We request renewed support for a postdoctoral training program focused on molecular mechanisms of immunologic tolerance and autoimmunity. The application comes from a highly interactive faculty centered in the Integrated Department of Immunology whose faculty is strongly focused on B and T cell development, antigen recognition, repertoire development, silencing by editing, deletion and anergy, and understanding autoimmunity. The Integrated Department of Immunology is comprised of 65 faculty (primary and secondary) from three institutions: the National Jewish Health, The Barbara Davis Center for Childhood Diabetes (BDC) and The University of Colorado School of Medicine. Nearly half of the 20 training faculty have been recruited to the Department since its inception in 1999, and all training faculty are supported by NIH RO1 grants on which they are Principal Investigator. We request stipend support for 4 fellows who will train in laboratories of their choosing whose research is focused of immune tolerance and autoimmunity. The fellows will participate in regularly scheduled journal clubs, research in progress seminars, formal seminars and courses, e.g. on ethics and survival skills in science, and their progress will be monitored by a training oversight committee (TOC). Trainees will be appointed for one year and reappointed only if they are judged by the TOC to be making significant progress. Our goal is to provide fellows with comprehensive knowledge of immune tolerance and mouse models of autoimmunity, and sufficient understanding of clinical autoimmunity to enable their development of productive clinical collaborative ties for translation of research. The Program Director is Dr. John Cambier, Ida and Cecil Green Distinguished Professor and Chairman of the Integrated Department of Immunology. Dr. Cambier is an expert in B cell signaling, activation and anergy, and has trained in excess of 60 graduate students and postdoctoral fellows. The training program has available superb research facilities and the faculty, are interactive in both training and research. Although the Denver immunology community has been training pre- and postdoctoral fellows for over 30 years, formation of the Integrated Department of Immunology and hiring of new faculty has provided a strongly uniting influence, and injected new excitement and vitality into our educational and research activities. This training program is a central focus of that vitality.

Public Health Relevance

Autoimmunity is a constellation of >80 diseases estimated to afflict 20% of Americans. Among the top 10 causes of death, these diseases exact an enormous social and economic toll. Autoimmunity is estimated to have an economic impact of hundreds of billions of dollars per year. Knowledge of the molecular mechanisms that maintain immunologic tolerance and how they fail in autoimmunity is sadly lacking. Thus, we request renewal of T32 AI074491 to support stipends of four post-doctoral fellows while they receive research training across the continuum from repertoire development and the molecular basis of immune tolerance, to clinical autoimmunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Institutional National Research Service Award (T32)
Project #
5T32AI074491-07
Application #
8877393
Study Section
Allergy, Immunology, and Transplantation Research Committee (AITC)
Program Officer
Gondre-Lewis, Timothy A
Project Start
2007-07-01
Project End
2019-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
7
Fiscal Year
2015
Total Cost
Indirect Cost
Name
National Jewish Health
Department
Type
DUNS #
076443019
City
Denver
State
CO
Country
United States
Zip Code
80206
Wang, Yang; Sosinowski, Tomasz; Novikov, Andrey et al. (2018) C-terminal modification of the insulin B:11-23 peptide creates superagonists in mouse and human type 1 diabetes. Proc Natl Acad Sci U S A 115:162-167
Sang, Allison; Danhorn, Thomas; Peterson, Jacob N et al. (2018) Innate and adaptive signals enhance differentiation and expansion of dual-antibody autoreactive B cells in lupus. Nat Commun 9:3973
Klarquist, Jared; Chitrakar, Alisha; Pennock, Nathan D et al. (2018) Clonal expansion of vaccine-elicited T cells is independent of aerobic glycolysis. Sci Immunol 3:
Liu, Haolin; Wang, Chao; Lee, Schuyler et al. (2018) Specific Recognition of Arginine Methylated Histone Tails by JMJD5 and JMJD7. Sci Rep 8:3275
Schroeder, Kristin M S; Agazio, Amanda; Strauch, Pamela J et al. (2017) Breaching peripheral tolerance promotes the production of HIV-1-neutralizing antibodies. J Exp Med 214:2283-2302
Rubtsova, Kira; Rubtsov, Anatoly V; Thurman, Joshua M et al. (2017) B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. J Clin Invest 127:1392-1404
Vanoni, Simone; Tsai, Yi-Ting; Waddell, Amanda et al. (2017) Myeloid-derived NF-?B negative regulation of PU.1 and c/EBP-?-driven pro-inflammatory cytokine production restrains LPS-induced shock. Innate Immun 23:175-187
Salinas, Gustavo; Gao, Wei; Wang, Yang et al. (2017) The Enzymatic and Structural Basis for Inhibition of Echinococcus granulosus Thioredoxin Glutathione Reductase by Gold(I). Antioxid Redox Signal 27:1491-1504
Liu, Haolin; Wang, Chao; Lee, Schuyler et al. (2017) Clipping of arginine-methylated histone tails by JMJD5 and JMJD7. Proc Natl Acad Sci U S A 114:E7717-E7726
Schroeder, Kristin Ms; Agazio, Amanda; Torres, Raul M (2017) Immunological tolerance as a barrier to protective HIV humoral immunity. Curr Opin Immunol 47:26-34

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