HIV replication in a way that may augment current virus-specific ART agents.
For more information, please see Dr. D'Aquila's faculty profile.
See Dr. D’Aquila's publications in PubMed.
Studying molecular networks in the regulation of immune response and autoimmunity
Our research goal is to identify the therapeutic molecular targets for the treatment of autoimmune diseases particularly of rheumatoid arthritis (RA) and type 1 diabetes (T1D).
In our laboratory, we use genetic, proteomic, molecular biology and immunological approaches to dissect the molecular networks underlying the regulation of immune response and autoimmunity. Several specific genes that are critical for immune regulation and autoimmune diseases have been identified in our laboratory. Small molecules that modulate the functions of these newly identified genes can potentially be used to treat type 1 diabetes and rheumatoid arthritis.
The current ongoing research projects, in my laboratory are:
1. Sirt1, a type-iii histone deacetylase, is required for immune tolerance.
2. The ubiquitin E3 ligase Synoviolin, is a therapeutic target for RA.
3. The tyrosine kinase c-Abl in T-cell differentiation and allergic lung inflammation.
4. The roles of RoxP3 in regulatory T cells.
5. Ubiquitination in aging and autoimmunity.
6. Novel microRNAs in immune tolerance and autoimmunity.
See Dr. Fang'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.
The Kato Lab investigates the mechanisms of initiation and amplification of type 2 inflammation in airway inflammatory diseases in humans.
The Kato Lab primarily focuses on the mechanism of type 2 inflammation in airway inflammatory diseases in humans. Currently, we use chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) as a model disease of type 2 inflammation. CRS is an inflammation of the nose and sinuses that blocks the air passages, causes headache and leads to loss of sleep, depression and reduced quality of life. CRSwNP which is a severe case of CRS, is well characterized by tissue eosinophilia with high levels of type 2 cytokines including IL-5 and IL-13. However, the mechanisms of type 2 inflammation in nasal polyps are still not well understood. The Kato Lab is currently focused on an epithelial-derived cytokine, TSLP (thymic stromal lymphopoietin), that is an IL-7-like cytokine molecule and is now recognized as an important regulator of type 2 inflammation in nasal polyps. We recently identified that TSLP is highly up-regulated in nasal polyps. TSLP is known to directly and indirectly induce type 2 inflammation via the activation of dendritic cells, Th2 cells, group 2 innate lymphoid cells (ILC2s) and mast cells which are all elevated in nasal polyps. My laboratory is currently investigating the role of Th2 cells, ILC2s, mast cells and dendritic cells in the amplification of type 2 inflammation and how TSLP contributes to type 2 inflammation through these cell types in nasal polyps. In contrast to CRSwNP, inflammatory patterns in non-polypoid CRS (CRSsNP) are much less understood. Recently, the PI’s laboratory fully characterized patterns of inflammatory cytokines in the nasal mucosa of control subjects and patients with CRS. We found that CRSsNP displays heterogenous inflammation and this heterogeneity in CRSsNP might be responsible for the inconsistency of results in CRSsNP-related studies. We are also currently working on understanding the effect of inflammatory endotypes on clinical phenotypes in CRSsNP.
See Dr. Kato's publications in PubMed.
For more information, view the faculty profile for Atsushi Kato, PhD.
Molecular Mechanisms Of Bladder Inflammation and Pelvic Pain
Our laboratory employs state-of-the-art cell culture and animal models to pursue multi-disciplinary projects in bacterial pathogenesis and neuro-immune interactions in a crippling pain syndrome. A key to our success is the rich training environment resulting from the close collaboration between clinical and basic scientists.
Urinary tract infection (UTI) is both a major medical issue and a fascinating problem of bacterial pathogenesis. We investigate all aspects of host pathogen interactions, from the immediate biochemical signaling evoked in bladder cells, to the associated inflammation, to the development of adaptive immune responses. We recently identified a novel signaling response of bladder cells induced by binding of uropathogenic E. coli (UPEC) that mediates the mutually exclusive processes of epithelial cell apoptosis and bacterial invasion of bladder epithelial cells; how this occurs is an active area of study. We have also identified a candidate live-attenuated UTI vaccine based on a UPEC mutant. We find that the UPEC mutant vaccine induces protective responses 100-fold greater than wild type UPEC. We are now determining the mechanism of this enhanced response by testing the hypothesis that the UPEC mutant skews the normal immune response and thus generates a more effective immunity.
Although pelvic pain can result from acute infection, interstitial cystitis (IC) is a debilitating chronic pelvic pain syndrome of unknown origin that is often considered a chronic bladder inflammation. We utilize a herpesvirus to induce an IC-like condition in mice Using this model, we have identified the mechanisms that result in both bladder pathophysiology and pelvic pain. Interestingly, while both pain and bladder damage require mast cell activation, pelvic pain results from the release of mast cell histamine, whereas bladder pathology is driven by mast cell release of tumor necrosis alpha (TNF). Current studies include the genetic basis of pain susceptibility, the spinal regulation of histamine and TNF release and the viral basis of pain. In addition, we recently were awarded a prestigious NIH center grant to study pelvic pain syndromes. The center award will extend our bladder pelvic pain studies to prostate- and bowel-associated pelvic pain and determine the mechanisms of pelvic organ crosstalk and signal integration in the spinal cord in mice. Our center collaborators will examine cortical and cognitive changes in pelvic pain patients using a combination of functional MRI and behavioral tests and develop novel quality-of-life tests to characterize pelvic pain non-invasively within populations. Thus, this center will illuminate pelvic pain mechanisms in clinical, epidemiologic and basic animal studies.
- Clemens JQ, Kutch JJ, Mayer EA, Naliboff BD, Rodriguez LV, Klumpp DJ, Schaeffer AJ, Kreder KJ, Clauw DJ, Harte SE, Schrepf AD, Williams DA, Andriole GL, Lai HH, Buchwald D, Lucia MS, van Bokhoven A, Mackey S, Moldwin RM, Pontari MA, Stephens-Shields AJ, Mullins C, Landis JR. The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS). Neurourology and Urodynamics. August 2020.
- Aguiniga LM, Searl TJ, Rahman-Enyart A, Yaggie RE, Yang W, Schaeffer AJ, Klumpp DJ. Acyloxyacyl hydrolase regulates voiding activity. American journal of physiology. Renal physiology. April 2020.
- Rosen JM, Yaggie RE, Woida PJ, Miller RJ, Schaeffer AJ, Klumpp DJ. TRPV1 and the MCP-1/CCR2 A. xis Modulate Post-UTI Chronic Pain. December 2018.
