Autoimmunity & Lymphoid Organs

Lymph Node

Lymph Node

Lymph node high endothelial venule from a mouse genetically engineered to express a green fluorescent protein.

About this image…

Dr. Ruddle’s laboratory focuses on understanding mechanisms of cell trafficking in inflammation and lymphoid organ development, particularly through high endothelial venules and lymphatic vessels. The laboratory studies mouse models of several autoimmune diseases including multiple sclerosis, type 1 diabetes, and Sjogren’s syndrome. Recent studies have also focused on human tissues from Sjogren’s syndrome. Much of Ruddle’s work has focused on the concept of “ectopic” or “tertiary” lymphoid tissues that arise in chronic inflammation in autoimmune diseases, infections, and graft rejection, in an effort to relate this phenomenon to the normal development of lymphoid organs. The goal of the laboratory is to utilize the knowledge gained through these areas of research in the rational design of prevention and therapeutics for autoimmune diseases. 

Projects

  • Lymphotoxin and Lymphoid Neogenesis
  • MOG expression in lymphoid organs; regulation and functional consequences: The goal of this project is to evaluate the biochemical nature, regulation, and effect of inflammation on MOG expression in cells from lymphoid organs.
  • Juvenile Diabetes Research Center for developing immune therapies for Type 1 diabetes: The goal of the project is to develop a humanized mouse for the study of Type 1 diabetes.
  • Yale Autoimmunity Center of Excellence: The goal of the project is to establish a new Autoimmunity Center of Excellence that will involve clinical and basic investigators with expertise in clinical trials, translational medicine, basic immunology, and bioengineering to develop new therapeutic approaches for the  autoimmune diseases based on understanding of the mechanisms involved and targeting pathways that lead to tissue destruction. 
  • Lymphatic Vessel Imaging

Publications

  • Truman LA, Bentley K, Smith E, Massaro S, Gonzalez DG, Haberman A, Hill M, Jones D, Min W, Krause D, Ruddle NH. Prox Tom lymphatic vessel reporter mice reveal Prox1 expression in the adrenal medulla, megakaryocytes, and platelets. Am. J. Pathol. April 2012 (in press).
  • Liao S, Cheng G, Connor DA, Huang Y, Kucherlapati RS, Munn LL, Ruddle NH, Jain RK, Fukumura D, Padera TP. Impaired lymphatic contraction associated with immunosuppression. PNAS 108:18784-9, 2011. PMID:22065738.
  • Motallebsadeh RM, Rehakova S, Conlon T, Win TS, Callaghan CJ, Goddard M, Bolton EM, Ruddle NH,  Bradley JA, Pettigrew GJ. Blocking lymphotoxin signaling abrogates the development of ectopic lymphoid tissue within cardiac allografts and inhibits effector antibody responses. FASEB J. 2011, Sep 16 [Epub ahead of print] PMID:21926237.
  • Bentley KL, Stranford S, Liao S, Mounzer RH, Ruddle FH, Ruddle NH. High endothelial venule reporter mice to probe regulation of lymph node vasculature. Adv. Exp. Biol. 691:35-44, 2011. PMID:21153307
  • Akirav EM, Ruddle NH, Herold, KC. The role of AIRE in human autoimmune disease. Nat. Rev. Endocrinol. Nat Rev Endocrinol. 7:25-33, 2011. PMID: 21102544 [PubMed - in process]
  • Mounzer, R.M. Mounzer RH, Svendsen OS, Baluk P, Bergman CM, Padera TP, Wiig H, Jain RK, McDonald DM, Ruddle NH. Lymphotoxin alpha contributes to lymphangiogenesis. Blood 116:2173-82, 2010. PMCID:PMC2951858.
  • Bentley, KL, Shashikant, CS, Wang, W, Ruddle, NH, Ruddle, FH. A yeast-based recombinogenic targeting toolset for transgenic analysis of human disease genes of interest.  Annals of the NY Acad. Sci.,Suppl 1:E58-68, 2010. PMID: 20961307
  • Ruddle, N.H. and Akirav, E.M. Secondary Lymphoid Organs:  Responding to Genetic and Environmental Cues in Ontogeny and the Immune Response.  J Immunol. 183:2205-2212, 2009. PMCID: PMC2766168