Department of Microbiology and Immunology

About Us

James S. Norris, Ph.D.

Professor and Chairman,
Department of Microbiology and Immunology

Dr. Norris received his Ph.D. in Biology from the University of Colorado, Boulder, in 197l. He did postdoctoral work as an NIH and ACS Fellow under the mentorship of Dr. Jack Gorski at the University of Illinois in the Department of Physiology-Biophysics and Peter Kohler, in the Reproductive Research Branch, NICHD. In 1973, he began his academia career as Instructor, in the Department of Cell Biology, Baylor College of Medicine.  In 1977 he moved to the Departments of Medicine and Physiology/Biophysics, at the University of Arkansas for Medical Sciences where he rose through the ranks to Associate Professor.  Dr. Norris moved to the Medical University of South Carolina in 1988 as Professor of Medicine and Biochemistry and Molecular Biology.  In 1996 he became Vice Chairman of the Department of Microbiology/Immunology and in 2000 Chairman.  He has been on the editorial boards for the International Hormonal Carcinogenesis Symposium 1991-93; Cellular Pharmacology (Editorial Board) 1996-98; Gene Therapy & Molecular Biology (Editorial Board) 1997 – present; Journal of Pharmacology and Experimental Therapeutics (Editorial Advisory Board) 2001-present.  Since 1998, he has been on the International Society of Cancer Gene Therapy Council, President of the International Society of Cancer Gene Therapy (2005-2006); Councilor for the American Society of Microbiology Chairs (2006-2008), and currently, belongs t AAAS; American Society of Cell Biology; British Association for Cancer Research; American Society for Microbiology; American Association for Cancer Research; British Society for Gene Therapy; Society for Basic Urological Research; American Society of Gene Therapy; International Society for Cancer Gene Therapy; American Urological Association (associate) and American Chemical Society.  He has served on numerous NIH/DOD/NCI review panels.  His research efforts are focused on gene therapy treatment of prostate, bladder, kidney, and head and neck cancer in combination with small molecule inhibitors of sphingolipid metabolism. Dr. Norris is one of the founders of a small biotech company, SphingoGene, Inc.

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Carl Atkinson, Ph.D.

Assistant Professor

Heart transplantation is an accept treatment modality for patients with end-stage heart disease. These patients have reached the end of conventional pharmacological therapy or surgical interventions and the only therapeutic option left is heart transplantation. Current first year survival rates post transplantation varies between 80-95%, and patients surviving beyond the first can expect an average half-life of 11 years. While these results are acceptable patients eventually succumb to chronic rejection which manifests as an obliterative vascular lesion which restricts the hearts blood supply and eventually leads to heart failure. The precise mechanisms that contribute to the development of chronic rejection are unknown, but recent data implicates the early ischemic damage these hearts receive due to the transplant process and brain death.

Results from kidney transplantation have shown that the quality of the donor organ is important for post transplant survival. Organs donated from living donors perform better than those harvested from cadaveric donors. It is believed that the processes stimulated during brain death in these cadaveric donors, activates the donor heart rendering it more susceptible to ischemic damage, upon implantation, and ultimately acute and chronic rejection. The mechanisms responsible for these inflammatory changes to the donor organ are poorly characterized. Our research focuses on the elucidation of these mechanisms and the application of novel therapies that can be applied to the donor prior to transplantation to limit donor organ damage. During brain death all of the organs in the body are exposed to ischemia and chaotic changes in blood supply and pressure. Our studies have implicated the complement system in the activation of the donor heart. The complement system is composed of a series of serum proteins that work in a concerted fashion to induce cell death, promote inflammation and pro-inflammatory cytokines. We have been working with complement inhibitory proteins with the aim to reduce complement mediated brain death induced inflammation and ultimately to reduce the incidence and severity of both acute and chronic rejection. 

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Edward Balish, Ph.D.

Professor Emeritus

Medical mycology, immunity to Candida albicans, immunotherapy of candidiasis, gnotobiology, transgenic mice, knockout mice, inflammatory bowel disease.

Recent Publications:
Schofield DA, Westwater C, and Balish E. 2005. Divergent chemokine, cytokine and beta-defensin responses to gastric candidiasis in immunocompetent C57BL/6 and BALB/c mice. J Med Microbiol 54(1):87-92.