See Dr. Klumpp's publications in PubMed.
Translational and basic science projects that aim to develop new therapeutics for ocular angiogenesis independent of vascular endothelial growth factor (VEGF).
My research lab focuses on translational, basic science projects that aim to develop new therapeutics for ocular angiogenesis independent of vascular endothelial growth factor (VEGF). Neovascular age-related macular degeneration (nAMD) is the leading cause of visual impairment in the developed world. Currently, humanized anti-VEGF antibodies are the gold standard for the treatment of nAMD. Patients currently undergo frequent (up to monthly) injections of anti-VEGF antibodies into the vitreous cavity. The average patient achieves 1-2 lines of visual acuity gain, but 15% of patients still lose vision despite maximal anti-VEGF therapy. Although 15% appears small, given the high prevalence of nAMD, this amounts to 2.5 million patients worldwide. For these poorly responsive patients, there is a clear unmet need for alternative, VEGF-independent therapeutic options.
Macrophage recruitment is central in nAMD pathogenesis. Choroidal neovascularization (CNV) is the pathological hallmark of nAMD. In human histopathology studies of excised CNV membranes, macrophages are readily apparent. In mice, nAMD is modeled by laser-induced injury, which causes CNV membrane formation. Laser-induced CNV formation is robustly inhibited by chemical or genetic macrophage depletion. Based upon these accepted dogma, intravitreal steroids were attempted for nAMD treatment and are unfortunately ineffective. I hypothesize that steroids anti-inflammatory properties are too broad and specific anti-macrophage therapies are necessary. Furthermore, macrophages are highly plastic and heterogenous populations, including pro-inflammatory, pro-restorative, pro-fibrotic, and pro-angiogenic subtypes. My lab’s focus is to identify macrophage heterogeneity in CNV, delineate pro-angiogenic macrophage subtypes, and attempt to develop therapies against pro-angiogenic macrophages for nAMD.
For more information, visit the faculty profile for Dr. Lavine.
- A. Lavine, Y. Sang, S. Wang, M.S. Ip, N. Sheibani. “Attenuation of choroidal neovascularization by beta(2)-adrenoreceptor antagonism” (2013) JAMA Ophthalmology, 131(3):376-382. (PMID: 23303344)
- Nourinia, M. Rezaei Kanavi, A. Kaharkaboudi, S.I. Taghavi, S.J. Aldavood, S.R. Darjatmoko, S. Wang, Z. Gurel, J.A. Lavine, S. Safi, H. Ahmadieh, N. Daftarian, N. Sheibani. “Ocular safety of intravitreal propranolol and its efficacy in attenuation of choroidal neovascularization.” (2015) Investigative Ophthalmology and Visual Science, 56: 8228-8235. (PMID: 26720475)
- A. Lavine, M. Farnoodian, S. Wang, S.R. Darjatmoko, L.S. Wright, D.G. Gamm, M.S. Ip, N. Sheibani. “beta2-Adrenergic receptor antagonism attenuates CNV through inhibition of VEGF and IL-6 expression” (2017) Investigative Ophthalmology and Visual Sciences, 58 (1): 299-308. (PMID: 28114591)
- M. Hendrick, J. A. Lavine, A. Domalpally, A.D. Kulkarni, M.S. Ip. “Propranolol for proliferative diabetic retinopathy.” (2018) OSLI Retina, 49 (1): 35-40. (PMID: 29304264).
- A. Lavine, A.D. Singh, A. Sharma, K. Baynes, C.Y. Lowder, S.K. Srivastava. “Ultra-Widefield Multimodal Imaging in Primary Central Nervous System Lymphoma with Ophthalmic Involvement.” (2018) Retina, Epub ahead of print. (PMID 30044267)
Contact Dr. Lavine
Lab Phone: 312-503-0487
Immune recognition of melanoma-associated antigens, aiming to develop immunotherapeutics for benign and malignant disease.
Role for HSP70i in driving autoimmune responses. This stress protein is included as a component of some anti-tumor vaccines based on its chaperone and adjuvant functions. In human samples, we found that HSP70i is upregulated in vitiligo skin, that HSP70i can associate with melanosomes under stress and that the heat shock protein is increasingly secreted by vitiligo melanocytes.
Development of an immunotherapeutic vaccine for patients with lymphangioleiomyomatosis (LAM). This devastating disease involves development of slow growing tumors in the lungs of female patients with mutations in TSC1 or TSC2. As tumor cells of smooth muscle cell origin transdifferentiate to express melanoma associated antigens, we propose to target melanosomal antigens using T cell receptor transgenic, autologous T cells.
Development of a chemopreventive approach towards melanoma. The concept carries similarity to ‘elective surgery’ available for some other cancers. This strategy is further supported by the immune response that is indirectly elicited by dying melanocytes targeted by topically applied bleaching phenols. We have contributed to elucidating the mechanism by which phenolic agents can induce melanocyte death, expanded the arsenal of reagents to include those which specifically target the stem cell population and studied the immune response that follows.
Restoring tolerance in newly developed mouse models of autoimmune vitiligo. Contrary to the existing problem of overzealous regulatory responses that interfere with anti-tumor immunity, patients with autoimmune disease activity generally lack effective regulatory responses. So whereas anti-CD25 therapy to deplete Tregs is popular as a pretreatment for patients undergoing anti-tumor immunotherapy, the opposite holds true in autoimmune disease. We propose to manipulate Treg homing in particular, and recently demonstrated elevated CCR4 expression in circulating Treg from melanoma patients whereas its ligand is highly expressed in tumors; the opposite holds true in vitiligo.
For more information, see the faculty profile for Dr. Le Poole, PhD.
Epstein-Barr virus (EBV) and herpes simplex virus (HSV) entry, replication and pathogenesis.
