Stephen Tomlinson, Ph.D. (Program Director)
Professor & Vice Chair for Research & Faculty Development, Department of Microbiology & Immunology
Dr. Tomlinson studies the biology of the complement system, with a focus on the role of complement in the pathophysiology of inflammation, as well as how inflammation modulates adaptive immunity. Specific areas of interest include immunopathologic mechanisms involved in graft injury following transplantation such as ischemia reperfusion injury, graft immunogenicity and alloresponsiveness. He also has an active neuroimmunology program with a focus on how complement and other components of the innate immune system modulate injury and recovery in stroke, spinal cord injury and, more recently, traumatic brain injury.
Finally, Dr. Tomlinson is investigating how complement activation products modulate anti-tumor immunity via interaction with complement receptors on antigen-presenting cells and T cells. He also has developed a considerable toolbox of complement inhibitors and related reagents that have been utilized to investigate complement-dependent pathogenesis in clinically relevant model systems. Dr. Tomlinson’s research has been the foundation for 25 invention disclosures and 132 patent applications in more than 50 countries, with 53 patents issued.
He has been involved in numerous commercial successes through licensing of drug candidates to the pharmaceutical industry. The genesis of this was through the formation of Taligen Therapeutics Inc. (in collaboration with Drs. Gilkeson and Rohrer and external advisor, Dr. Holers), which was ultimately acquired by Alexion Pharmaceuticals for $111 million upfront with additional trailing milestones that are based on clinical success.
He is currently involved in a new commercialization effort with the formation of AdMIRx, for which intellectual property rights have been secured. Sanderling Ventures has an option to license the technology and has committed funds to patent protection and potentially commercialization. Dr. Tomlinson was the 2014 MUSC Innovator of the Year, and was elected a Fellow of the National Academy of Inventors in 2015.
- Collaborations: Co-authorship with Gilkeson, Rohrer, Atkinson, Li, Liu, Paulos; Grant applications with Atkinson, Gilkeson, Li, Kirkwood, Rohrer, Yu; Additional collaborations with Guo, Paulos.
- Current Postdocs: Zhenxiao Tu, Frank Wang, Xiaofeng Yang, and Chaowen Zheng
Zihai Li, M.D., Ph.D. (Program Co-Director)
Professor & Chair, Department of Microbiology & Immunology
Dr. Li’s research interests are primarily in the field of chaperone biology, immune tolerance and cancer immunology, particularly related to the roles of a key molecular chaperone, gp96, in the endoplasmic reticulum.
His laboratory is the leader in the field of gp96 research by having genetically mapped most of the known key clients of gp96, determined its co-chaperone, pinpointed its client-binding domain, and illuminated its roles in several important biological processes, including immune tolerance, hematopoiesis, innate immunity, oncogenesis and unfolded protein response (UPR). Current interests of the laboratory are inflammation, oncogenesis and cancer immunology with a specific focus on UPR, thrombocyte and regulatory T cells in the processes.
Dr. Li has held 4 investigator-sponsored INDs from the FDA and has been active in translational research through a collaboration with Agenus, a biotech company based on Lexington, MA.
Since Dr. Li’s arrival at MUSC, he has submitted 10 invention disclosures and filed 5 patent applications, with one issued for the treatment of cancer with a combination of conventional drugs and HSP70 vaccine. He is currently evaluating 2 additional technologies for intellectual protection.
His pharma collaborations include safety and feasibility studies with Oncovir, Inc., side effects and dosage studies with Mayo Clinic, and chemotherapeutic comparisons of efficacy and safety with GlaxoSmithKline.
- Collaborations: Co-authorship with Gilkeson, Guo, Liu, Paulos, Rohrer, Tomlinson, Wu, Yang; Grant applications with Atkinson, Bartee, Gilkeson, Guo, Howe, Kirkwood, Liu, Paulos, Tomlinson, Yang; Additional collaborations with Yu.
- Current Postdocs: Alessandra Metelli, Mohammad Salem, Maria Velegraki
Raymond Dubois, M.D., Ph.D.
