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Arya Nakhe

Graduate Student, Jacobson Laboratory, Molecular Physiology and Biophysics

I grew up in Kolhapur, India and received my bachelor’s degree in Biotechnology Engineering from Shivaji University, India. Following graduation, I moved to Philadelphia to pursue a master’s degree in Biotechnology at the University of Pennsylvania where my research focused on genetic variation affecting transcriptional regulation of hepatic metabolism by the nuclear receptor PPARα.

Currently, I work in the Jacobson lab studying the mechanistic role of pancreatic ion channels in health and diabetes. My thesis project focuses on developing pharmacology for the pancreatic two-pore domain K+ channel TALK-1. β-cell TALK-1 functions on the plasma membrane and the ER membrane culminate in limiting glucose-stimulated Ca2+ oscillation frequency and pulsatile insulin secretion. KCNK16, the gene that encodes TALK-1, is the most islet-restricted and most abundant β-cell K+ channel transcript. Furthermore, a T2D associated non-synonymous polymorphism (rs1535500) in KCNK16 that causes a gain-of-function (GOF) in TALK-1 may reduce β-cell Ca2+ entry and insulin secretion. Another GOF mutation in TALK-1 (>300X), L114P, causes autosomal dominant maturity onset diabetes of the young (MODY) by reducing glucose-stimulated β-cell Ca2+ influx (GSCI), [Ca2+]ER storage and insulin secretion. Together these data suggest that TALK-1 is an islet-restricted therapeutic target and inhibition of TALK-1 channels could increase Ca2+ oscillation frequency, pulsatile insulin secretion and [Ca2+]ER storage in T2D with minimal off-target effects. My research utilizes a wide range of techniques including high-throughput screening approaches, Ca2+ imaging and electrophysiological recordings to identify and optimize TALK-1 inhibitors and to investigate the therapeutic potential of inhibiting TALK-1 in the treatment of diabetes.

When I’m not in lab, I enjoy painting, music, cooking and traveling.