Schofield DA, Westwater C, Warner T, and Balish E. 2005. Differential Candida albicans lipase gene expression during alimentary tract colonization and infection. FEMS Microbiol Lett 244(2): 359-365.

Balish E, Warner TF, Nicholas PJ, Paulling EE, Westwater C, and Schofield DA. 2005. Susceptibility of germfree phagocyte oxidase- and nitric oxide synthase 2-deficient mice, defective in the production of reactive metabolites of both oxygen and nitrogen, to mucosal and systemic candidiasis of endogenous origin. Infect Immun 73(3): 1313-1320.

Westwater C, Balish E, and Schofield DA. 2005. Candida albicans-conditioned medium protects yeast cells from oxidative stress: a possible link between quorum sensing and oxidative stress resistance. Eukaryot Cell 4(10): 1654-1661.

Westwater, C., Balish, E., Warner, TF., Nicholas, PJ., Paulling, EE. and Schofield, DA. 2007. Susceptibility of gnotobiotic transgenic mice (Tgε26) with combined deficiencies in natural killer cells and T cells to wild-type and hyphal signaling-defective mutants of Candida albicans. Journal of Medical Microbiology 56(9):1138-44.

Westwater, C., Schofield, DA., Nicholas, PJ., Paulling, EE. and Balish, E. 2007. Candida glabrata and Candida albicans; dissimilar tissue tropism and infectivity in a gnotobiotic model of mucosal candidiasis. FEMS Immunology and Medical Microbiology 51(1):134-139.

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Azizul Haque, Ph.D.

Assistant Professor

Dr. Haque's laboratory conducts research in the areas of tumor immunology, transplantation immunology and autoimmunity. In tumor immunology, we are investigating the mechanisms by which malignant tumors such as lymphoma, prostate and melanoma evade immune recognition via MHC class I and II pathways. Lymphoid malignancies such as B-cell lymphomas arise at distinct stages of cellular development and maturation, potentially influencing immune recognition and the functional interaction of these cells with other components of the immune system. Burkitt lymphoma (BL) is a highly malignant B-cell tumor characterized by chromosomal translocation that constitutively activates the c-myc oncogene. Epstein-Barr virus (EBV) transforms primary B-cells in vitro, and results in the establishment of lymphoblastoid cell lines (B-LCL). While B-LCL efficiently process and present antigens to T cells in the context of both MHC class I and class II molecules, BL cells have been shown to be deficient in their ability to process and present antigens by both pathways, and the mechanisms remain unknown. Studies in Dr. Haque's laboratory are probing the factors responsible for defective antigen processing and immune recognition in the context of MHC class II molecules. While MHC class I-restricted CD8+ T cells are effector cells in anti-tumor immune responses, MHC class II-restricted CD4+ T cells can also destroy tumors by direct killing. CD4+ T cells can also play critical roles in initiating, regulating, and maintaining anti-tumor immune responses. Because most B-cell tumors express MHC class II molecules, these tumors can be potential target for CD4+ T cells. Elucidating the mechanisms of loss of immune recognition in the context of MHC class II molecules will contribute to the development of effective immunotherapeutics against B-cell lymphomas.

In transplantation immunology, we are investigating the regulation of immune responses in lung allograft rejection using a rat model of lung transplantation. In collaboration with Dr. Wilkes (Indiana University), we have found that the immune responses during lung allograft rejection may be directed against certain connective tissue proteins such as type V collagen. Ongoing studies in the laboratory are actively investigating the implications of collagen V-reactive T cells in the immunopathogenesis of chronic lung allograft rejection. Dr. Haque's laboratory is also investigating the role of small molecules in the suppression of autoimmune diseases.

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Songqing He, M.D.; Ph.D.

Research Assistant Professor

My primary area of research is liver regeneration and mechanisms of liver ischemia-reperfusion injury after liver surgery, including liver transplantation. The use of small-for-size liver graft, for transplantation could greatly increase the donor pool, but such transplants are associated with high failure rates. Suppression of liver regeneration is a key mechanism responsible for such transplant failure. The complement system plays an important role in regeneration, but may also cause direct injury to the liver after transplantation.