Research in the Longnecker laboratory focuses on herpes simplex virus (HSV) and Epstein-Barr virus (EBV). These viruses typically cause self-limiting disease within the human population but both can be associated with serious complications. EBV is associated with variety of hematopoietic cancers such as African Burkitt lymphoma, Hodgkin Lymphoma and adult T-cell leukemia. EBV-associated lymphoproliferative disease occurs in individuals with congenital or acquired cellular immune deficiencies. The two notable epithelial diseases associated with EBV infection are nasopharyngeal cancer and oral hairy leukoplakia. Similar to EBV, HSV latent infections are very common in humans. HSV typically does not cause severe disease but is associated with localized mucocutaneous lesions, but in some cases can cause meningitis and encephalitis. The Longnecker laboratory focuses on several aspects of EBV and HSV replication and pathogenesis. First, the molecular basis EBV transformation and how it relates to cancer is being investigated. The laboratory is currently screening selective inhibitors that may be beneficial in EBV-associated cancers such as Hodgkin lymphoma, Burkitt lymphoma and proliferative disorders that occur in HIV/AIDS and transplant patients. Second, the laboratory is investigating herpesvirus latency in the human host and pathogenesis associated with infections in humans. In this regard, the laboratory is developing animal models for EBV and HSV infections. Finally, the laboratory is investigating the function of herpesvirus encoded proteins and the cellular receptors that are important for infection both using in vivo culture models as well as animal models. Ultimately, studies by the Longnecker laboratory may provide insight for the development of novel therapeutics for the treatment of herpesvirus infections in humans and better understanding of the herpesvirus life cycle in the human host
For lab information and more, see Dr. Longnecker's faculty profile
See Dr. Longnecker's publications on PubMed.
Contact Dr. Longnecker at 312-503-0467 or the lab at 312-503-0468 or 312-503-9783.
Investigating genetic and epigenetic changes in bladder cancer, as well as immuno-oncology in bladder cancer
The Meeks lab is investigating the epigenetics and genetic mutations associated with cancer biology. Specifically, he is studying how chromatin remodeling genes play a role in bladder cancer. In addition, he is investigating the “driver mutations found in bladder cancer. In the future, he hopes to develop novel systemic and intravesical therapies to improve survival of patients with bladder cancer.
- Meeks JJ, Robertson AG. Immune Signatures Dominate Molecular Subtyping to Predict Response to Neoadjuvant Immunotherapy. European Urology. June 2020.
- Robertson AG, Groeneveld CS, Jordan B, Lin X, McLaughlin KA, Das A, Fall LA, Fantini D, Taxter TJ, Mogil LS, Lindskrog SV, Dyrskjøt L, McConkey DJ, Svatek RS, de Reyniès A, Castro MAA, Meeks JJ. Identification of Differential Tumor Subtypes of T1 Bladder Cancer. European Urology. January 2020.
- Fantini D, Glaser AP, Rimar KJ, Wang Y, Schipma M, Varghese N, Rademaker A, Behdad A, Yellapa A, Yu Y, Sze CC, Wang L, Zhao Z, Crawford SE, Hu D, Licht JD, Collings CK, Bartom E, Theodorescu D, Shilatifard A, Meeks JJ. A Carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer. Oncogene. April 2018.
Refer to PubMed for a full list of publications.
Elucidation of mechanisms of pathogenesis and immune regulation of autoimmune disease, allergy and tissue/organ transplantation
The laboratory is interested in understanding the mechanisms underlying the pathogenesis and immunoregulation of T cell-mediated autoimmune diseases, allergic disease and rejection of tissue and organ transplants. In particular, we are studying the therapeutic use of short-term administration of costimulatory molecule agonists/antagonists and specific immune tolerance induced by infusion of antigen-coupled apoptotic cells and PLG nanoparticles for the treatment of animal models of multiple sclerosis and type 1 diabetes, allergic airway disease, as well as using tolerance for specific prevention of rejection of allogeneic and xenogeneic tissue and organ transplants.
For lab information and more, see Dr. Miller's faculty profile.
See Dr. Miller's publications on PubMed.
Contact Dr. Miller at 312-503-7674 or the lab at 312-503-1449.
Regulatory T cells in inflammation
The immune system is tightly controlled by multiple mechanisms, and Foxp3+ regulatory T (Treg) cells are prominent active regulators of immunity and tolerance. Defects in Treg cell generation or function result in uncontrolled systemic autoimmune inflammation. Despite extensive investigation in Treg cell biology, our understanding the mechanisms underlying Treg cell development and functions still remains incomplete. There is increasing evidence that Treg cell functions can be compromised under certain conditions, and such dysregulation is thought to be a contributing factor of chronic inflammatory conditions. Our laboratory studies both cellular and molecular factors that control Treg cell functions.
There are three major research projects currently underway in the laboratory.
1. IL-27 and Treg cells: Earlier studies had identified that IL-27, an immune regulatory cytokine produced by activated APCs, plays a non-redundant role in regulating Treg cell function. IL-27 acts on the IL-27 specific receptors (made of IL-27Ra and gp130 subunit) expressed on multiple cell types, primarily lymphocytes. Using various genetic approaches, our research focuses on identifying key source of IL-27 in autoimmune inflammation in the central nervous system and underlying mechanism by which IL-27 controls Treg cell function.
2. Glucocorticoids, miR-342, and Treg cells: We recently reported a novel role of Treg cells during glucocorticoid-induced treatment of chronic inflammation. In this study, we discovered a novel micro-RNA-342 molecule that is induced by steroid treatment in Treg cells and directly controls Treg cell metabolism. We are investigating the underlying mechanism by which this new micro-RNA-342 controls Treg cell function.
3. Lag3 and Treg cells: Lag3 is a new immune checkpoint molecule implicated in negatively regulating T cell functions. We discovered that Lag3 is induced by IL-27 stimulation in Treg cells and that Lag3 expression in Treg cells is critical for their suppressive function. We have generated several new mouse models in which Lag3 function and signaling pathways are targeted in a cell type specific manner. These novel animal models will allow us to dissect underlying mechanism of Lag3 in Treg cells and to identify potential therapeutic strategies not only to inhibit inflammation but also to enhance anti-tumor immunity by targeting Lag3 in Treg cells.
For lab information and more, see Dr. Min’s faculty profile.
See Dr. Min's publications.
Contact Dr. Min at 312-503-1805.
Focusing on the emigration of leukocytes across vascular endothelial cells in the process of inflammation
Most diseases are due to or involve a significant component of inflammation. My lab studies the inflammatory response at the cellular and molecular level. We are focused on the process of diapedesis, the "point of no return" in inflammation where leukocytes squeeze between tightly apposed endothelial cells to enter the site of inflammation. We have identified and cloned several molecules that are critical to the process of diapedesis (PECAM (CD31), CD99, and VE-cadherin) and are studying how they regulate the inflammatory response using in vitro and in vivo models. We have recently described the Lateral Border Recycling Compartment, a novel para-junctional organelle that contains PECAM and CD99 and is critical for diapedesis to occur. We are currently investigating how this compartment regulates diapedesis in the hope of finding novel and highly specific targets for anti-inflammatory therapy.
