The pervasive influence of the immune system on human health and disease underscores the importance of mechanistic understanding of immune regulation under pathophysiological conditions. Modern immunology is built on the foundation of clonal selection and pattern recognition theories that emphasize innate and adaptive immune recognition in controlling immune responses.
Despite the compelling power of these theories to explain how adaptive immune responses to infectious microorganisms are initiated, the means by which antigen and inflammatory signals propagate to induce growth, proliferation, and differentiation of lymphocytes are not completely understood. In addition, these paradigms do not fully address how autoreactive lymphocytes are tolerized, how naïve and memory lymphocytes are maintained in the absence of cognate antigens, and how immune responses are regulated in the context of (non-classical scenarios of antigen exposure such as) cancer.
We have postulated that regulatory mechanisms, established by co-opting evolutionarily ancient cell signaling and cell metabolism modules, work in concert with innate and adaptive sensing mechanisms to ensure well-ordered immune activities. To this end, studies from my laboratory have led to the elucidation of critical roles for TGF-beta, Foxo, Notch, nutrient sensing, and nutrient metabolism pathways in the control of T lymphocyte development, homeostasis, tolerance, immunity, and memory, as well as innate and adaptive immune responses to cancer. A major current focus in the lab is to study how cell signaling and cell metabolism modules are rewired in the immune system using diverse immunological, genetic, biochemical, and genomic approaches, and to exploit these regulatory pathways for disease therapy including cancer immunotherapy.