Marlene Bouvier, Associate Professor, Ph.D.

McGill University, Montreal, Canada, 1988

Our research activities are focused on investigating the central role that class I major histocompatibility complex (MHC) molecules play in the immune system.

More specifically, we are studying the molecular and mechanistic basis of the class I antigen presentation pathway. The cell-surface presentation of antigens by class I MHC molecules is the culmination of a complex process that takes place in the endoplasmic reticulum (ER) and involves the specialized proteins tapasin (TPN), calreticulin (CRT), ERp57, and the transported associated with antigen processing. In the last few years, we have characterized the biochemical and biophysical properties of TPN, CRT, and ERp57 to better understand their roles and modes of action within the class I assembly complex. More recently, we have elucidated the mechanistic basis by which TPN modulates the selection of antigens that bind onto class I molecules. Ultimately, this selection process critically influences cellular immune responses.

Given that the class I antigen presentation pathway is the first line of defense against viral infections and malignant transformations, it is not surprising that human viruses have evolved sophisticated strategies to downregulate the expression of class I molecules at the cell surface and suppress the recognition of viral antigens by cytotoxic T cells. Thus, another area of interest in our laboratory is to study the molecular basis of viral immune evasion mechanisms that operate by interfering with the class I antigen presentation pathway.

Ananda Chakrabarty, Distinguished University Professor, Ph.D.

University of Calcutta (India), 1965.

The ability of certain infecting pathogenic bacteria to allow tumor regression in human patients has been known for more than hundred years, but the reason for regression was thought to be due to the production of cytokines and chemokines by an activated immune system.  We have shown that bacteria such as Pseudomonas aeruginosa produce a protein called azurin that is secreted when the bacteria are exposed to cancer cells.  Azurin enters preferentially to cancer cells than normal cells.  Unlike anticancer drugs that target a specific step in the cancer progression pathway, azurin, and a modified form of azurin called Laz produced by Neisserial species, target multiple steps in the cancer progression pathways, thereby interfering in cancer growth both in vitro and in vivo.  Azurin and Laz are also highly effective in forming complexes with various surface proteins of the malarial parasite Plasmodium falciparum and the AIDS virus HIV-1, thereby significantly inhibiting their growth.  Thus a single protein such as azurin or Laz might have potential therapeutic application against such unrelated diseases as cancer, malaria or AIDS, including coinfection of AIDS patients by the malarial parasite.  The structural similarity of the proteins such as azurin with the immunoglobulin folds may explain the broad range of activity of the bacterially derived azurin or Laz.

Zheng W. Chen, Professor and Director, M.D., Ph.D.

Peking Union Medical College (now Tsinghua University) 1988

Dr. Chen’s lab focuses on understanding of T cell immunobiology relevant to disease pathogenesis, immunotherapeutics and vaccines for HIV/AIDS, tuberculosis, AIDS-related tuberculosis, and recently malaria, plague and smallpox. The recent work from his lab and others has generated a new concept that

Vγ2Vδ2+ T cells, the major γδ T cell subpopulation in humans and nonhuman primates, belong to non-classical T cells with both innate and adaptive immune features, and contribute to immunity against tuberculosis. The ongoing studies at Dr. Chen’s lab are aimed to elucidate antigen presentation, TCR recognition, mucosal versus systemic responses and effector function of Vγ2Vδ2+ T cells, as well as their interaction with other immune cells. Dr. Chen’s lab is also leading the research efforts that target these γδ T cells for immunotherapeutics and vaccines against various infectious diseases including HIV/AIDS, tuberculosis, and malaria.

Another major research endeavor at Dr. Chen’s lab is to utilize the state-of-the-art vaccine technology to develop non-needle recombinant vaccines against HIV/ADIS, tuberculosis, malaria and other diseases relevant to biodefense. Dr. Chen’s lab has recently developed three non-needle vaccine platforms based on recombinant bacterial and viral vectors, and now is assessing these vaccine constructs for mucosal vaccination, immunogenicity and vaccine-induced immunity.

Dr. Chen’s lab has recently expanded its research programs and developed innovative nanotechnology-based methods to study nano-medicine and nano-immunology. Nanotechnology generally deals with physics and chemistry or material engineering, and is now emerging as multi-discipline superpower to advance life science and medicine. Dr. Chen’s lab has been utilizing the novel nanotechnology for dissecting immune molecules in T effector cells and their interactions with microbes at nanoscale.

Nancy Freitag , Professor, Ph.D.

University of California at Los Angeles, 1989.

In my lab we study the intracellular bacterial pathogen Listeria monocytogenes as a model system for understanding how pathogenic intruders survive within infected host cells. L. monocytogenes can cause life-threatening diseases in immunocompromised individuals, pregnant women, and neonates, and we are interested in determining how the bacterium determines its cellular location within infected hosts and regulates virulence gene expression.On the host side, we are working to elucidate the host cell defenses that serve to limit bacterial survival. We are also interested in using L. monocytogenes as an intracellular delivery system to explore the function of gene products delivered into the cytosol by other intracellular parasites in order to identify host cell targets and virulence factor function.

Bin He, Associate Professor, Ph.D.

