Department of Microbial Infection and Immunity
Associate Professor in the Department of Microbial Infection and Immunity
College of Medicine
Department of Microbial Infection and Immunity, Center for Microbial Interface Biology, Molecular Virology, Immunology & Medical Genetics, Neuroscience
Biomedical Research Tower 684
460 W. 12th Ave.
Columbus OH 43210
• Multiple sclerosis
• Experimental autoimmune encephalomyelitis
• T cells
Research Lab Goals: The primary goal of my research is to understand the role that T cells play in the onset and progression of multiple sclerosis to understand the cause of disease and develop therapies to treat the disease.
Current Research: Characterizing the T cells that cause damage to the central nervous system in multiple sclerosis. I am focusing on the characterization of the T lymphocytes responsible for damaging the brain and spinal cord in multiple sclerosis. T lymphocytes are a type of white blood cell that helps to destroy cells or tissues that the immune system identifies as foreign. The myelin sheath is recognized as foreign in patients with MS, and therefore T cells specific for attacking myelin are thought to play a large role in disease progression. My research has shown that although all individuals have T lymphocytes specific for attacking myelin, these cells are only active in MS patients. As a result, I have hypothesized that these T lymphocytes are a critical pathological cell in this disease, and that these cells represent an attractive target for future therapeutics. To avoid targeting the essential T lymphocytes needed to fight off natural infections, I have focused on eliminating critical proteins for myelin-specific T lymphocytes. One of these targets is T-bet, which is necessary for the transcription of the myelin-specific T lymphocytes. I have developed a small interfering RNA (siRNA), a molecule that silences the effect of T-bet, and thus diminishes the numbers of myelin-specific T lymphocytes and used it to prevent and treat experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We are also analyzing several novel proteins in pathogenic T cells as potential therapeutic targets for multiple sclerosis.
Determining the role that miRNA play in multiple sclerosis. In our attempts to understand how T cells, which normally protect us from infection, become pathogenic in multiple sclerosis patients, we are analyzing miRNAs which regulate how genes/proteins are expressed in cells. We have found that miRNAs are differentially expressed in the T cells of multiple sclerosis patients, which alters how T cells function in multiple sclerosis patients. Some of these miRNAs promote the development of pathogenic T cells and prevent the development of regulatory cells that should prevent immune responses to self tissues. Thus, miRNA may be a susceptibility factor for the development of multiple sclerosis and may be potential therapeutic targets.
What is the role of vitamin D in protecting the central nervous system from injury during early life? It is well-established that early life events contribute to the onset of multiple sclerosis in young adults. Insufficiency has been an environmental factor that has been associated with susceptibility to multiple sclerosis. We analyze the role of vitamin D in neurons to determine if vitamin D plays a role in protecting the developing central nervous system from injury and, thus, may protect individuals from developing multiple sclerosis. To do this study, we have developed a mouse with an inducible deletion of the vitamin D receptor specifically in neurons so that we can determine if vitamin D in early life compared to adult life enhances susceptibility to central nervous system autoimmunity.
• Primary cell culture
• Flow cytometry
• Western blot
• Experimental autoimmune encephalomyelitis
Co-Investigator, National Institutes of Health, R01, Immune regulation of neuronal injury and repair. January 2013 – December 2017
Principal Investigator, National Multiple Sclerosis Society, Defining the role of miRNA in defective Tregs in multiple sclerosis, October 2014 – September 2017
Co-principal Investigator, Strategic Pharma-Academic Research Consortium, Microbiome marker discovery in multiple sclerosis using metagenomic sequencing technology, January 2015 – December 2016
• PhD: University of Texas Health Science Center, Houston
• Post-doc: National Institutes of Health, Bethesda, MD
• Post-doc: Washington University School of Medicine, St. Louis
• National Multiple Sclerosis Society Research Volunteer Hall of Fame Award, 2015
• Ohio State University Faculty Recognition Award, 2015
• OSU College of Medicine Distinguished Educator Award, 2013
• Harry Weaver Neuroscience Scholar Award, National Multiple Sclerosis Society, 2004-2009
• Lucille P. Markey Special Emphasis Pathway in Human Pathobiology Fellowship, Lucille P. Markey Foundation, Washington University School of Medicine, 1995-1997
• Intramural Research Training Award, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, 1993-1995