We propose to investigate complement-dependent mechanisms in impairment of liver regeneration and ischemia reperfusion injury. We have developed mouse models to study complement effector mechanisms responsible for liver regeneration or its inhibition after small size liver transplants, partial hepatectomy, as well as for liver damage caused by ischemia reperfusion.

We also plan to examine whether specifically targeted complement inhibitors serve as potential therapeutic targets to restore liver regeneration and alleviate ischemia reperfusion injury. These studies are anticipated to identify optimum points in the complement activation pathway for pharmacological intervention.

Dr. He received his Ph.D. from Hepatic Surgery Center Affiliated Tongji Hospital Tongji Medical College Huazhong University of Science and Technology, P. R. of China.

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Christina (Voelkel-)Johnson, M.S. Ph.D.

Assistant Professor

Tissue homeostasis is a balance between life (cell growth) and death (apoptosis). When this balance is lost, uncontrolled cell growth leads to cancer and threatens the organism. In my laboratory we seek to understand the apoptotic process and to use this knowledge to develop novel treatment strategies against cancer.

Modulation of anti-apoptotic proteins
Current research is focused on a protein called TRAIL (tumor necrosis factor-related apoptosis inducing ligand). TRAIL induces apoptosis via death receptors on the cell surface. Initial studies suggested that TRAIL selectively induces apoptosis in malignant cells. However, more recently it has been shown that many cancer cells actively resist TRAIL-mediated apoptosis. We found that resistance to soluble TRAIL can be overcome by combination with the chemotherapeutic agent doxorubicin, which decreases the expression of short half-life proteins such as cFLIPS, XIAP, and survivin via production of reactive oxygen species that result in phosphorylation of EF-2 (inhibition of translation).  This project is supported by NIH/NCI.
White et al. Free Radicals in Biology and Medicine (in press)
White et al. Cancer Biol Ther. 2006 Dec;5(12):1618-23.
Kelly et al. Cancer Biol Ther. 2002 Sep-Oct;1(5):520-7.
Voelkel-Johnson et al. Cancer Gene Ther. 2002 Feb;9(2):164-72.
Therapeutic applications
Infection of cells with an adenovirus that expresses full-length membrane bound TRAIL (AdTRAIL) can also induce apoptosis. Adenoviral infection depends on expression of CAR, which is frequently downregulated in cancer. A novel class of chemotherapeutic agents called histone deacetylase inhibitors (HDACi) can restore CAR expression. We have recently shown that HDACi selectively enhance surface CAR in malignant LNCaP but not normal prostate epithelial cells. As a result HDACi pre-treatment selectively enhanced  AdTRAIL-induced apoptosis. Current translational studies include the treatment of prostate cancer with combination therapy and treatment of bladder cancer using intravesical gene therapy. This project is supported by NIH/NCI.
Kasman L, Lu P, Voelkel-Johnson C. Cancer Gene Ther. 2007 Mar;14(3):327-34.
El-Zawahry et al. Cancer Gene Ther. 2006 Mar;13(3):281-9.
Sphingolipids in apoptosis
In addition, we are investigating the role of ceramide in TRAIL-mediated apoptosis. Ceramide is a metabolite of sphingolipid metabolism that is involved in numerous physiological responses, including apoptosis. In the colon, ceramide levels are reduced in malignant tissue compared to the normal mucosa. Treatment with ceramidase inhibitors, which should restore ceramide levels, can prevent or eliminate liver metastases in a mouse model. Ceramide has also been shown to overcome resistance to FasL, a death ligand similar to TRAIL. We believe that defective ceramide signaling may be responsible for resistance to TRAIL. Recent research has focused on the ceramide synthase LASS6/CerS6. This project is supported by the Center for Colon Cancer Research at the University of South Carolina (http://cccr.sc.edu/).
Voelkel-Johnson et al., Mol Cancer Ther. 2005 Sep;4(9):1320-7.

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In Press Article: Abstract and Figures from Oxidative stress sensitizes bladder cancer cells to TRAIL-mediated apoptosis by downregulating anti-apoptotic proteins: 

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Laura Kasman, Ph.D.