Professor & Dean of College of Medicine
Dr. Dubois maintains an active research program in 2 areas.
One focus is the study of how chronic inflammation contributes to colorectal cancer initiation, progression and metastasis. He is investigating how the chemokine receptor, CXCR2, modulates infiltration of myeloid-derived suppressor cells (MDSCs) to inflamed colonic mucosa and colitis-associated tumors and how CXCR2-expressing MDSCs contribute to chronic inflammation and tumor growth in the colon via modulation of Th17 cells and colonic CD8+ T cell cytotoxic activity. He also is investigating how a nuclear receptor, PPARd, connects chronic inflammation and tumorigenesis.
A second focus is to understand how PGE2 promotes colorectal cancer formation, progression and metastasis, and how PGE2 promotes tumor growth and progression by induction of tumor epithelial cell proliferation, survival and migration/invasion.
Dr. Dubois has an issued patent on a method to identify and prevent cellular genes needed for viral growth and cellular genes that function as tumor suppressors.
Before joining MUSC, he was on the board of the Arizona Bioindustry Association and Executive Director of the Arizona Biodesign Institute. Dr. Dubois is still in the process of setting up his laboratory at MUSC and, as such, has not yet established MUSC collaborations.
- Current Postdocs:
Carl Atkinson, Ph.D.
Associate Professor, Department of Microbiology & Immunology, & Director, Lee Patterson Allen Transplant Immunobiology Laboratory
Dr. Atkinson is primarily interested in the interplay of the complement system with adaptive immunity in the pathophysiology of inflammation and development of chronic diseases. His major interests include organ transplantation and respiratory diseases. With regard to respiratory disease, an emphasis is on the impact of cigarette smoke exposure on modification of the immune response and disease development in chronic obstructive pulmonary disease. With regard to organ transplantation, a focus is on mechanisms responsible for inflammatory changes that occur in donor organs following brain death, and how this immune priming alters post-transplant inflammation and subsequently modulates alloimmunity and acute and chronic rejection.
Together with the Tomlinson laboratory, his laboratory has established several difficult murine models of transplantation, including lung, liver and vascularized composite allograft (heterotopic and orthotopic) transplantation.
In 2014, Dr. Atkinson co-founded ToleRaM Nanotech, LLC, a company based on technology developed in his laboratory at MUSC for the targeted delivery of immunosuppression therapeutics to organ transplant recipients. ToleRaM Nanotech, LLC has won a number of prestigious awards and recognition, including the 2014 BioProcess International “Emerging Company” Award, keynote abstract at the Techconnect World and National Innovation Summit, acceptance into the South Carolina Launch business development network, and recently a fundable score for an NIH STTR Phase I grant.
Dr. Atkinson has filed 11 invention disclosures, with 35 US and international patent applications, 4 of which have been issued.
- Collaborations: Co-authorship with Gilkeson, Paulos, Rohrer, Tomlinson, Yu; Grant applications with Bartee, Gilkeson, Guo, Kirkwood, Li, Paulos Rohrer, Tomlinson, Yu; Additional collaborations with Wu.
- Current Postdocs: Changhai Li
Eric Bartee, Ph.D.
Assistant Professor, Department of Microbiology & Immunology
My interests as a scientist involve the study of virus-host interactions with particular interest paid to how these interactions can be used to improve therapy for cancer patients, a field known as oncolytic virotherapy. While the oncolytic phenomenon has been observed using a wide variety of viruses, our lab is primarily focused on the therapeutic potential of a virus known as myxoma. In the European rabbit myxoma causes an incredibly lethal disease known as myxomatosis; however, the virus is unable to cause disease in any other known species due to its inability to counteract non-rabbit innate immune responses.
In non-rabbit hosts, this restricts myxoma replication to cells where these responses are either absent or defective, a state which occurs almost exclusively in transformed cancer cells. This naturally occurring cancer tropism allows myxoma to effectively treat a wide variety of cancers including: skin cancer, pancreatic cancer, brain cancer, head and neck cancers, and various cancers of the blood.
Our lab is currently working on three major projects designed to improve the oncolytic potential of the myxoma virus.
