Nancy Ruddle, Ph.D.

Professor of Epidemiology and Public Health (Microbial Diseases) and Immunobiology John Rodman Paul Professor of Epidemiology, Public Health and Immunobiology Director of Graduate Studies, Epidemiology and Public Health

Research Interests

My laboratory studies cell trafficking and inflammation in autoimmunity and lymphoid organ development. We are especially interested in members of the lymphotoxin/tumor necrosis factor (LT/TNF) family. We have studied the roles of these and other cytokines in murine models of autoimmune and infectious diseases in part by exploiting transgenic and knock-out mouse technologies. We are particularly interested in chronic inflammation, and we have evaluated the roles of cytokines in inducing adhesion molecules and chemokines in these contexts in several organs, including the skin, the central nervous system, the pancreas, and the lung. We study the role of the LT/TNF molecules in acute inflammation and animal models of autoimmune diseases, including Type 1 diabetes mellitus and multiple sclerosis (MS). We can distinguish between different pathogenic mechanisms in experimental autoimmune encephalomyelitis (EAE), the MS model; antibody is pathogenic in EAE only when it recognizes a glycosylation dependent epitope on myelin oligodendrocyte glycoprotein. These studies have implications for diagnosis and treatment of MS patients characterized by different pathogenic mechanisms. LT is also crucial in lymphoid organ development; LT deficient mice lack lymph nodes and exhibit profound alterations in spleen, nasal associated lymphoid tissue, and Peyer's patches. Our studies demonstrate that the roles of the cytokines in lymphoid organ development and inflammation are similar in that they regulate chemokines and vascular adhesion molecules. Ectopic or "tertiary" lymphoid organs arise in chronic inflammation. These lymphoid accumulations, which arise through a process termed lymphoid organ neogenesis, permit the presentation of foreign or auto-antigens at local sites of inflammation. Our most recent studies have concentrated on the regulation lymphoid organ vasculature, both high endothelial venules and lymphatic vessels, in lymph nodes and inflammation. Our studies elucidate basic developmental mechanisms and also point the way towards treatment and prevention of chronic inflammation.

Recent Publications

• Marta, C.B., Oliver, A.R., Sweet, R.A. Pfeiffer, S.E., Ruddle, N.H. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology. PNAS 102:13992-13997, 2005
• Drayton, D.L., Liao, S., Mounzer, R.H., Ruddle, N.H. Lymphoid organ development: from ontogeny to neogenesis. Nat. Immunol. 7:344-353, 2006
• Liao, S., Ruddle, N,H. Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J. Immunol. 177:3369-79, 2006
• Liao, S., Bentley, K., Lebrun, M., Lesslauer,W., Ruddle, F.H, Ruddle, N.H. Transgenic lacZ under control of hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules. PNAS, in press, 2007

Contact

Campus Address:	131H Amistad Building, 10 Amistad Street
Mailing Address:	Epidemiology & Public Health and Immunobiology Yale University School of Medicine, PO BOX 208089 New Haven, CT 06520-8089
Phone:	(203) 785-2915
E-mail:	Nancy.Ruddle@yale.edu