Assistant Professor

Graduate Studies Coordinator for Microbiology and Immonology

I am interested in virus-host interactions.  Currently my research focuses on maximizing virus-host interactions for use in immunotherapy of bladder cancer.
Anti-tumor immune responses are by necessity autoimmune responses.  It has been recently recognized that a characteristic of tissue-specific autoimmune diseases is the formation of ectopic germinal centers, or new tiny lymph nodes, within the tissue itself. For example, germinal center-like lymphoid tissues are found in joints affected by rheumatoid arthritis.  These germinal centers have been shown to be highly specific for self antigens.  If the process of lymphoid neogenesis could be replicated in tumor tissue, the resulting anti-tumor response may be more effective than current methods.
The organization of ectopic germinal centers appears to be dependent on the presence of several specific cytokines.  This project, in collaboration with Dr. Christina Johnson, involves optimization of conditions for using adenoviral vectors to deliver the genes for these cytokines to bladder tumors.  We have shown that some histone deacetylase inhibitors increase both adenoviral infection and transgene expression in bladder cancer cells in vitro.  The next step is showing effectiveness in a mouse model of bladder cancer.  Ultimately, the goal is to stimulate a long-lasting anti-tumor immune response capable of preventing the recurrences that occur in more than 50% of bladder cancer cases.

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Xiang Liu, M.D., Ph.D.

Assistant Professor

My work is focused on optimization gene delivery vectors that deliver programmed cell death inducing genes (FasL or Apoptin) to kill cancer cells (prostate and head and neck origin). The ultimate goal of my research is to develop delivery systems that specifically destroy tumor cells while leaving normal cells intact. In addition, I also use combining gene therapy with small molecule-based therapeutics, which target to ceramide metabolism pathway, to enhance cytotoxicity response or sensitize cells to the current therapies. To date these studies have determined novel mechanisms by which prostate cancer cells or head and neck cells develop resistant to induction of apoptosis and thus to most current standard treatments in clinical medicine.  The new compounds develop show promise in overcoming this type of resistance and will be tested in the clinic in the future.

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Harold May, Ph.D.

Professor

Environmental microbiology focuses on the role of microorganisms in the synthesis and degradation of natural and anthropogenic compounds, and on the interactions of microbes with the physical environment and other organisms. The microbial cycling of chemicals, toxic and otherwise, is crucial for the stability of healthy ecosystems. Research in my laboratory includes studies on the physiology, ecology and biochemistry of microorganisms engaged in various forms of anaerobic metabolism including exploratory work with electrode reducing bacteria. An incoming graduate student could pursue any one of several ongoing projects. These include investigations on the reductive dechlorination of polychlorinated biphenyls (PCBs), chlorobenzenes and chlorinated ethenes, the anaerobic oxidation of chlorinated solvents, and the biodegradation of petroleum when concurrent with halogenated organic compounds. Other projects are focused on the halogenation and dehalogenation of chlorinated hydroquinone metabolites produced by basidiomycete fungi as part of a natural biogeochemical chlorine cycle. All of the above research includes chemical analysis of degradation products, isolation and characterization of microorganisms, biochemical analysis and the molecular monitoring of bacterial communities (e.g. by restriction fragment length, sequencing or denaturing gradient gel electrophoresis analysis of amplified 16S rDNA). A proteomic and enzymological approach is planned for the study of dehalogenases. In addition to collaboration with other MUSC faculty, we are working with researchers from the University of Maryland Biotechnology Institute (Center of Marine Biotechnology), the Woods Hole Oceanographic Institute, and SINTEF of Norway. These collaborations offer the student extended educational opportunities. Students are welcome to join my laboratory and pursue any of these challenging areas of research.

Environmental microbiology focuses on the role of microorganisms in the synthesis and degradation of natural and anthropogenic compounds, and on the interactions of microbes with the physical environment and other organisms. The microbial cycling of chemicals, toxic and otherwise, is crucial for the stability of healthy ecosystems. Research in my laboratory includes studies on the physiology, ecology and biochemistry of microorganisms engaged in various forms of anaerobic metabolism including exploratory work with electrode reducing bacteria. An incoming graduate student could pursue any one of several ongoing projects. These include investigations on the reductive dechlorination of polychlorinated biphenyls (PCBs), chlorobenzenes and chlorinated ethenes, the anaerobic oxidation of chlorinated solvents, and the biodegradation of petroleum when concurrent with halogenated organic compounds. Other projects are focused on the halogenation and dehalogenation of chlorinated hydroquinone metabolites produced by basidiomycete fungi as part of a natural biogeochemical chlorine cycle. All of the above research includes chemical analysis of degradation products, isolation and characterization of microorganisms, biochemical analysis and the molecular monitoring of bacterial communities (e.g. by restriction fragment length, sequencing or denaturing gradient gel electrophoresis analysis of amplified 16S rDNA). A proteomic and enzymological approach is planned for the study of dehalogenases. In addition to collaboration with other MUSC faculty, we are working with researchers from the University of Maryland Biotechnology Institute (Center of Marine Biotechnology), the Woods Hole Oceanographic Institute, and SINTEF of Norway. These collaborations offer the student extended educational opportunities. Students are welcome to join my laboratory and pursue any of these challenging areas of research.

