Molecular characterization of STK25 as a novel regulator of energy homeostasis via the Hippo and mTOR signaling pathways

Project: Research

Investigators

  • Sanghee Lim (PI)

Description

Type II Diabetes Mellitus (T2DM) is a complex metabolic disorder that has seen a meteoric rise in recent years as a combination of lifestyle factors and genetic contributors have resulted in a pandemic of unseen proportions. A central aspect of T2DM is deregulation of critical signaling pathways that ultimately result in the inability of cells to appropriately respond to physiologic fluctuations in nutrient availability. However, the molecular intermediaries responsible for maintaining such energy homeostasis remain poorly characterized. The kinase STK25 has been implicated in numerous metabolic disorders, including T2DM and fatty liver disease. However the underlying mechanism remains completely uncharacterized. The goal of this proposal is to define STK25 as a novel regulator of energy homeostasis vis-a-vis its effects on two critical signaling pathways - the Hippo tumor suppressor pathway and the mTOR pathway. We have recently identified STK25 as playing a previously unappreciated role in regulating Hippo signaling (Figures 1 and 3), and its loss promotes the expression of critical regulators of glucose transport and metabolism (Figure 2). Furthermore, we unexpectedly discovered a role for STK25 in regulating mTOR signaling in response to nutrient availabilities (Figure 4). As such, the overall hypothesis is that STK25 regulates energy homeostasis by coordinately promoting Hippo and mTOR activation under normal physiologic fluctuations of nutrients, which will be tested by addressing the following two specific aims: 1) Mechanistically define how the STK25-Hippo signaling axis controls glucose homeostasis; 2) Determine the role of STK25 in regulating mTOR signaling in response to nutrient availability. Our experimental approaches will integrate a combination of cell and molecular biology, biochemistry, bioinformatics, and in vivo experimentation to conclusively address the overall hypothesis.
Award amount$26,844.00
Award date01/01/2019
Program typePredoctoral Fellowship
Award ID19PRE34370004
Effective start/end date01/01/201912/31/2019
StatusFinished