Neelanjan Mukherjee, PhD
Associate Professor
University of Colorado School of Medicine
Featured in the Session: Lessons from Islet Biology for Next-Generation Therapies
When
Sunday, June 7
at 4:30 p.m.
Where
355 (Level 3)
Ernest N. Morial Convention Center
What is your presentation about?
Growing evidence supports the idea that beta cell dysfunction precedes clinical diagnosis and may contribute to disease pathogenesis. One model that explains how beta cells become immunogenic is the defective ribosomal product (DRiP) hypothesis, which proposes that errors in translation, such as frameshifting or premature termination, that generate aberrant proteins that are rapidly processed and presented on MHC class I. For example, beta cells produce a non-canonical product derived from the insulin gene (INS-DRiP), which has been shown to activate insulin-specific CD8+ T cells. Our study employed a proteogenomic approach, integrating RNA-seq, Ribo-seq, and proteomics, to identify novel proteins and potential DRiPs in human beta cells as well as novel translational regulation during beta cell differentiation.
How do you hope your presentation will impact diabetes research or care?
The presentation aims to provide the diabetes research community with a translatome resource that expands the known “dark proteome” of the beta cell, offering new insights into beta cell biology and autoimmune mechanisms. By identifying novel immunogenic peptides presented on the beta cell surface, this work facilitates the discovery of autoreactive T-cell receptors (TCRs) and informs the development of future therapeutic strategies for immune protection and disease intervention.
How did you become involved with this area of diabetes research or care?
My training is in RNA systems biology and I had not done any diabetes or β-cell research before this work. Two trainees were the catalyst and drivers of this research: Dr. Roberto Castro-Gutierrez (a PhD student in the lab of Dr. Holger Russ) and Dr. Kathryn Walters (a PhD student in my lab).