The “holy grail” of therapy is to develop selective anti-inflammatory agents that block pathologic inflammation without interfering with the body’s ability to fight off infections or heal wounds. By understanding how endothelial cells at the site of inflammation regulate leukocyte diapedesis, we are hoping to do just that. We have identified several molecules critical for diapedesis in acute and chronic inflammatory settings that can be genetically deleted or actively blocked to markedly inhibit clinical symptoms (e.g. in a mouse model of multiple sclerosis) and tissue damage (e.g. in a mouse model of myocardial infarction) without impairing the normal growth, development, and health of these mice. Our inflammatory models include atherosclerosis, myocardial infarction, ischemia/reperfusion injury, stroke, dermatitis, multiple sclerosis, peritonitis, and rheumatoid arthritis. We are also using 4-dimensional intravital microscopy to view the inflammatory response in real time in living animals.
- What are the molecular mechanisms and signaling pathways that endothelial cells use to regulate the inflammatory response?
- How can we therapeutically treat inflammatory diseases without compromising the ability of the immune system to respond to new threats?
- Do circulating tumor cells use the same mechanisms as leukocytes to cross blood vessels when they metastasize?
We have a high-resolution Perkin Elmer ULTRAVIEW Vox System spinning disk laser confocal microscope in the upright configuration on an Olympus BX51WI fixed stage in my laboratory designed for intravital microscopy. We can image the ongoing inflammatory response and response to our drugs in real time in anesthetized mice with unprecedented temporal and spatial resolutions. We presently image inflammation in the cremaster muscle, intestine, and brain.
Of interest to History of Science buffs, we have the original Zeiss Ultrafot II microscope used to film the first movies of neutrophils ingesting bacteria. As you might expect from something built by Zeiss in the first half of the 20th century, the optics are still fantastic and we use it in our daily work.
Recently we made two major discoveries in endothelial cell inflammatory signaling: Identification of TRPC6 as the cation channel responsible for the endothelial cell calcium flux required for transmigration and description of the CD99 signaling pathway. Both had eluded discovery for decades.
- Watson, R.L., J. Buck, L.R. Levin, R.C. Winger, J. Wang, H. Arase, and W.A. Muller. 2015. Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration. J. Exp. Med. 212:1021-1041.
- Weber, E.W., F. Han, M. Tauseef, L. Birnbaumer, D. Mehta, and W.A. Muller. 2015. TRPC6 is the endothelial calcium channel that regulates leukocyte transendothelial migration during the inflammatory response. J Exp Med 212:1883-1899. PMID: 26392222
- AAAS Fellow, elected 2010
- Rous-Whipple Award, American Society for Investigative Pathology, 2013
- Ramzi Cotran Memorial Lecture, Brigham and Women’s Hospital, 2014
- Karl Landsteiner Lecture, Sanquin Research Center, Amsterdam, Netherlands, 2016
- Member, Faculty of 1000 Leukocyte Development Section
- American Society for Investigative Pathology (ASIP) Council
- ASIP Research and Science Policy Committee Chair
- North American Vascular Biology Organization (NAVBO) Secretary-Treasurer
NIH R01 HL046849-26 William A. Muller 08/01/91 – 05/31/20
The Roles of Endothelial PECAM and the LBRC in Leukocyte Transmigration
This study investigates how PECAM-1 and the LBRC regulate transmigration. We will investigate how PECAM ligation on endothelial cells activates TRPC6 to promote the calcium flux necessary for transmigration (Aim I). We will identify how endothelial IQGAP1 regulates transmigration by regulating targeted recycling of the LBRC (Aim II). We will identify how kinesin light chain 1 variant 1 facilitates movement of the LBRC during targeted recycling (Aim III). All of these Aims include mechanistic studies in vitro and validation studies in vivo using mouse models of ischemia/reperfusion injury in acute inflammation and myocardial infarction.
NIH R01 HL064774-16 William A. Muller 04/01/00 – 08/31/20
Beyond PECAM: Mechanisms of Transendothelial Migration
This study investigates the role of PECAM, CD99L2, and CD99 in transendothelial migration. Aim I will test the hypothesis that leukocytes control the molecular order of transmigration by polarizing PECAM on their leading edge and CD99 on the trailing edge during transmigration. Aim II will identify the signaling mechanisms by which CD99L2 regulates transmigration. Aim III will identify the signaling mechanisms by which CD99 regulates targeted recycling of the LBRC and transmigration downstream of Protein Kinase A. All Aims have in vitro mechanistic studies and in vivo validation studies using intravital microscopy in the cremaster muscle circulation and a murine model of ischemia/reperfusion injury in myocardial infarction.
For more information, visit the faculty profile of William A Muller, MD, PhD
View Dr. Muller's publications at PubMed
Research Assistant Professors
- David Sullivan, PhD firstname.lastname@example.org
- Annette Gonzalez, PhD email@example.com
- Tao Fu, PhD firstname.lastname@example.org
- Ayush Batra, MD email@example.com
- Neil Nadkarni, MD firstname.lastname@example.org
- Prarthana Dalal (MD/PhD) PrarthanaDalal@u.northwestern.edu
- Nakisha Rutledge Rutledge2012@u.northwestern.edu
- Margarette Clevenger MargaretteClevenger2021@u.northwestern.edu
- Clifford Carpenter, PhD email@example.com
Office: Ward Building, Room 3-126
303 East Chicago Avenue
Chicago, IL 60611-3008
Phone: (312) 503-0436
Fax: (312) 503-8249
Lab: Ward Building 3-070 and 3-031
Lab Phone: (312) 503-5200
Lab Fax: (312) 503-2630
Immune regulation and vaccines
How can one improve immune responses during chronic infection or cancer? How can one improve the efficacy of viral vaccines? These are 2 main questions in the Penaloza lab. A unifying concept in the lab is how innate immune responses (TLRs and IFN-I) can be harnessed to treat immune exhaustion and improve vaccines.
Recently, the Penaloza group demonstrated a potent synergy between TLR4 signaling and PD-1 blockade at reinvigorating T cell function during chronic viral infection (Wang, PLOS Pathogens, 2019). This was the first demonstration that a specific microbiome component (LPS) can potentiate immune checkpoint therapy, via a B7 costimulation dependent mechanism. The group is now investigating whether other microbial components that target innate immune receptors can also improve immune checkpoint therapy, not only against chronic infections, but also against cancer. More recently, the Penaloza laboratory developed a novel strategy to improve viral vaccines by transiently blocking IFN-I (Palacio, JEM, 2020). Although IFN-I provides a rapid antiviral protection in the setting of natural infection, IFN-I can extinguish antigen prematurely following vaccination, impinging upon the priming of adaptive immune responses. By carefully downmodulating IFN-I at the time of vaccination, his group demonstrated an improvement in vaccine efficacy, using experimental HIV-1 and coronavirus vaccines.
