Dr. Harding graduated magna cum laude and with Highest Honors in Biology from Harvard College in 1979. He completed his M.D. and Ph.D. in Cell Biology at Washington University of St. Louis in 1985. He served as Resident in Pathology, Chief Resident in Pathology, Instructor in Pathology and Assistant Professor of Pathology at Washington University. Since 1993 he has been a faculty member at CWRU/University Hospitals Case Medical Center. He is currently the Joseph R. Kahn Professor and Chair of Pathology and Interim Chair of Anatomy.
My areas of research include immunology, MHC, antigen processing, T cell, phagocytosis, endocytosis, subcellular fractionation, mycobacteria, tumor immunity, tuberculosis, cell biology, exosomes, and extracellular vesicles.
Research Information
Research Projects
Dr. Harding has been active in developing research training for PhD students, MD-PhD students and physician-scientists, including both basic and translational research training programs. He has designed and launched new training programs in Immunology and Cancer Biology (e.g. as founding Director of the Immunology Training Program at CWRU) and a new Clinical and Translational Scientist Training Program (CTSTP; CTSA TL1 supported). He has contributed to the national/international Immunology research community with service on NIH study sections and through the American Association of Immunologists (e.g. as Chair of the AAI Committee on Public Affairs).
Harding Lab Research
Much of our effort is now directed to understanding regulation of antigen presenting cell (APC) function in the context of infectious diseases, e.g. tuberculosis and HIV infection. APCs sense pathogens by innate immune receptors, including Toll-like receptors (TLRs), and are regulated by cytokines and interferons that are produced during infection. For example, we are studying regulation of APCs by Mycobacterium tuberculosis through TLR2 and the resulting signaling and cytokine responses that contribute to the balance of host defense and immune evasion mechanisms. The following model has been developed from our studies.
Dr. Harding has a long-standing NIH-funded research program on the cell biology of antigen presenting cells (APCs) and their regulation by Toll-like receptors (TLRs) or infection with Mycobacterium tuberculosis (Mtb) or HIV. He has over 190 publications on topics in immunology, cell biology and infectious diseases (>10,500 citations, h-index = 55). His early work included the discovery of exosomes and their genesis by exocytosis of multivesicular exosomes in 1983, and participation in the first study demonstrating that exosomes from APCs contain MHC molecules (1996). In recent years he has published on exosomes released from macrophages, including exosomes from Mtb-infected macrophages that bear bacterial molecules. His work from the 1980’s and 1990’s included fundamental discoveries concerning cell biological and biochemical mechanisms of antigen processing and antigen presentation by MHC-I and MHC-II molecules. His recent research has studied the regulation of APCs, particularly in the context of infection and signaling by innate immune receptors. He has studied the regulation of APCs by TLR2 agonists expressed by Mtb (lipoproteins and glycolipids) and the signaling pathways by which Mtb regulates the balance of inflammatory mechanisms in macrophages and the magnitude and differentiation of T cell responses. These mechanisms may contribute to immune evasion and the persistence of Mtb infection. Other projects have focused on regulation of immune responses by TLR9 and type I interferon.