Purdue University, 1993.

Our laboratory studies virus infection and innate immunity.  We are interested in virus-host interactions in relation to cytokine expression, cell signaling, and pathogenesis.  We investigate how viruses trigger or abate innate immune responses, with a focus on Toll-like receptor and cytosolic receptor pathways.   By taking molecular, cellular, genetic and systems biology approaches we aim to understand the interplay of viral and host factors involved in infectious and inflammatory diseases.

William Hendrickson, Associate Professor, Ph.D.

Tufts University, 1981.

I currently devote all my effort leading research core services for the university. I am Director of the Research Resources Center, which is part of the Office of the Vice Chancellor for Research. The RRC is comprised of 20 research cores and service units with 65 employees. I am also Director of Translational Technologies and Resources for the UIC Center for Clinical and Translational Sciences and Assistant Director of the UI Cancer Center. Most recently, I have devoted part of my effort in developing a $2.5M High Performance Computing Resource for UIC that is used for molecular modeling, engineering, imaging and genomics. My past interests were in basic molecular genetics of E. coli, specifically the transcription regulation mechanism of the L-arabinose operon. In addition my lab investigated the genome structure and pathogenesis of Burkholderia cepacia and related species, which are unusual bacteria possessing mutliple chromosomes. These organisms are important for bioremediation of toxic compounds in the environment and are also emerging pathogens, especially in cystic fibrosis patients.

Linda Kenney, Professor, Ph.D.

University of Pennsylvania 1987

Our laboratory is interested in signal transduction and the regulation of gene expression in prokaryotes. In particular, we are studying the two-component regulatory system EnvZ/OmpR that regulates the expression of outer membrane proteins as well as many other genes. OmpR is involved in regulating the expression of virulence genes in many pathogens. Our present work focuses on how OmpR activates genes required for systemic infection (located on Salmonella pathogenicity island 2) in Salmonella enterica.

Amy Kenter, Associate Professor, Ph.D.

Albert Einstein College of Medicine, 1982.

My research program is focused on immunoglobulin (Ig) isotype switching also called switch recombination (SR) which occurs at the Ig heavy chain locus and which is under developmental control. We have detected three DNA-binding proteins which bind to switch regions and which may be involved in the recombination process. We have also identified the presence of double strand breaks located in switch regions which are sequence specific, mitogen inducible and restricted to B lymphocytes.

My laboratory has recently developed a plasmid assay for SR. We are using this switch substrabe to map functional recombination motifs (FRMs) in switch DNA. This information is being used to identify isotype specific switching factors that our studies have revealed.

Howard Lipton, Professor, M.D.

University of Nebraska

Theiler's murine encephalomyelitis virus (TMEV) is an enteric virus and member of the Cardiovirus genus of the family Picornaviridae. Persistent infection of mice with low-neurovirulence TMEV provides a highly relevant experimental animal model for multiple sclerosis (MS). We are interested in elucidating the mechanisms that enable this ordinary lytic virus to cause persistent infection in macrophages recruited into the central nervous system (CNS) of mice. To this end, we are determining TMEV and host cell genes involved in apoptosis of murine macrophages and the role of TMEV carbohydrate co-receptors and protein entry receptor in infection and CNS persistence.

Alan Mclachlan, Professor, Ph.D.

University of Aberdeen (Scotland), 1980.

In my laboratory we study the regulation of HBV gene expression and its relationship to viral replication. In cell culture, we have identified and characterized many of the transcription factors that regulate HBV RNA synthesis and demonstrated a critical role of nuclear hormone receptors in viral tropism. Using HBV transgenic mice, the role of specific liver-enriched transcription factors in modulating HBV transcription and replication in vivo is currently under investigation. The importance of transcriptional regulation in the control of HBV replication in response to various physiological stimuli and metabolic states is also being characterized.

Bellur S. Prabhakar, Professor and Head, Ph.D.

The Johns Hopkins University, Baltimore, 1980

Dr. Prabhakar’ S laboratory is currently pursuing studies that are aimed at understanding the molecular pathogenesis of type-1 diabetes and thyroid autoimmune diseases, and apply lessons learnt from those studies to develop novel therapies to prevent development of and/or suppress ongoing disease. His studies on EAT have shown that GM-CSF can not only completely prevent the development of EAT but can suppress the ongoing disease. Similarly, mice treated with a bi-specific antibody with specificities for CTLA-4 and TSHR could prevent the development of EAT through the induction of antigen specific regulatory T cells that produce IL-10. Further studies are underway to fully delineate the underlying mechanism of GM-CSF action. These studies have been extended to understand the role of regulatory T cells in the NOD animal model of type1 diabetes (IDDM).

As part of his long-standing interest in type-1 diabetes, he recently cloned a novel human gene that is differentially expressed in human insulinomas and can encode four different splice variants. The most fascinating aspect of studies to date is that one of the splice variants (DENN-SV) is over expressed in tumors and cells expressing this variant are resistant to a number of cancer therapies. In contrast, another variant (IG20) is expressed at very low levels or not at all expressed in tumor tissues and renders cells highly susceptible to cancer treatments. Additionally, knockdown studies using SiRNAs have revealed that a 3rd isoform that is constitutively expressed, namely MADD is required for cancer cell survival. Efforts are underway to fully understand the physiological function of these proteins employing transgenic and knockout mice, and to develop novel therapies for cancer.

