Robert Hsiu-Ping Chow

Associate Professor,
Dept. of Physiology & Biophysics
Zilkha Neurogenetic Institute
Keck School of Medicine

Research Topics

  1. Exocytosis
  2. Synaptic transmission
  3. SNARE proteins
  4. diabetes
  5. pancreatic beta cell
  6. insulin secretion

Research Overview

The aim of my laboratory is to advance our understanding of how hormone and neuronal secretion is controlled in normal and pathological states. In the last decade, neuroscience has benefited tremendously from the molecular biology revolution. Dozens of synaptic proteins have been cloned. One of the most exciting goals today is to figure out how these proteins orchestrate the complex life cycle of the secretory vesicle. It is of particular interest to understand how calcium is involved. Katz and colleagues showed that calcium triggers fast exocytosis. More recently it has become clear that calcium may play other important roles that precede exocytosis, perhaps facilitating translocation, docking and priming of vesicles.

One preparation we work with is adrenal chromaffin cells. These neuroendocrine cells, like neurons, fire action potentials, exhibit fast calcium-dependent exocytosis, and express synaptic proteins or closely related proteins. They have the advantages of being easy to prepare, and their secretory vesicles are larger than synaptic vesicles and can therefore be visualized more readily. We use viral vectors to express the protein of interest in native or mutated form, and we then study the effects on secretion. The high-resolution methods we use to monitor exocytosis include membrane capacitance measurements, carbon-fiber amperometry, and total internal reflection fluorescence microscopy (also called evanescent-wave microscopy).

Another related area of interest of the laboratory is the cellular mechanism of abnormal secretion and cell death in diabetes mellitus. In collaboration with Prof. Richard Bergman, we are studying insulin secretion from healthy and diseased pancreatic beta cells. The aim is to understand the nature of derangements in beta cell function early in disease, which may permit design of therapeutic interventions early in the development of type I and II diabetes.

Selected Publications

View a complete PubMed search

View a complete Google Scholar search

Cho JH, Chen L, Kim MH, Chow RH, Hille B, and DS Koh. (2010) Characteristics and functions of {alpha}-amino-3-hydroxy-5-methyl-4-isoxaxoleproprionate receptors expressed in mouse pancreatic {alpha}-cells. Endocrinology 151(4):1541-50. -PubMed

Behrend MR, Ahuja AK, Humayun MS, Weiland JD, Chow RH. (2009) Selective labeling of retinal ganglion cells with calcium indicators by retrograde loading in vitro. J Neurosci Methods. 179(2):166-72. -PubMed

Imoukhuede PI, Moss FJ, Michael DJ, Chow RH, Lester HA. (2009) Ezrin mediates tethering of the gamma-aminobutyric acid transporter GAT1 to actin filaments via a C-terminal PDZ-interacting domain. Biophys J. 96(7):2949-60. -PubMed

Cai H, Reim K, Varoqueaux F, Tapechum S, Hill K, Sorensen JB, Brose N, and RH Chow. (2008) Complexin II plays a positive role in Ca2+-triggered exocytosis by facilitating vesicle priming. Proc Natl Acad Sci USA. 105(49):19538-43. -PubMed

Michael DJ, Xiong W, Geng X, Drain P, Chow RH. (2007) Human Insulin Vesicle Dynamics During Pulsatile Secretion. Diabetes. Feb 22 -PubMed

Michael DJ, Cai H, Xiong W, Ouyang J, Chow RH. (2006) Mechanisms of peptide hormone secretion. Trends Endocrinol Metab.(10):408-15. -PubMed

Michael DJ, Ritzel RA, Haataja L, Chow RH. (2006) Pancreatic beta-cells secrete insulin in fast- and slow-release forms. Diabetes. 55(3):600-7. -PubMed

Michael DJ, Geng X, Cawley NX, Loh YP, Rhodes CJ, Drain P, Chow RH. (2004) Fluorescent cargo proteins in pancreatic beta-cells: design determines secretion kinetics at exocytosis. Biophys J. 87(6):L03-5. -PubMed

Peti-Peterdi J, Fintha A, Fuson AL, Tousson A, Chow RH. (2004) Real-time imaging of renin release in vitro. Am J Physiol Renal Physiol. 287(2):F329-35. -PubMed

Duncan RR, Greaves, J, Wiegand UK, Matsekevich I, Bodammer G, Apps DK, Shipston MJ, and RH Chow. (2003) Functional and spatial segregation of secretory vesicle pools according to vesicle age. Nature. 422(6928):176-80. -PubMed