- Combining oncolytics and T cell checkpoint inhibitors: Our lab has pioneered a method to deliver T cell checkpoint inhibitors directly to the local tumor microenvironment using novel recombinant myxoma viruses. We are currently exploring: the molecular mechanisms underlying the improved efficacy of these recombinant myxoma constructs, the potential role that the complex tumor microenvironment plays during both oncolytic and checkpoint therapies, and how to further improve outcomes by creating next generation recombinant viruses and combinatorial treatments.
- Oncolytic treatment of multiple myeloma: We are currently exploring whether myxoma virus can be used as a front line therapy to improve treatment of myeloma patients by: directly identifying and eliminating myeloma in vivo, eliminating residual myeloma after chemotherapy, or expelling myeloma from its protected bone marrow niches.
- Improving systemic delivery of myxoma: While myxoma virus is incredibly effective at treating large localized tumors, the virus is often much less efficacious against small metastatic disease.
We are therefore interested in understanding the basic biology of the myxoma virus with special interest paid to the viral proteins which mediate binding of the virus to target cells.
- Current Postdocs:
Gary Gilkeson, M.D.
Professor, Department of Medicine, Division of Rheumatology & Immunology, & Associate Dean for Faculty Affairs & Faculty Development, College of Medicine
Dr. Gilkeson’s research interests focus on the pathogenesis of systemic lupus erythematosus (lupus, SLE), with special emphasis on factors impacting ethnic disparities in outcomes of lupus nephritis. His studies span from basic immunology, inflammation and genetics to population-based studies. He established the SLEIGH (SLE in Gullah Health) study to identify genetic and environmental factors that result in this disparity. He also studies how oxidative stress affects lupus patients and animal models of lupus, the role of the complement system in lupus, and the role of estrogen receptors and genetic factors involved in immunoglobulin class switch recombination.
Dr. Gilkeson has been involved in the development of several new therapies for human immune-mediated diseases. He has active collaborations with 3 biotech/pharma companies related to development of novel therapeutic and diagnostic products. He was directly involved in the startup company Taligen Therapeutics (along with Drs. Tomlinson and Rohrer and external advisor Dr. Holers) that was ultimately acquired by Alexion Pharmaceuticals for $111 million. He has been involved in multiple clinical trials. His research has been the foundation for 8 invention disclosures and 6 patent applications in more than 10 countries, with 6 patents issued. Several patents are licensed.
- Collaborations: Co-authorship with Atkinson, Huang, Li, Rohrer, Tomlinson, Tsao; Grant applications with Atkinson, Li, Liu, Paulos, Rohrer, Tomlinson, Tsao, Wu; Additional collaborations with Yu.
- Current Postdocs:
Philip H. Howe, Ph.D.
Professor & Chair, Department of Biochemistry & Molecular Biology
Dr. Howe is investigating signaling pathways and immune modulation mediated by transforming growth factor (TGFβ1) and Wnt, and cross-talk in models of differentiation and cancer. A current focus is TGFβ1 modulation of B cell development and apoptosis, and how Dab2 serves as a molecular switch to control whether cells undergo apoptosis or autophagy in response to TGFβ. He is investigating how this switch may underlie chemosensitivity and acquired-resistance during tumorigenesis. A further line of investigation is how TGFβ regulation of hnRNP E1 phosphorylation not only regulates translational silencing of select mRNAs involved in EMT/metastasis but also of lncRNAs that may also contribute to tumor progression.
- Collaborations: Grant applications with Li; Additional collaborations with Kirkwood, Paulos, Wu, Yu.
- Current Postdocs: Annamarie Dalton, Simon Grelet, Breege Howley
Yan Huang, M.D., Ph.D.
Professor, Department of Medicine, Division of Endocrinology, Diabetes & Medical Genetics
Dr. Huang’s research interest is the effect of diabetes-associated factors such as dyslipidemia and hyperglycemia on toll-like receptor (TLR) 4-mediated innate immune responses. His laboratory has utilized several animal models for human diabetes and atherosclerosis. Dr. Huang’s laboratory also is investigating the molecular and signaling mechanisms involved in upregulation of pro-inflammatory cytokines such as interleukin 6 by lipopolysaccharide (LPS), high glucose and high saturated fatty acids, and is investigating LPS-triggered TLR4 inflammatory signaling in macrophages. Dr. Huang has 3 invention disclosures in the area of atherosclerosis and diabetes treatment.
