Jingshi Shen, Assistant Professor

Research Interests:

Signal transduction across membranes; Auto-feedback cellular homeostasis systems.

Research Profiles:

1. Regulation of GLUT4 Exocytosis

Regulated transport of membrane proteins to the plasma membrane is essential for nutrient and energy balance.  One prominent example is the insulin-triggered glucose transporter 4 (GLUT4) exocytosis.  Following a meal, insulin promotes the uptake of glucose into adipocytes and muscle cells by relocating GLUT4 from intracellular reservoirs to the cell surface.   Imbalances in this coupled transport result in insulin resistance and type 2 diabetes.  Insulin appears to modulate multiple stages of GLUT4 trafficking, in which vesicle fusion (merging of GLUT4-containing vescles with the plasma membrane) has recently been found to be a key regulatory step.  The coupling mechanisms of vesicle fusion with insulin signaling remain largely unknown due to a lack of mechanisitic studies in minimal functional systems.  We are addressing this problem from a novel angle by reconstituting GLUT4 exocytosis in vitro with purified components.  We also aim to directly visualize the exocytic complex by electron microscopic tomography at Boulder's 3D EM Laboratory housed in MCDB.  Our long-term vision is to understand a) how protein-protein networks control the membrane trafficking of GLUT4 and b) how imbalances cause glucose intolerance and diabetes.

2.  Proteolytic processing of membrane-tethered transcription factors

A novel class of transcription factors such as SREBP and ATF6 are synthesized as membrane-bound precursors and are activated by regulated intramembrane proteolysis (RIP).  These factors directly couple the perturbations of membrane environments to gene expression programs in the nucleus.  We aim to understand the regulatory mechanisms of the proteolytic processing involved and how imbalances cause major forms of disease including diabetes and Alzheimer's disease.