Richard M. Siegel, M.D., Ph.D.
Building 10, Room 13C103A
10 Center Drive
Bethesda, MD 20814
The goal of the Immunoregulation Group is to understand how alterations in regulatory signaling pathways in immune cells lead to abnormal immune responses, chronic inflammation, and autoimmune diseases. The TNF family of cytokines is the main focus of present work, as these cytokines are critical in the pathogenesis and treatment of a number of different autoimmune and inflammatory diseases. We are particularly interested in how membrane-proximal events in receptor signal transduction can be influenced by environmental or other signals to alter cellular responses, since understanding these principles may aid in designing more effective therapeutic strategies to modulate the effects of TNF-receptor family signaling in autoimmune and inflammatory diseases. The general strategy of the lab is to better understand basic mechanisms of transmembrane signal transduction by selected TNF family receptors using the both cell and molecular biology approaches. We are also interested in studying the role of particular TNF family ligand-receptor systems in immune cells through mouse models.
Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, Kim KY, Sack MN, Kastner DL, Siegel RM. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med. 2011;208(3):519-33.
Ramaswamy M, Cruz AC, Cleland SY, Deng M, Price S, Rao VK, Siegel RM. Specific elimination of effector memory CD4+ T cells due to enhanced Fas signaling complex formation and association with lipid raft microdomains. Cell Death Differ. 2011;18(4):712-20.
Meylan F, Hawley ET, Barron L, Barlow JL, Penumetcha P, Pelletier M, Sciumè G, Richard AC, Hayes ET, Gomez-Rodriguez J, Chen X, Paul WE, Wynn TA, McKenzie AN, Siegel RM. The TNF-family cytokine TL1A promotes allergic immunopathology through group 2 innate lymphoid cells. Mucosal Immunol. 2014;7(4):958-68.
Simon A, Park H, Maddipati R, Lobito AA, Bulua AC, Jackson AJ, Chae JJ, Ettinger R, de Koning HD, Cruz AC, Kastner DL, Komarow H, Siegel RM. Concerted action of wild-type and mutant TNF receptors enhances inflammation in TNF receptor 1-associated periodic fever syndrome. Proc Natl Acad Sci U S A. 2010;107(21):9801-6.
Meylan F, Davidson TS, Kahle E, Kinder M, Acharya K, Jankovic D, Bundoc V, Hodges M, Shevach EM, Keane-Myers A, Wang EC, Siegel RM. The TNF-family receptor DR3 is essential for diverse T cell-mediated inflammatory diseases. Immunity. 2008;29(1):79-89.