Thematic Areas of Research
This is a broad-based training program that reflects the research interests of faculty at MUSC engaged in Immunology research. Research at MUSC centered on immune-mediated pathogenesis covers all three basic areas of immunology, namely innate immunity, T cell biology, and antibodies/B cell biology. Disease related themes that comprise this program are immunity to infection, alloimmunity (organ and hematopoietic stem cell transplant), autoimmunity, cancer immunity, and various sterile inflammatory conditions (see Figure 1).
Within this relatively broad base of investigation, a central theme of investigating the interplay between the innate and adaptive immune systems has emerged. These two arms of immunity are not only closely linked with regard to cause and effect, but are in fact one entity of the host defense mechanism; fundamental understanding of one is not possible without understanding the other. A research environment to emphasize and unify the two branches of immunology is essential for the development of novel strategies to suppress inflammatory tissue injury, as well as to alter adaptive immune responses.
Half of the Program Faculty are directly involved in research aimed at better understanding of mechanisms that bridge innate and adaptive immune responses. Examples of studies that directly address this link include: How complement and pathogen recognition receptors such as TLRs and C-type lectins modulate the development of humoral and cellular immune responses in the context of auto-, allo- and cancer immunity; How immune modulatory mechanisms are altered as a result of inflammation and premalignant lesions, and how these alterations promote progression to cancer; NK cells, NKG2D biology and cancer immunoediting, CD4 and CD8 T cell polarization and immune tolerance; Cytokine mediated balances between anti-tumor immune response andpro-tumorigenic inflammation; Macrophage biology and its impact on T cell responses in the context of cancer and infection; Antibody dependent cellular cytotoxicity mediated by innate immune cells with effector molecules (antibodies) of the adaptive immune system; How inflammation and innate immune mechanisms resulting from tissue injury or organ dysfunction modulate subsequent alloimmune responses and graft tolerance; How innate immune receptors modulate mucosal immune tolerance; Interaction between products of inflammation and autoantibody production in autoimmune diseases; Regulation of GVHD and GVL through co-stimulatory and co-inhibitory molecules orchestrated by innate immune signals.
Research Foci in this Program Include
- Mechanisms of Inflammation: Biology of the complement system; TLR biogenesis and roles of molecular chaperones in inflammation; mitochondrial biology and dysfunction; neuroinflammation. There is also a mouse smoking facility with equipment for smoking and lung analysis within the Department of Microbiology and Immunology, allowing unique lines of research into smoke-induced lung inflammation and associated diseases. In addition, MUSC has a unique gnotobiotic core to allow the study of the roles of microbes in shaping host immune defense mechanisms and inflammation in a variety of disease settings.
- Host Defense: Immunogenetic approaches to understanding mechanisms underlying the involvement of Ig Fc and Fc receptors in infectious disease, assisted by an exceptional biostatistics services available through the Hollings Cancer Center and MUSC’s CTSA
- Autoimmunity: The superb clinical research program in autoimmunity at MUSC, together with an existing NIH P60 center grant (on Health Disparity in Inflammation and Fibrosis), bring a unique perspective to research into this area.
- Alloimmunity and Transplantation: CD4 T cells; Ischemia reperfusion injury; Mechanisms of inflammation-mediated modulation of alloimmune response; Natural antibodies and organ inflammation and transplant rejection, studies into which have been greatly assisted by the development (and subsequent commercialization) of unique site-targeted complement inhibitory reagents. Mentor faculty also developed a mouse brain death model to study the effect of brain death on post-transplant inflammation and alloimmunity, and we remain one of only two centers in the country able to perform this technique.
- Cancer Immunology: T cell biology and therapy, with unique investigations into TCR transfer, and novel co-stimulatory pathways (ICOS) and cytokine complex in adoptive T cell therapy; Innate immune mechanisms within the tumor environment and modulation of anti-tumor immunity by metabolic stress and chaperones. Unique aspects of this research include TLR chaperone biology, NK cell activation via NKG2D and the biology of NKG2D ligand shedding, TGF regulation of B cells, and complement-dependent anti-tumor mechanisms, and graft-versus-tumor biology post allogeneic hematopoietic stem cell transplantation. Notably, within the Hollings Cancer Center at MUSC (a NCI designated cancer center), Cancer Immunology is one of the four research programs with >$5.5m direct extramural funding in 2013.