Dr. Penaloza’s research has also investigated the mechanisms by which T regulatory cells suppress exhausted CD8 T cells (Penaloza-MacMaster, JEM, 2014), and how lack of these suppressive mechanisms can result in lethal immunopathology following viral infection (Penaloza-MacMaster, Science, 2015).
In summary, Dr. Penaloza's research is focused on immune regulation and vaccines, with a special emphasis on understanding how innate signals and immune checkpoints regulate adaptive immunity.
See Dr. Penaloza-MacMaster's publications on PubMed.
Contact Dr. Penaloza-MacMaster at 312-503-0357.
The Perlman Lab centers on rheumatic disease, particularly the impact that macrophages play in pathogenesis of rheumatic disease.
Macrophages have emerged as key players in the development of inflammation and fibrosis in central target organs including the synovium, kidney and lung during the pathogenesis and remission of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), respectively. Macrophages also contribute to the co-morbidities associated with these diseases including atherosclerosis and obesity. We observed marked heterogeneity in the macrophage population within diseased tissues that is dependent on their origin (embryonic vs. bone marrow derived), target organ and microenvironment. Moreover, these macrophages are extremely plastic and can alter their phenotype throughout the course of disease. Based on our data we developed a central hypothesis that during the initiation and early progression phase of disease tissue resident macrophages that normally function to maintain tolerance to local antigens, are overwhelmed by recruited pro-inflammatory or pro-fibrotic monocyte derived macrophages or pro-inflammatory dendritic cells depending on the target organ and environmental milieu. As the disease progresses to the chronic phase, however, the recruited macrophages acquire characteristics reminiscent of tissue resident macrophages while retaining a pro-inflammatory and pro-fibrotic phenotype, resulting in failed resolution of inflammation and progressive tissue destruction and fibrosis. The data anticipated from our projects would be the first to demonstrate a direct linkage of macrophage ontogeny and activation to disease activity and tissue damage. In addition, our studies allow us to explore commonalities in macrophage function between diseases that could lead to broad therapeutic interventions. In our state-of-the-art murine models we use cutting-edge technologies that we developed including micro-MRI, CT and SPECT to evaluate joint inflammation, bone destruction and lung fibrosis, Luminex-based gene arrays and multiparameter flow cytometry/sorting, whole population RNA seq and single cell RNA Seq and Chip-seq. We will cross-reference these data with those we will obtain through the AMP programs, which examine macrophage heterogeneity in the synovium and kidney from patients with rheumatic disease. This will allow us to rapidly move to functional analyses of relevant pathways and testing of new therapeutic strategies in the mouse models. I believe that our data has the potential to be paradigm shifting and transformative for the field of rheumatic disease.
View Dr. Perlman's publications at PubMed
For more information related to the Perlman Lab, or to connect with us, please see Harris R Perlman’s, PhD, profile.
Contact Dr. Perlman at 312-503-8003 or the Perlman Lab at 312-503-1933.
The lab of Dr. Marcus E. Peter studies various forms of cell death including apoptosis, which is a fundamental process to regulate homeostasis of all tissues and to eliminate unwanted cells specifically in the immune system.
Another interest lies in the study of RNA interference and based on toxic RNAs to development a novel form of cancer treatment.
View lab publications via PubMed.
Contact Dr. Peter at 312-503-1291 or the Peter Lab at 312-503-2883.
Research Assistant Professor
The Pope Lab studies the biology of macrophages in the pathogenesis of rheumatoid arthritis (RA). These studies are directed at defining the mechanisms that promote resistance to apoptosis or programmed cell death and the role of endogenous Toll Like Receptor (TLR) ligands in the pathogenesis of RA.
Our laboratory has identified the upregulation of the anti-apoptotic protein, Flice Like Inhibitory Protein (FLIP), during monocyte to macrophage differentiation. They have demonstrated that FLIP is highly expressed in the rheumatoid joint and is responsible for protecting RA macrophages from Fas-mediated apoptosis. These studies have been extended to examine the in vivo relevance of FLIP to macrophage biology. Mice with FLIP conditionally deleted in myeloid cells are not capable of developing macrophages. The relevance of these observations to chronic inflammatory arthritis is currently under investigation. Since macrophages are critical to the pathogenesis of RA, future studies will focus on macrophage specific FLIP as a therapeutic target in RA.
Additional studies in the laboratory are focusing on the role of endogenous TLR ligands as potential contributors to the persistent activation of macrophages in the RA joint. The Pope laboratory has identified an endoplasmic reticulum (ER) localized protein called gp96, which binds to TLRs within ER of macrophages and correctly transports them to the cell membrane or endosome. In patients with RA, gp96 is highly increased in RA synovial tissue, particularly in macrophages, and is found in RA synovial fluid in high concentrations. gp96 binds to the extracellular domains of TLR2 and TLR4. Both recombinant gp96 and gp96 present in the RA synovial fluid is capable of activating TLR2 and to a lesser degree TLR4. Ongoing studies in the laboratory are further characterizing the mechanisms by which gp96 and other endogenous TLR ligands might contribute to the pathogenesis of RA employing in vitro studies utilizing cells isolated from the joints of patients with RA and experimental murine models of RA
Additional studies are ongoing in the laboratory to further identify and define the potential clinical relevance of endogenous TLR ligands in the RA joint employing three approaches which are dependent upon binding to endogenous ligands to TLRs. These approaches include the use of recombinant IgG Fc-TLR2 and IgG Fc-TLR4 to pull down TLR ligands from cells isolated from the RA joint; the use of HEK-TLR2 and HEK-TLR4 cells to bind endogenous TLR ligands in RA synovial fluid which will be identified employing a proteomics approach and utilizing a yeast 2 hybrid system where mRNA from inflammatory RA synovial tissue has been employed to develop the bait, while the extracellular domains to TLR2 and TLR4 are being used as the prey. Each of these approaches have identified candidate molecules which are being further characterized for a potential role in the pathogenesis of RA.
View Dr. Pope's publications at PubMed
For more information related to the Pope Lab’s work, please see Richard M. Pope’s, MD, profile.