Lijun Rong, Associate Professor, Ph.D.

Purdue University, 1991.

Research in my laboratory focuses on the molecular mechanisms of enveloped viruses. We are using an integral approach of molecular, cellular, biochemical and structural techniques to identify and dissect essential features of the viral receptors and the viral envelope proteins required for viral/host membrane fusion and viral penetration. Currently we are working with viral glycoproteins of filoviruses, influenza viruses, hepatitis C virus (HCV), SARS-CoV, and Rous sarcoma viruses (RSV). These studies will provide important insights for molecular and cellular understandings of viral infections of these viruses. The information will be used to develop specific entry inhibitors to block viral infection and prevent viral diseases.

Deepak Shukla, Professor, Ph.D.

University of Illinois at Chicago, 1997

The major focus of our research is on understanding the early molecular events associated with viral invasion of human host cells. Using herpes simplex virus (HSV) as a model system we are trying to identify and characterize the viral and cellular components including intra- and inter-cellular signaling pathways that facilitate HSV entry into host cells and spread to uninfected neighboring cells. We are using a multifaceted approach involving genetics, molecular biology, biochemistry and cell biology to achieve our goals. We are also interested in testing our findings in primary human cells and in vivo using a mouse model of the disease. In addition, a significant portion of our research interest is dedicated to developing novel anti-viral agents both as tools for understating the viral invasion mechanisms and future candidates for drug development.

David Ucker, Professor, Ph.D.

University of California, San Francisco, 1981.

Cell death serves a critical physiological process in organismal development, in the shaping of functional cellular networks, and in homeostasis. Our work focuses on the cell autonomous mechanism by which cells effect their own orderly demise, as well as the process by which dead cells assure their non-inflammatory clearance by phagocytic cells. We have examined death-associated events in different apoptotic death responses in a variety of cell types, and we have exploited death-inhibitory gene products to map the order of action of the associated activities.
This work has led to the identification of a thematically conserved cell death pathway. We have defined operationally a point of death commitment by distinguishing necessary and non-lethal [modulatory] steps from those [effector] steps that cannot be dissociated from actual death. Remarkably, we find that the requisite activities of caspases (the family of death-associated cysteine proteases), functioning in a cascade punctuated by Bcl-2, map primarily to the modulatory phase of the process, while cyclin dependent kinase (Cdk) activity, normally associated with cell division and activated in a caspase-dependent manner during cell death, is a critical effector phase constituent. Current efforts seek to identify the critical targets of lethal Cdk action. Our studies of clearance have revealed that the recognition of apoptotic cells is coupled directly to anti-inflammatory responsiveness on the level of transcription, and reflects a profound innate immunity that discriminates live from dead cells without regard to self. We are identifying specific determinants for apoptotic recognition and inflammatory modulation, and delineating the processes within the dying cell that lead to the expression of those determinants. A more complete understanding of the regulation, mechanism, and outcome of the physiological cell death process will offer insights to normal cell and tissue development, and provide new views of aging and treatments for pathological conditions including autoimmune diseases, chronic inflammation, and cancers.

Susan Uprichard, Assistant Professor, Ph.D.

Harvard University, Cambridge MA 1996

The objective of our research is to facilitate the development of effective antiviral therapies and vaccines against Hepatitis C Virus. Although HCV infects more than 2% of the world population and represents a significant public health burden, research efforts to understand HCV infection have been hindered by the lack of experimental systems. For this reason, one initial and continuing focus of the laboratory is the establishment, characterization, and optimization of the experimental in vitro cell culture and in vivo mouse models needed to dissect the HCV life cycle, understand molecular mechanisms of HCV-associated liver disease, and identify the viral-host interactions that determine the outcome of infection. Additionally, projects utilizing our newly established infectious HCV cell culture system include the study of the viral-host interactions that regulate the intracellular trafficking of the virus (e.g. entry, uncoating, assembly, and egress), development of a high throughput screening platform to identify potential HCV inhibitors, genomic screens to identify host cell factors that regulate viral infection, and investigation of RNAi therapeutics for the treatment of chronic HCV infection.

Karl Volz, Associate Professor, Ph.D.

University of California, San Diego, 1981.

In all processes of living cells, form and function are defined by molecular structure and intermolecular recognition. These principles of life are accessible through X-ray crystallography, the only technique for visualizing three-dimensional structures of biological macromolecules at atomic resolution. Using crystallographic approaches, we have analyzed the structural determinants of proteins that regulate "two-component" signal processing systems in bacteria.

William E. Walden, Professor Ph.D.

Washington University, 1983

 

The research focus of my laboratory is on the post-transcriptional regulation of genes of iron transport, storage and utilization, and on the regulation of iron homeostasis in eukaryotes. I am also interested in the mechanisms of translational regulation, specifically translational control via sequence specific RNA binding proteins. A main focus of our work is on the Iron Regulatory Proteins of animal cells.