Our laboratory is primarily interested in the mechanism of immune regulation by innate immunity in the context of tumors, infections and autoimmune diseases. By understanding how the immune system deals with microbes, tumors, and self, we aim to design effective vaccines and therapeutics against cancer and infectious diseases. Presently our study focuses on two classes of proteins: heat shock proteins (HSPs) and Toll-like receptors (TLRs), both of which have been implicated as master regulators of immunity. We, and others, have discovered that the function of TLRs is dependent on the integrity of the HSP gp96 (or grp94) in the endoplasmic reticulum. Furthermore, depending on its expression level and its subcellular localization, gp96 can initiate systemic autoimmune disease as well as tumor-specific immunity, both of which have a significant clinical relevance. Using a combination of genetic, cell biological, biochemical and immunological tools, we aim to pinpoint the precise mechanism of TLR-gp96 interaction and define the functions of gp96 in hematopoiesis and in the functions of various cellular components in the immune system. In addition, since gp96 is also an important molecule in mediating the unfolded protein response (UPR), works are ongoing to dissect the roles of gp96 in organ development and oncogenesis, and to develop gp96-specific inhibitors for the treatment of diseases with a heavy pathogenic component of inflammation and metabolic dysregulation. Our study has a broad implication in understanding how the immune system operates physiologically and during pathological conditions, in light of the critical roles of TLRs and the UPR in the evolution, function and regulation of the immune response.
Our laboratory has also developed interests in the study of the regulation of both normal and cancer stem cells; particularly hematopoietic stem cells, gut stem cells and cancer stem cells. In a potential paradigm-shifting work, our group discovered that transplantation of human embryonic stem cells is able to stimulate a cross-reactive immune response against cancer in mice. Studies are ongoing to discover shared antigens between tumor cells and stem cells, and to understand the mechanism by which normal and cancer stem cells are perceived and dealt with by the immune system, with the hope of launching clinical studies of a stem cell-based cancer vaccine soon. The stem cell-based cancer vaccine is pursued jointly with our long-time collaborator Dr. Bei Liu.
Learn more about how researchers at MUSC are harnessing the body’s own immune system to fight cancer in this informational video.
We take pride in sharing our expertise with trainees at all levels including graduate students, medical residents, clinical fellows and postdoctoral fellows. Trainees are expected to be original, hardworking, independent, and interactive. They are encouraged to choose projects under the general conceptual frame as outlined above and are expected to function at a high level.
We are always seeking exceptionally motivated students and postdoctoral fellows to share our passion in research. Send your CV and description of your research interests to Dr. Li.