Contact Dr. Pope at 312-503-8003 or the Pope Lab at 312-908-1965
Calcium signaling, inflammation, and brain function
Research in the laboratory of Murali Prakriya, PhD, is focused on the molecular and cellular mechanisms of intracellular calcium (Ca2+) signaling. Ca2+ is one of the most ubiquitous intracellular signaling messengers, mediating many essential functions including gene expression, chemotaxis and neurotransmitter release. Cellular Ca2+ signals generally arise from the opening of Ca2+-permeable ion channels, a diverse family of membrane proteins. We are studying Ca2+ signals arising from the opening of store-operated Ca2+ channels (SOCs). SOCs are found in the plasma membranes of virtually all mammalian cells and are activated through a decrease in the calcium concentration ([Ca2+]) in the endoplasmic reticulum (ER), a vast membranous network within the cell that serves as a reservoir for stored calcium. SOC activity is stimulated by a variety of signals such as hormones, neurotransmitters and growth factors whose binding to receptors generates IP3 to cause ER Ca2+ store depletion.
The best-studied SOC is a sub-type known as the Ca2+ release activated Ca2+ (CRAC) channel encoded by the Orai1 protein. CRAC channels are widely expressed in immune cells and generate Ca2+ signals important for gene expression, proliferation and the secretion of inflammatory mediators. Loss of CRAC channel function due to mutations in CRAC channel genes leads to a devastating immunodeficiency syndrome in humans. Our goals are to understand the molecular mechanisms of CRAC channel activation, and their physiological roles especially in the microglia and astrocytes of the brain, and in the airway epithelial cells of the lung.
Despite the fact that CRAC channels are found in practically all cells, their properties and functions outside the immune system remain largely unexplored. In order to fill this gap, we have begun investigation of CRAC channel properties and their functions in two major organ systems: in the brain and the lung.
- In the brain, we are studying the role of CRAC channels for dendritic Ca2+ signaling in excitatory neurons of the hippocampus, and their role in synaptic plasticity and cognitive functions. We have found that CRAC channels formed by Orai1 are critical for amplifying glutamate receptor evoked calcium signals in dendritic spines of hippocampal neurons, and this step is essential for driving structural and functional measures of synaptic plasticity and cognitive processes involving learning and memory.
- In a second project, we are studying the role of CRAC channels in driving neuroinflammation. We have found that CRAC channels formed by Orai1 are essential for the production and release of proinflammatory cytokines and chemokines in microglia and astrocytes. We are examining the relevance of this pathway for mediating inflammatory and neuropathic pain.
- A third project is examining the role of CRAC channels for mediating pro- and anti-inflammatory processes in the lung. We have found that CRAC channels are a major mechanism for mobilizing Ca2+ signals in lung epithelial cells, and the downstream production of both pro- and anti-inflammatory mediators. We are examining the relevance of this signaling for lung inflammation in the context of asthma.
See Dr. Prakriya's publications on PubMed.
Contact Dr. Prakriya at 312-503-7030.
The Schleimer Lab investigates molecular and cellular mechanisms underlying pathogenesis of Chronic Rhinosinusitis and actions of anti-inflammatory steroids. We have a collaboration of bench scientists, Clinical Allergists and ENT surgeons.
Our group studies Chronic Rhinosinusitis, a disease of the nose and sinuses that affects over 30 million Americans. Using tissue samples collected from patients undergoing surgery for Chronic Rhinosinusitis through our close collaboration with Clinical Allergists and ENT surgeons, we study the gene and protein expression profiles as well as resident immune cell populations that are altered in disease in order to identify and explore potential mechanisms of disease progression and identify targets for therapeutic development. This work has provided evidence of dysregulation of epithelial immune barrier function, innate immunity, fibrin deposition and adaptive immune responses as potential mechanisms of disease progression. In the realm of epithelial barrier, we are currently investigating the mechanism by which Oncostatin M drives epithelial barrier degeneration. Additional research in our lab is pursuing mechanisms of fibrin deposition and the contributions of alterations in the fibrin system to polyp formation. Other experiments are working to reveal the potential impact of abnormal B cell activation in polyps. Finally, we continue our long running exploration of the cellular and molecular mechanisms of anti-inflammatory actions of glucocorticoid steroids and the causes of apparent steroid resistance in selected individuals and diseases.
View Dr. Schleimer's publications at PubMed
For more information, visit the faculty profile of Robert Schleimer, PhD.
Contact Dr. Schleimer at 312-503-0076
Senior Research Technician
Senior Research Technician
Monocyte and microglia interaction in the etiology and evolution of traumatic brain injury-induced neurodegeneration
Exploring respiratory failure
The Singer Lab focuses on determinants of resolution and repair of acute lung inflammation and injury. Our ultimate goal is to unravel the factors controlling resolution and repair and exploit those factors as therapies for acute respiratory distress syndrome (ARDS)—a devastating disorder responsible for the deaths of tens of thousands of people each year.
View Dr. Singer's publications on PubMed.
Email Dr. Singer or contact at 312-908-8163.
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.
Contributions of immune cell-mediated inflammation to development and progression of colorectal cancers
Immune cells are critical for host defense, however immune cell infiltration of mucosal surfaces under the conditions of inflammation leads to significant alteration of the tissue homeostasis. This includes restructuring of the extracellular matrix and alterations in cell-to-cell adhesions. Particularly, immune cell-mediated disruption of junctional adhesion complexes, which otherwise regulate epithelial cell polarity, migration, proliferation and differentiation can facilitate both tumorigenesis and cancer metastasis. Our research thus focuses on understanding the mechanisms governing leukocyte induced tissue injury and disruption of epithelial integrity as potential risk factors for tumor formation, growth and tissue dissemination.
Ronen Sumagin, PhD
Assistant Professor in Pathology
The Thorp laboratory studies how immune cells coordinate tissue repair and regeneration under low oxygen, such as after a heart attack.
The Edward Thorp Lab studies the crosstalk between immune cells and the cardiovascular system and, in particular, within tissues characterized by low oxygen tension or associated with dyslipidemia, such as during myocardial infarction. In vivo, the lab interrogates the function of innate immune cell phagocytes, including macrophages, as they interact with other resident parenchymal cells during tissue repair and regeneration. Within the phagocyte, the influence of hypoxia and inflammation on intercellular and intracellular signaling networks and phagocyte function are studied in molecular detail. Taken together, our approach seeks to discover and link basic molecular and physiological networks that causally regulate disease progression and in turn are amenable to strategies for the amelioration of cardiovascular disease.
View Dr. Thorp's publications at PubMed
Contact the Thorp lab at 312-503-3140.
