The immune system is among the most complex and important organ systems in the human body. In addition to protecting against infectious microorganisms, the immune system, in particular spurious or uncontrolled inflammation, is now linked to nearly all major human pathologies, from autoimmunity and cancer to metabolic syndrome and neurodegenerative diseases. Most aspects of inflammation are coordinated by CD4+ T cells, which produce select cytokines following their differentiation from naïve precursors into a variety of pro- or anti-inflammatory subsets. These cytokines direct the growth, recruitment and differentiation of other immune cells, and they can also directly provoke inflammatory gene expression in tissue parenchyma. Better understanding of the development, diversity, and function of T cell subsets is essential to improve the therapeutic landscape for patients with immune-mediated inflammatory diseases. Conversely, these same principals can also be harnessed to exploit the power of the inflammatory response to kill extant tumors.
We are focused on identifying novel T cell subsets associated with clinical inflammatory syndromes and dissecting signaling circuits that regulate their development and deleterious function. We are particularly interested in the role of IL-17-secreting CD4+ T cells (i.e., Th17 cells) in health and disease, and in amino acid-responsive signaling pathways, which we have shown limits chronic inflammation by selectively blocking Th17 cells. The Sundrud lab exploits both human and mouse systems in parallel; we are exploring T cell biology in both clinical/translational settings, as well as in validated mouse models. In addition, the lab seeks to identify novel chemical probes via high-throughput cell-based and molecular screens, in order to dissect signaling pathways in ways not possible through conventional mouse genetics. These screens may also identify new lead molecules that can be developed into selective T cell-targeted therapies.