Environmental microbiology focuses on the role of microorganisms in the synthesis and degradation of natural and anthropogenic compounds, and on the interactions of microbes with the physical environment and other organisms. The microbial cycling of chemicals, toxic and otherwise, is crucial for the stability of healthy ecosystems. Research in my laboratory includes studies on the physiology, ecology and biochemistry of microorganisms engaged in various forms of anaerobic metabolism including exploratory work with electrode reducing bacteria. An incoming graduate student could pursue any one of several ongoing projects. These include investigations on the reductive dechlorination of polychlorinated biphenyls (PCBs), chlorobenzenes and chlorinated ethenes, the anaerobic oxidation of chlorinated solvents, and the biodegradation of petroleum when concurrent with halogenated organic compounds. Other projects are focused on the halogenation and dehalogenation of chlorinated hydroquinone metabolites produced by basidiomycete fungi as part of a natural biogeochemical chlorine cycle. All of the above research includes chemical analysis of degradation products, isolation and characterization of microorganisms, biochemical analysis and the molecular monitoring of bacterial communities (e.g. by restriction fragment length, sequencing or denaturing gradient gel electrophoresis analysis of amplified 16S rDNA). A proteomic and enzymological approach is planned for the study of dehalogenases. In addition to collaboration with other MUSC faculty, we are working with researchers from the University of Maryland Biotechnology Institute (Center of Marine Biotechnology), the Woods Hole Oceanographic Institute, and SINTEF of Norway. These collaborations offer the student extended educational opportunities. Students are welcome to join my laboratory and pursue any of these challenging areas of research. Dr. May is also an acting partner in MFC Technologies LLC.

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Janardan Pandey, Ph.D.

Professor

The primary focus of my laboratory is directed towards understanding the mechanisms underlying the involvement of immunoglobulin allotypes in spontaneous and treatment-induced clearance of infection with hepatitis C virus.  Genetics of immunity to malaria is also being investigated.  We have recently added the genetic control of humoral immunity to the tumor-associated antigen MUC1 to our investigations. These studies are supported in part by grants and contracts from the National Institutes of Health and the Centers for Disease Control and Prevention.

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Semyon Rubinchik, Ph.D.

Research Assistant Professor

I received my PhD in Molecular Biology at the University of Toronto. My post-graduate work involved the development of adenoviral and adeno-associated virus vector for gene therapy of genetic diseases and cancer.

Currently, I am interested in the interactions between exogenous and endogenous viruses that may play a role in head and neck carcinogenesis. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) are exogenous tumor viruses associated with 20 to 30% of oropharyngeal squamous cell carcinomas (OSCC), and virtually all undifferentiated nasopharyngeal carcinomas (NPC), respectively. We discovered that both HPV and EBV transactivate a superantigen encoded within the envelope gene of human endogenous retrovirus HERV-K18 on chromosome 1. Superantigens are viral or bacterial proteins that elicit strong T-cell activation and cytokine production. NPC are often associated with extensive T-cell infiltrates that promote rather than inhibit tumor growth, while little is known about the T-cell response to HPV+ OSCC.  We postulate that the HERV-K18 superantigen contributes to T-cell pathology in the tumor microenvironment, and consequently, to tumor progression in NPC and HPV+ OSCC. We are developing in vitro and in vivo models to evaluate the impact of superantigen activated T-cells on carcinogenesis. Accordingly, we have set up an in vitro system for immortalizing primary human tonsil (oropharyngeal) and adenoid (nasopharyngeal) epithelial cells, and are developing potential therapeutic agents to control HERV-K18 activated T-cells.