Xin-Yi Yeap, MS
Lab Manager and Microsurgery
Studying benign prostate diseases, chronic prostatitis/chronic pelvic pain syndrome
The focus of research in the laboratory is to understand the pathogenesis of genitourinary diseases with emphasis on benign prostate disease in humans. Inflammation is a significant finding in a variety prostate diseases including prostatitis, BPH and prostate cancer. We study microbial and autoimmune mediated inflammation and innate and adaptive immune mechanisms in prostate disease. A particular area of interest is chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), a debilitating medical condition characterized by dysuria and pain. Projects in the lab use a combination of in vitro studies, animal models and clinical specimen assays to examine questions of interest such as the role of chemokines and T-cells in chronic pelvic pain.
For more information, see the faculty profile of Praveen Thumbikat, PhD.
- Liu Z, Murphy SF, Huang J, Zhao L, Hall CC, Schaeffer AJ, Schaeffer EM, Thumbikat P. A novel immunocompetent model of metastatic prostate cancer-induced bone pain. Prostate. July 2020.
- Roman K, Hall C, Schaeffer AJ, Thumbikat P. TRPV1 in experimental autoimmune prostatitis. Prostate. January 2020.
- Bell-Cohn A, Mazur DJ, Hall C, Schaeffer AJ, Thumbikat P. Uropathogenic escherichia coli-induced fibrosis, leading to lower urinary tract symptoms, is associated with type 2 cytokine signaling. American Journal of Physiology - Renal Physiology. April 2019.
View Dr. Thumbikat's publications at PubMed
Research in our laboratory focuses on the mechanisms of fibrosis and inflammation/autoimmunity in human diseases.
Our research integrates genetic and genomic approaches with experimental studies using cell-based systems, organ cultures and animal models. In particular, we are studying regulation of fibroblast activation, mesenchymal cell differentiation and the cross-talk between macrophages, monocytes and stromal cells and the role of innate immune signaling, in aberrant tissue remodeling and wound healing.
Fibrosis is a non-specific response that occurs in reaction to any type of chronic or persistent tissue injury. While acute fibrogenesis is beneficial for rapidly restoring tissue homeostasis and regeneration, chronic or deregulated responses to injury lead to scar. Fibrosis is now one of the a leading causes of deaths worldwide. Therefore, an important goal is to define the cells, metabolic states, molecules and signaling pathways that regulate tissue repair and how genetic and epigenetic modifications in these pathways result in chronic fibrosis. We focus on fibrotic diseases affecting the skin, lungs and heart.
We are investigating the molecular mechanisms that control activation of fibroblasts and myofibroblasts and the role of innate immunity, toll-like receptors and related pattern recognition receptors and the cross-talk among monocytes, macrophages, dendritic cells and adipocyte progenitor cells and mesenchymal stromal cells. In addition, studies are investigating the origins of activated stromal cells, using transgenic lineage tracing approaches. We focus on pathways implicated in large-scale genetic studies are candidates based on their association with scleroderma, pulmonary fibrosis and chronic inflammation.
We routinely employ molecular, cellular, biochemical and genetic approaches in our studies, along with omics approaches such as genomewide transcriptomics and GWAS, proteomics and candidate gene approaches. We make extensive use of human samples such as skin biopsies, lung tissue, explanted fibroblasts and blood cells and animal models of disease. We are also developing organoid approaches to model fibrosis and repair in human skin. Many of our studies focus on the discovery of targeted therapies and of biomarkers for predicting disease severity, activity and response to therapy in genetically diverse human populations.
View Dr. Varga's publications at PubMed
For more information visit Dr. Varga's faculty profile page
Contact Dr. Varga at 312-503-8003 or the Varga Lab at 312-503-0498
Studying malignant glioma, with a special emphasis on glioblastoma; pursuing incurable pediatric brain tumors and metastatic tumors that invade the brain/spinal cord.
Our laboratory utilizes DNA sequencing, gene expression profiling, proteomic analyses, flow cytometric methodology and many other basic techniques to pursue goals that are ultimately translatable for improving health and overall survival in patients with brain cancer. Although our research is primarily focused on malignant glioma, with a special emphasis on glioblastoma, we are also interested in pursuing incurable pediatric brain tumors, as well as metastatic tumors that invade the brain/spinal cord. It is our sincere hope that the basic mechanistic investigations that we carry out will uncover important and meaningful discoveries that translate into highly effective immunotherapeutic modalities for the benefit of patients with incurable cancer in the brain.
Please see Dr. Wainwright's publications in PubMed.
Contact Wainwright Lab
Contact the Wainwright Lab at 312-503-3161 or visit us on campus in Tarry 2-703.
Defining the molecular mechanisms of breast tumor initiation, progression, and metastasis, and identifying novel targets for therapeutic development.
The overarching goal of Wan laboratory is to define the molecular mechanisms of breast tumor initiation, progression, and metastasis, and to identify novel targets for therapeutic development. Particularly, the laboratory seeks to address how defects in the ubiquitin-proteasome system and other posttranslational modifiers such as protein methyltransferase, poly (ADP-ribose) polymerase and glycosyltransferase would result in genomic instability, deregulated tumor immune checkpoint function, abnormal cell cycle, and aberrant signaling that predispose otherwise normal cells to become cancerous tumor cells or promote cancer progression and metastasis. The research approaches in Wan laboratory include biochemical, cell biological, genetic, protein structural analyses as well as the use of breast cancer animal models and analyses of clinical specimens.
- Pharmacological suppression of B7-H4 glycosylation restores antitumor immunity in immune-cold breast cancers.2020. Cancer Discovery (in press)
- EIF3H Orchestrates Hippo Pathway-Mediated Oncogenesis via Catalytic Control of YAP Stability. PMID: 32269044
- A novel strategy to block mitotic progression for targeted therapy. PMID: 31669221
- A novel small-molecule antagonizes PRMT5-mediated KLF4 methylation for targeted therapy. PMID: 31101597
- Posttranslational Modifications in Tumor Immunity and Immunotherapy
- Posttranslational Modifications in Genome Stability and Carcinogenesis
- Posttranslational Modifications in Oncogenic Signaling and Tumor Invasion
- Posttranslational Modifications in Mitotic Regulation and Tumorigenesis
- Anticancer Drug Development
See Dr. Wan's publications on PubMed.
Contact Dr. Wan at 312-503-2769.