- Collaborations: Co-authorship with Gilkeson, Kirkwood, Rohrer; Grant applications with Kirkwood, Rohrer.
- Current Postdocs:
Wei Jiang, M.D.
Clinical and translational immunopathogenesis research in HIV and lupus, B and T cell dysfunction, gut mucosal function, and innate immune activation
- Current Postdocs: Zhenwu Luo, Zejun Zhou
Bei Liu, M.D., MPH
Associate Professor, Department of Microbiology & Immunology
Dr. Liu’s research interests are in the areas of cancer immunotherapy, stem cell-based cancer vaccine and innate immunity. More specifically, her foci are:
- Development of a universal stem cell-based cancer vaccine. The premise is that cancer cells share the expression of molecules (known as “oncofetal antigens”) with embryonic materials and that the immune response against these molecules in the embryonic tissues is cross-protective against cancer. Dr. Liu has identified molecules that are present in both stem cells and cancer cells that can be targets of the immune system, and her research is involved in dissecting the detailed molecular interaction between stem cells and the host immune system.
- Investigating chaperone biology in B cells and plasma cells in both normal and pathological conditions and, in particular, the mechanisms by which the heat shock protein grp94 regulates plasma cells and multiple myeloma.
- The function of dendritic cells and, more specifically, how grp94 modulates dendritic cell function. She is investigating how grp94 and its clients, in particular TLRs and integrins, regulate DC homeostasis, antigen cross-presentation and tumor surveillance against both spontaneous and inflammation-induced cancer.
Dr. Liu has 3 invention disclosures, and 2 patents pending on pluripotent stem cells as cancer vaccines and hsp90 inhibitors for the treatment of cancer and inflammatory diseases. She also is well trained in clinical trial design.
- Collaborations: Collaborations: Co-authorship with Guo, Li, Paulos, Tomlinson, Yang, Yu; Grant applications with Gilkeson, Kirkwood, Li, Yang, Yu; Additional collaborations with Bartee, Rohrer, Wu.
- Current Postdocs: Stephen Iwanowycz
Chrystal Paulos, Ph.D.
Associate Professor, Department of Microbiology & Immunology
Dr. Paulos is a T cell immunologist investigating T cell-based immunotherapies for cancers and autoimmune diseases. Her studies revolve around T cell activation and regulatory mechanisms. With the goal of broadening the utility and efficacy of adoptive cell transfer, her work focuses on improving host preconditioning regimens as well as augmenting various T cell subsets by ex vivo and in vivo manipulation with novel cytokine/chemical cocktails and with co-stimulatory molecules. Her lab also genetically redirects murine and human T cells with novel T cell receptors or chimeric antigen receptors to address their role in aggressive models of cancer (such as pancreatic and ovarian cancer). Dr. Paulos has submitted 3 patents, with 1 issued on the role of targeted drugs or costimulatory molecules in regulating the immune system to reduce autoimmunity or enhance antitumor immunity. Her issued patent has been licensed to Novartis, for whom she acts as a consultant. She is currently involved in a dendritic cell vaccine trial for pancreatic cancer, and also with Dr. Gilkeson in a set of studies integrated with a randomized Phase II trial of mesenchymal stem cell infusion as a potential treatment for refractory lupus.
- Collaborations: Co-authorship with Atkinson, Li, Liu, Rohrer, Tomlinson, Yu; Grant applications with Atkinson, Bartee, Gilkeson, Li, Yu; Additional collaborations with Guo, Howe, Kirkwood, Wu.
- Current Postdocs: Connor Dwyer
Baerbel Rohrer, Ph.D.