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Michael Schmidt, Ph.D.

Professor and Vice Chairman of
Microbiology and Immunology
Director, Office of Special Programs

The current focus of my laboratory is the delineation of the complex dynamic interplay between microbial biofilms and their human host. This project presently focuses on the microbial contributions to carcinogenesis of the human colon and is in the process of acquiring the foundation knowledge that will enable the development of a molecular test that will allow the direct examination of the significance of an individual's normal intestinal flora in the development of colon cancer. The lab has begun to expand the focus of this work by studying the complex dynamic between oral microbes and the host in order to ascertain if the work pioneered in the lower GI track by the lab can facilitate the development of a rapid diagnostic that would forecast the likelihood of developing oral cancer and/or cardiovascular disease.
There are three specific focus areas that lab is currently working towards in order to achieve a goal of an understanding of the role that the endogenous microflora play in the onset diseases processes such as cancer, periodontitis and cardiovascular disease. The first is concentrating its efforts on developing PCR primers for the characterization of complex, uncharacterized, microbial communities using molecular markers other than 16S rRNA. To that end the lab is presently characterizing a series of PCR primer sets against those microorganisms and their respective gene products implicated in the triggering of colon cancer along with those microbes and their respective gene products implicated in limiting and/or preventing this devastating disease. The oral cavity of humans is as equally complex as that of the lower GI track. There are strong clinical indicators implicating the endogenous microflora of humans as triggers of cardiovascular disease. The lab has begun to use the same approach taken in the developing an understanding of the role of the indigenous microflora in triggering colon cancer in developing molecular tests for the determining the role of indigenous microflora in triggering periodontal disease that in turn may trigger cardiovascular disease.

The second focus area is working towards the clinical translation of the fundamental basic science developed in pursuing the question above. Major efforts in the lab have recently been using multiplex PCR measurements against genomic samples of the microflora associated with human stool specimens isolated from three distinct patient populations; healthy subjects, patients with polyps and patients with a diagnosis of colon cancer. Optimal primer sets are being used in order to ascertain the population distribution of bacteria implicated in the carcinogenic/mutageneic transformation of endogenous substances produced by the host (bile acids transformed into co-mutagenic substances) and the relative population distribution of the microbial flora thought to confer protection to the colonic environment. Given the complexity of the data associated with the first two tasks before the lab, the third area we are investigating is the utility of employing an artificial neural network in order to model the data in concert with clinical parameters collected from patients in order to refine the focus of the variables required from the molecular tests. Taken together the combined efforts from each of the focus areas should enable us to initially to identify the clinical indicators necessary for the prediction of individual's likelihood of a susceptibility towards colon cancer and ultimately, lead us to a better understanding of the role of the indigenous microflora of the host in triggering chronic disease processes.

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Natalie Sutkowski, Ph.D.

Assistant Professor

Superantigens are microbial proteins that over-stimulate the immune system.  Recently, we discovered that a superantigen sleeps within our genes, encoded by a human endogenous retrovirus, named HERV-K18.  The human genome project revealed that roughly 8 % of our genome derives from viral origin, much of it composed of Human Endogenous Retrovirus (HERV) sequences.  HERVs are evolutionary remnants, originating from retroviral infection of germ cells over many thousands of years.  The vast majority of HERVs are defective and incapable of virus replication, but many HERVs encode functional genes, like the HERV-K18 superantigen.  This superantigen can be awakened by infection with the common herpesvirus, Epstein-Barr virus (EBV), and also by interferon-α, which is produced in response to virus infection.  The "awakening" causes a localized immune response with T cell activation and cytokine production at the site of EBV infection.  HERV-K18 activation might therefore affect EBV related diseases, because superantigens cause inappropriate immune responses.

