Development of Small Molecule-based Methods for Targeted Cargo Delivery to Beta Cells
Contact PI: Amit Choudhary, PhD, Broad Institute (UC4 DK116255)
Bridget Wagner, PhD, Investigator, Broad Institute
Rohit Kulkarni, MD, PhD, Investigator, Joslin Diabetes Institute
Start Date: September 30, 2017
End Date: September 30, 2021
Abstract
A loss of β-cell mass and biologically active insulin is a key feature of both type 1 and type 2 diabetes. Thus, increasing β-cell mass, for example with small molecules, has become an area of major research interest in the diabetes community. Our groups have recently reported the discovery of small molecules capable of inducing human β-cell proliferation; however, the potential for inducing wide-ranging proliferation across multiple tissues and cell types makes such an approach risky. Here, we aim to develop a prodrug system for targeted β-cell delivery of small molecules that promote β-cell proliferation. This system will enable us to perform early-stage preclinical validation that selective β-cell delivery will be safer and more effective than nonselective systemic administration.
Publications
- Fluorescein-based sensors to purify human α-cells for functional and transcriptomic analyses
- Excess pancreatic elastase alters acinar-β cell communication by impairing the mechano-signaling and the PAR2 pathways
- Rational Design of Silicon-Based Zinc Ionophores
- Harnessing reaction-based probes to preferentially target pancreatic β-cells and β-like cells
- A 3D culture platform enables development of zinc-binding prodrugs for targeted proliferation of β cells
- Engineering designer beta cells with a CRISPR-Cas9 conjugation platform
- Native Zinc Catalyzes Selective and Traceless Release of Small Molecules in β-Cells
- How, When, and Where Do Human β-Cells Regenerate?
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