T32 Eligible Mentors

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: Frank Wang, Xiaofeng Yang, and Chaowen Zheng

Bibliography

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. 

Bibliography

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:

Bibliography

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

Bibliography

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.

Bibliography

Wei Jiang, M.D.

Associate Professor, Department of Microbiology and Immunology

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

Bibliography

Meenal Mehrotra, MD, PhD

Assistant Professor, Department of Pathology and Laboratory Medicine

Dr. Mehrotra’s research interests focus on a debilitating pediatric bone disease, Osteogenesis imperfecta (OI), which is the most common hereditary bone disease, characterized by reduction in quality of bone matrix that leads to repeated fractures and bone deformity. Immune cells such as T cells have been shown to play an important role in bone formation and turnover rates. However, whether T cells play a role in OI, a disease with high turnover and high fracture rates, has never been investigated before. Dr. Mehrotra’s lab is focused on characterizing the T cells specifically T regulatory cells (Tregs) in mice models of OI and their cross talk with the osteoblasts and osteoclasts. An understanding of the contribution of Tregs to bone healing in OI could help to develop new avenues of therapy for OI through the use of Tregs and its factors, thereby providing potential new translational approaches in the treatment of OI.

Another project in the Mehrotra lab focusses on the primary bone cancer, osteosarcoma. The objective of the proposal is to identify SphK1/S1P/S1PR1 axis as the main mechanism regulating the cross talk between non-malignant osteoblasts and osteosarcoma cells, in the microenvironment, which causes the progression of osteosarcoma. These studies are significant and innovative as they establish a unique role of osteoblasts in osteosarcoma microenvironment, which can be targeted to suppress its progression through lipid metabolism and signaling. These findings, thus, have the potential to be translated to the clinics by developing potential anti-tumor therapies.

  • Collaborations: Dr. Shikhar Mehrotra, Dr. Besim Ogretmen.
  • Current Postdocs: In-Hong Kang

Bibliography

Sophie Paczesny, MD, PhD

Professor & Chair, Department of Microbiology and Immunology and Pediatrics & Co-Leader, Cancer Immunology Program

Dr. Paczesny is Professor and the Chair of the Department of Microbiology and Immunology and is the Hollings Cancer Center Cancer Immunology Program co-leader. Her laboratory is nationally, as well as internationally, recognized for its expertise and achievements in the Hematopoietic Stem Cell Transplantation field of biomedical research. She has pioneered the study of biomarkers for complications post allogeneic stem cell transplantation and is now transitioning the laboratory work into clinical practice. She has extensive expertise in proteomics/biomarkers, T lymphocyte biology and mechanisms of immunity and tolerance as well as translating novel drug-targetable biomarkers to treatment. She has also a long track-record of mentoring and has supervised more than 50 postdoctoral fellows, clinical fellows, medical students, PhD students, and undergrad students. She is currently funded by 1 NIH U01 grant, 2 NIH R01 grant, 1 NIH R21 grant, and 1 NIH U54 grant. She has published 113 scientific manuscripts in top tier medical journals. She has collaborated with several industry partners as well as many collaborators at other large institutions.

  • Current Postdocs: John Jiang, Jaden Fu

Bibliography

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

Bibliography

Jessica Thaxton, Ph.D.

Assistant Professor, Department of Orthopaedics and Physical Medicine

The long-term goal of the Thaxton lab is to create and implement novel immune-based strategies that advance care for sarcoma, head and neck, and metastatic bone disease cancer patients.  As an academic lab it is essential to undertake research that is basic in nature yet has direct clinical implication. For this reason the Thaxton lab works with clinicians to determine important clinical problems and design research to address the basic science mechanisms that may enable better clinical care.

Research in the Thaxton lab is focused on overcoming the cell stress response induced by solid tumors in immune cells. The lab has discovered that the cell stress response, orchestrated by endoplasmic reticulum stress sensors (ER), determines immune cell fate decisions through programming activation, metabolism, protein synthesis, and cell death. The ER contains multiple unique and unexplored therapeutic targets to repair dysregulation programs in immune cells in tumor to invigorate responses to immunotherapy to benefit cancer patients.

Dr. Thaxton has collaborated with companies such as GlaxoSmithKline and TEVA Pharmaceuticals to test new combinatorial strategies for cancer immunotherapy. She has a filed patent surrounding ER stress targets in cancer immunotherapy and aims to establish a small business to develop novel therapeutics.

Bibliography

Betty Tsao, Ph.D.

Professor, Department 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).

Bibliography

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.

Bibliography