We apply for renewal of a T32 postdoctoral training program to support 5 postdoctoral trainees studying molecular mechanisms of immunologic tolerance and autoimmunity. Training faculty include a highly interactive group of 28 faculty (among about 70 immunologists and principal investigators in our community) strongly focused on B and T cell development, antigen recognition, repertoire development, silencing by editing, deletion and anergy, and strategies to enhance immunity to tumors. Training is performed at the University of Colorado (UC) and its affiliate National Jewish Health (NJH). All trainers are primary or secondary members of the Department of Immunology & Microbiology and members of the Immunology graduate Program at UC. The number of faculty on this application have increased by 40% since our last competitive renewal, prompting us to increase our request for trainee support from 4 to 5. The increase in faculty reflects recruitment of new faculty to our institution and broadening in areas in which we intend to train, such as tumor immunology and translational research. The program is headed by two Program Directors, Dr. Roberta Pelanda, who has become the co-director in 2017 and will be the primary grant contact, and Dr. John Cambier, who has directed the Program since its inception. These co-directors have expertise in immunological tolerance and autoimmunity with studies in both mice and humans. Dr. Pelanda is also the Director of the hematopoietic humanized mouse core facility, while Dr. Cambier has trained more than 60 postdocs and graduate students, and is a Distinguished Professor and Chairman of the Department of Immunology and Microbiology and the Director of the UCSOM Human Immunology and Immunotherapy Initiative. Postdoctoral fellows will be selected for support by the Recruitment and Appointing Committee after application by the trainee and mentor. Selection will be based on merit and research proposed. Trainees will be required to take a course in the Responsible Conduct in Research, to attend and present once a year in our weekly ?Research in Progress? forum, and to complete each year an Individual Development Plan. Evaluation of progress of research and career guidance will be provided by a mentoring committee consisting of at least 3 faculty members and meeting with the trainee once every 6 months. The goal of this training program 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. This Training Program continues to be a major focus for immunological research in the Rocky Mountain region in particular and the USA in general.

Public Health Relevance

Autoimmunity is a constellation of about 100 chronic debilitating diseases estimated to afflict >50 million of Americans with treatment costs exceeding $100 billion. Among the top 10 causes of death, these diseases exact an enormous social and economic toll. 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 five post-doctoral fellows while they receive research training in the molecular basis of immune tolerance and autoimmunity, and how tolerance may be undermined to enhance immune responses to tumors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Institutional National Research Service Award (T32)
Project #
2T32AI074491-11
Application #
9804163
Study Section
Allergy, Immunology, and Transplantation Research Committee (AITC)
Program Officer
Gondre-Lewis, Timothy A
Project Start
2009-08-01
Project End
2024-06-30
Budget Start
2019-07-08
Budget End
2020-06-30
Support Year
11
Fiscal Year
2019
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

Showing the most recent 10 out of 59 publications