Research assistant professor:
Antigen Presentation, T-Cell Development and Regulation, Infectious Diseases and Autoimmune Diseases
Our lab focuses on two of the MHC class Ib molecules, H2-M3 and CD1. These molecules have unusual binding specificity for antigens that are conserved in bacteria. H2-M3 presents N-formylated peptides to cytotoxic T cells while CD1 presents lipid antigens to several distinct subsets of T cells. The high degree of conservation of these microbial antigens combined with the limited polymorphism of M3 and CD1 make these two molecules attractive targets for T-cell based vaccines against intracellular pathogens for a genetically diverse population. We have generated several animal models to examine the roles of M3 and CD1 in T cell development, autoimmune diseases and defense against infectious agents, including Listeria monocytogenes and Mycobacterium tuberculosis. Using these model systems, we study the mechanisms that regulate the selection and in vivo function of M3-restricted and CD1-restricted T cells. Additionally, these models are used to characterize novel microbial antigens recognized by MHC class Ib-restricted T cells. Studies on this relatively uncharacterized segment of the mammalian immunologic repertoire may lead to improved methods for vaccination against infectious diseases.
For lab information and more, see Dr. Wang's faculty profile.
See Dr. Wang's publications on PubMed.
Contact Dr. Wang at 312-503-9748 or the lab at 312-503-1093.
Computational immunology - Using genomic approaches to study rheumatic disease.
The goal of the Winter Lab of Functional Genomics is to apply genomic approaches to study rheumatic disease. Led by Dr. Deborah Winter, a computational immunologist, we employ the latest technologies for assays, such as RNA-seq, ChIP-seq, ATAC-seq and single cell expression, to profile the transcriptional and epigenomic profiles of immune cells in health and disease. Our goal is to define the underlying regulatory networks and understanding how they respond to challenge, illness and injury. We are particularly interested in the role of macrophages in diseases such as scleroderma, rheumatoid arthritis and lupus. Previous research has addressed the impact of the tissue environment on resident macrophages and the role of microglia, CNS-resident macrophages, in brain development. Our research combines molecular and systems biology, biotechnology, clinical applications and computer science. We use both mouse models and patient samples to help us understand and test different systems. We are committed to high standards of analysis and are continually updating and training in innovative computational techniques. We are currently recruiting highly motivated individuals to join the lab.
For more information, visit the faculty profile of Dr. Winter.
View Dr. Winter's publications at PubMed
Contact Dr. Winter at 312-503-0535 or by email.
Understanding the mechanisms of cancer immune evasion and development of novel immune therapy
Dr. Wu's research focuses on understanding the very fundamental questions of cancer development and progression with the ultimate goal to translate our knowledge into clinics. Dr. Wu’s laboratory is interested in specific aspects of Onco-immune interaction and cancer biology:
- Mechanisms of cancer immune evasion and development of novel cancer immunotherapy with specific focus on the NKG2D signaling pathways
- Inflammation and cancer with focus on understanding the role of the proinflammatory cytokine IL-6 in cancer initiation and progression
- Cancer biomarker discovery with focus on identifying biomarkers to distinguish progressive vs. indolent prostate cancer and to biomarkers to predict cancer patients at large who will be the better responders to immune checkpoint therapy
For more information please view the faculty profile of Jennifer Wu, PhD.
- Basher F, Dhar P, Wang X, Wainwright DA, Zhang B, Sosman J, Ji Z, Wu JD. Antibody targeting tumor-derived soluble NKG2D ligand sMIC reprograms NK cell homeostatic survival and function and enhances melanoma response to PDL1 blockade therapy. J Hematol Oncol. June 2020.
- Zhang J, Larrocha PS, Zhang B, Wainwright D, Dhar P, Wu JD. Antibody targeting tumor-derived soluble NKG2D ligand sMIC provides dual co-stimulation of CD8 T cells and enables sMIC + tumors respond to PD1/PD-L1 blockade therapy. J Immunother Cancer. August 2019.
View a full list of publications by Jennifer Wu at PubMed
Email Jennifer Wu, or phone at 312-503-1521
The Zhang Lab investigates the tumor-induced immune suppression.
Dr. Zhang’s laboratory work is focused on understanding the mechanisms of tumor-induced immune evasion. The overall goal is to develop novel and feasible strategies to improve cancer immunotherapy. He has been recently interested in the tumor microenvironment complexity whereby CD73 functions as an ecto-enzyme to produce extracellular adenosine, which limits anti-tumor T cell immunity. He is exploring the detailed mechanisms of CD73 by which the tumors evade the immune system using a combination of molecular, biochemical and mouse genetic approaches and to accomplish the targeted elimination of CD73 as a novel means to enhance cancer immunotherapy. Other ongoing studies involve: (1) Analyze the contribution of new key molecules including microRNAs from the perspective of cancer immunology in regulating regulatory T cells and/or myeloid derived suppressive cells; (2) Define a novel use of pre-existing chemotherapy drugs to overcome tumor-mediated immunosuppression; (3) Characterize the role of novel molecules in tumor T cell immunity and autoimmunity; (4) Understand the differential immune regulation in GVHD vs. GVL; and (5) Develop new animal models that can be employed in preclinical studies to most reflect human clinical trials.
View lab publications via PubMed.
For more information, visit the faculty profile page of Bin Zhang, MD/PhD.
Contact Dr. Zhang at 312-695-6180 or the Zhang Lab at 312-503-2435.
Donye Senon Dominguez
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 Zhang Lab investigates molecular/cellular MR imaging and functional imaging guided immunotherapy.
Dendritic cells (DCs) are the most potent antigen-presenting cells and tumor antigen-loaded DCs (DC-vaccines) can activate tumor-specific cytotoxic T lymphocytes in lymphatic tissues. DC vaccine immunotherapy has demonstrated great potential for the systemic treatment of cancers, but the clinical outcomes of DC-vaccine studies have been extremely variable. We will pay attention to DC-based vaccination induced tumor apoptosis and how that can affect treatment outcomes. The efficacy of DC-vaccines is strongly influenced by their ability to migrate to the draining lymph nodes (LNs). Therefore, visualization of in vivo DC-vaccine migration to the draining LNs should help predict therapeutic response. We propose that magnetic labeling of DC-vaccines will permit magnetic resonance imaging (MRI) of biodistribution. We will develop and optimize quantitative MRI-guided DC vaccination for PDAC therapy. This project will be carried out in a well-established transgenic KPC mouse model of PDAC (LSL-KrasG12D-LSLTrp53R172H-Pdx-1-Cre) that mimics both the genetic and histologic changes observed in human pancreatic cancer.
For more information, visit the faculty profile page of Zhuoli Zhang, MD/PhD.
Email Dr. Zhang
Phone Dr. Zhang at (312) 926-3874
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.,