The BDC-JDRF Autoimmunity Prevention Center at University of Colorado at Denver and Health Sciences Center


Director: John C. Hutton, Ph.D.


Objective

The Barbara Davis Center for Childhood Diabetes (BDC) is a leading international research institution affiliated with the University of Colorado Health Sciences Center with a focus on type 1 diabetes treatment and prevention.

Background/Rationale

BDC has a long tradition of collaborative research, (ITN, DPT, TRIALNET, SEARCH, TEDDY, Brehm Coalition), generation and sharing of novel research reagents (T-cell clones BDC 2.5, 6.9 and 10.1, Phogrin P2/P7; autoantigens (IGRP, Phogrin and ZnT8), transgenic mice (insulin B16AlaNOD and IGRP-/-NOD), and human genes (PTPN22 and DQB1 0602 recombinants). Its website hosts the Genespeed bioinformatics resource genespeed.uchsc.edu, and seminal publications including Peter Chase’s “Understanding Diabetes” and the “Immunology of Diabetes” edited by George Eisenbarth www.barbaradaviscenter.org. The BDC recently expanded 4 fold and occupies a 125,000 sq ft. building that accommodates T1D clinical care, clinical research, translational research and basic research under the same roof alongside Computational Biology (Larry Hunter), Autoimmunity Research (Mike Holers) a Research Infusion unit and an Islet Transplantation Immunobiology unit incorporating a GMP facility (Alex Wiseman).

Description of Project

The establishment of a JDRF Autoimmunity Center Grant at this time will build upon the achievements of the BDC, will facilitate recruitment of researchers, the development of new technologies, and accelerate the design of safe interventions to prevent or slow the progression of type 1 diabetes. Importantly, the latter will be based upon a mechanistic understanding of immune-based therapies.

Anticipated Outcomes

The JDRF Center proposal focuses on two ß cell-specific autoantigens (insulin and ZnT8) that hold promise as components of therapeutic agents with minimal off-target drug effects. Three research projects and 2 clinical trials are outlined: the research component to gain insight into the role of the molecules in the pathogenesis of type 1 diabetes defined at the cellular and molecular level; the trials to implement antigen-specific therapies in human subjects aimed at restoration of immune tolerance. Besides an Administrative Core, a biomedical resource core is proposed that will service the basic and clinical research components and at the same time develop procedures to monitor the effectiveness of therapies interventions and disease recurrence.

Project 1: Evaluation of a conserved alpha chain T-cell receptor clonotype (P.I. Eisenbarth)

Project 5: Humoral autoreactivity to the novel T1D autoantigen Slc30A8 (P.I. Hutton)

Project 6: T-cell immunity to the novel T1D autoantigen Slc30A8 (P.I. Davidson)

Project 8: Pre-Point Immune Response Monitoring (P.I. Gottlieb)

Core A: Lymphocyte Analysis Core (P.I Zipris)

Core B: BDC JDRF Autoimmunity Prevention Center Administrative Core (Director Hutton)

A 5-year plan is proposed with a budget of $6.5M direct costs. Each project will span for 4 to 5 years and provision is made for additional studies funded by annually awarded pilot and feasibility grants of up to $100K. Operation of the Center will be managed by an Executive committee headed by Dr. Hutton and comprised of the PI’s with governance from an Advisory committee of national scientific experts and JDRF scientific and lay committee members.