Professor & Endowed Chair, Department of Ophthalmology
Dr. Rohrer is studying the role of innate immune effector mechanisms and angiogenesis in age-related macular degeneration, and mechanisms of degeneration and neuroprotection in retinitis pigmentosa. Over the past 10 years, the number of genes associated with photoreceptor dystrophies has almost doubled from ~100 to almost 200 genes. Two key clusters include genes involved in complement activation/neuroinflammation and in energy metabolism, areas of study in Dr. Rohrer’s laboratory. She is utilizing cytotoxicity models of retinal degeneration and different in vivo models to investigate the roles of complement-mediated inflammatory mechanisms, immune changes and the role of antibodies associated with pathogenesis, oxidative stress and angiogenesis (and their interplay) in macular degeneration.
Dr. Rohrer also is a leading innovator at MUSC. She has filed 18 invention disclosures, 23 US and 81 international patent applications, and has 5 US and 51 international patents issued. Her IP contributed to the foundation of 3 startup companies, one of which she co-founded. Additional patents are licensed.
She is on the scientific advisory boards of 2 companies and was previously a consultant for Genentech. Dr. Rohrer also was directly involved with Drs. Tomlinson and Gilkeson and external advisor, Dr. Holers, in the formation of Taligen Therapeutics, which was subsequently acquired by a pharmaceutical company. She has received SBIR funding, was MUSC Innovator of the Year Award in 2013 and elected a Fellow of the National Academy of Inventors in 2014.
- Collaborations: Co-authorship with Atkinson, Gilkeson, Huang, Li, Paulos, Tomlinson; Grant applications with Atkinson, Gilkeson, Huang, Tomlinson; Additional collaborations with Liu.
- Current Postdocs: Masa Ishii, Navjot Shah
Betty Tsao, Ph.D.
Professor of Medicine, Division of Rheumatology & Immunology
Dr. Tsao joined MUSC in December 2015 from UCLA. Her work focuses on identification of genetic risk factors for disease manifestations of systemic lupus erythematosus, a chronic, debilitating autoimmune disease that mainly affects women with features of autoantibody production, immune complex deposition and multiple target organ damage.
Using collected DNA samples and linked clinical and demographic information from thousands of SLE patients and controls, she has contributed to the identification of greater than 80 loci predisposing to SLE. She is now investigating how the underlying risk variants perturb the immune system resulting in systemic autoimmunity and tissue injury.
Dr. Tsao has a strong record of faculty development and mentorship. Dr. Tsao has 1 patent, is collaborating with the biotechnology company Amgen on clinical investigations on lupus through a company funded grant, and has been engaged in clinical trials.
- Collaborations: Co-authorship with Gilkeson; Grant application in process with Gilkeson (she has recently joined MUSC).
- Current Postdocs:
XueZhong Yu, M.D., MS
Professor, Department of Microbiology & Immunology, & Distinguished Endowed Chair, SmartState Cancer Stem Cell Biology Program
Dr. Yu’s research focuses on the biology of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) after allogeneic hematopoietic stem cell transplantation (HSCT). The ultimate goal of these studies is to prevent or treat GVHD while preserving GVL effect, which could greatly enhance the therapeutic potential of HSCT. The major lines of work in Dr. Yu’s laboratory include:
- T-cell differentiation and GVHD development
- Biology of regulatory T cells and their potential application in the control of GVHD
- Understanding how micro-RNAs regulate T and B cell responses after allogeneic HSCT
- Evaluation of metabolic pathways or intermediates as biomarkers and therapeutic targets in GVHD and leukemia relapse.
Dr. Yu has collaborated with companies such as Novartis, Rigel and CTI BioPharma in evaluating new drugs in translational studies. He has 1 invention disclosure and is in the process of filing a patent with Dr. Tomlinson and searching for a commercial partner to develop a complement inhibitor to treat GVHD.
- Collaborations: Co-authorship with Atkinson, Bartee, Liu, Paulos, Tomlinson, Wu; Grant applications with Atkinson, Bartee, Paulos, Guo, Liu, Paulos, Tomlinson, Wu; Additional collaborations with Gilkeson, Howe, Li, Yang.
- Current Postdocs: Anusara Daenthanasanmak, Hung Nguyen, Yongxia Wu