More than 90% of adults are latently infected throughout their entire lives with EBV.  The infection is generally benign, but occasionally EBV causes cancer.  EBV infects both B cells and epithelial cells.  When it turns cancerous, it can cause different B cell lymphomas, including Burkitt's, Hodgkin's, AIDS related lymphomas, and post-transplant lymphoproliferative disease, as well as epithelial cancers like nasopharyngeal carcinoma.  EBV has also been implicated in the etiology of autoimmune diseases, like rheumatoid arthritis, multiple sclerosis, lupus, and diabetes.  It is unclear why certain individuals are more susceptible to EBV related disease.  We propose that the inappropriate immune stimulation elicited by the HERV-K18 superantigen as a result of EBV infection, contributes to EBV pathology in susceptible individuals.  This theory is currently being tested in our lab with in vitro models and humanized mouse models of disease.  Efforts are aimed at controlling the superantigen stimulation through immunotherapy and gene therapy, ultimately, to prevent EBV lymphoma and nasopharyngeal carcinoma.  Recent work in our lab suggests that other tumor viruses also elicit the HERV-K18 superantigen, and thus controlling its expression might have far reaching therapeutic benefit. 

In summary, our scientific focus is to study the interactions of viruses with the immune system, with a translational emphasis on cancer.  There are three major projects ongoing, each involving manipulation of tumor virus immunity: 1) in lymphomagenesis, 2) in carcinogenesis, and 3) for human monoclonal antibody production. In addition, we are actively searching for other HERV superantigens. Since HERV sequences make up so much of the human genome, it is likely that there are other HERV superantigens that influence our immune system. We welcome students and postdocs interested in immunology and virus research. 

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Stephen Tomlinson, Ph.D.

Professor

Research activities are focused on the biology of the complement system. Complement is a group of over 30 soluble and cell surface proteins that represent a crucial component of immune system. The laboratory is involved in the following areas of study:

1. INFLAMMATION: We are using genetically modified mice and complement inhibitory strategies to investigate the role of complement in various autoimmune and inflammatory diseases and in disease states associated with organ transplantation. A particular interest is the development of novel complement inhibitors that can be specifically targeted to sites of complement activation and disease. A targeting approach for complement inhibition has the potential to alter the inflammatory profile relative to systemic inhibition, and can enhance efficacy without causing immunosuppression.
2.  CANCER: Complement plays an important role in both the induction and effector phases of a humoral immune response to cancer. Immunity may be naturally induced or may be the result of passive or active immunotherapies. We are studying the role of complement in tumor immunity and investigating strategies to enhance a normally ineffective humoral immune response to tumor cells. We are particularly interested in improving the outcome of vaccination strategies and of monoclonal antibody-mediated therapy of cancer.
Some representative publications:
Atkinson, C., Lu, B., Qiao, F., Burns, T., Tsokos, G and Tomlinson, S. (2005) Targeted complement inhibition by C3d recognition ameliorates tissue injury without increasing risk of infection. J. Clin. Invest., 115, 2444-2452.
Imai, M., Landen, C., Ohta, R., Cheung, N.K.V. and Tomlinson, S. (2005) Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of a murine metastatic cancer. Cancer Res. 65, 10562-8.
Qiao,F., Atkinson, C., Song, H., Pannu, R, Singh, I. and Tomlinson, S. (2006) Complement plays an important role in spinal cord injury and represents a therapeutic target for improving recovery following trauma. Am. J. Pathol. 169, 1039-1047.
Huang, Y., Qiao, F., Abagyan, R., Hazard, S. and Tomlinson, S. (2006) Defining the CD59-C9 binding interaction. J. Biol. Chem. 281:27398-27404.
Atkinson, C., Zhou, H.,  Qiao, F,. Varela, J., Yu, J, Song, H,. Kindy, M., Tomlinson, S. (2006) Complement dependent P-selectin expression and injury following ischemic stroke. J. Immunol. 177:7266-74

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Gabriel Virella, M.D., Ph.D.

Professor of Microbiology and Immunology
Vice Chairman of Education

Dr. Virella’s research is focused on the investigation of the role of autoimmune and inflammatory processes in the pathogenesis of human atherosclerosis. His lab has established unique protocols for the isolation and characterization of human antibodies to modified lipoproteins, the definition of lipoprotein modification involved in autoimmune reactions, and the biological properties of antigen-antibody complexes prepared with human modified LDL and human purified antibodies to modified LDL. The sum of the data generated in collaboration with Dr. Maria Lopes-Virella supports a pathogenic role for the autoimmune response to modified lipoproteins. Currently we are investigating parameters that may have a modulatory effect on the consequences of autoantibody formation against modified LDL, such as the ration of IgG vs. IgM antibodies and on the definition of immune complex-mediated pathogenic mechanisms responsible for the development of diabetic nephropathy.

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