Specific Aim 1

Specific Aim 1

Identify novel and subgroup-associated islet autoantigen and therapeutic targets for T1D to innovate potential cures.

Lead Postdoctoral Researcher: Shiva Pathak, PhD, MS

Goals:

  • HLA-typing of bio-banked samples to compare the distribution among Asian individuals compared with other ethnicities.
  • Study different subsets of T regulatory cells (including the CD8 Tregs that we have discovered) among Asian population vs other ethnicities.
  • Find therapeutic targets  for tolerance induction in Type 1 Diabetes.

HLA-type Subjects in DIMC Endo Biorepository to Identify Diabetes-Susceptible HLA-types Among Asians with T1D – Retrospective vs Prospective Analysis

Principal Investigator and Collaborators: Everett Meyer, MD; Kent Jensen, PhD; David Maahs, MD, PhD, MA; Anna Gloyn, DPhil; Holden Maecker, PhD

Objectives: 

  • HLA genes represent 60% of T1D genetic risk. HLA molecules are protein receptors that present fragments of other proteins from inside cells (HLA-class I, expressed by all cells) or taken up from outside cells (HLA-class II) by antigen presenting cells (APCs). Allelic differences in HLA molecules lead to differences in the repertoire of protein fragments (called determinants) presented to CD8 (HLA-class I) or CD4 (HLA-class II) T cells, respectively.
  • Utilize resources from Diabetes Immune Monitoring Core (DIMC) to HLA-type subjects in our T1D biorepository and compare the HLA-alleles extant among Asian (East, South East and Southern), Caucasian and Latin X donor samples, prioritizing Asians.

B & T Cell Receptor (BCR & TCR) Usage in T1D Among Asians in SF Bay Area

Principal Investigator and Collaborators: Holden Maecker, PhD; Everett Meyer, MD; Kent Jensen, PhD

Objectives: 

  • Determine BCR and TCR repertoire usage of autoreactive B and T cells among Asian, comparing Asians (East, South East, Southern) vs. other ethnic groups in the SF Bay Area.
  • Identify novel beta cell antigens that elicit B and T cell responses that contribute to T1D that distinguish Asians from other ethnic groups.