Education:
BA 1981 Biology- Brown University, Providence, RI
MD-PhD 1988 Physiology- University of Pennsylvania, Philadelphia, PA
Postdoctoral Research Fellowship:
1990-1995 Max Planck Institute, Gottingen, Germany
Started at USC: 2000
Research Topics: Cellular Neurobiology, Diabetes/Metabolic Diseases, Neurogenetics, Physiology
Research Description
The aim of the Chow laboratory is to advance our understanding of how hormone and neuronal secretion (exocytosis) is controlled in normal and pathological states. In the last two decades, the molecular biology revolution has led to the cloning of dozens of synaptic and endocrine proteins. 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.
We work with adrenal chromaffin cells and pancreatic beta cells. Both are endocrine cells that, 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 having secretory vesicles that are larger than synaptic vesicles. The large size enables exocytosis to be studied readily with imaging and electrophysiological approaches. We work with transgenic mice in which proteins have been selectively knocked out, or 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).
An important focus of the laboratory is the cellular mechanism of abnormal secretion and cell death in diabetes mellitus. In collaboration with Prof. Richard Bergman at USC, 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
Pyrko P, Kardosh A, Liu YT, Soriano N, Xiong W, Chow RH, Uddin J, Petasis NA, Mircheff AK, Farley RA, Louie SG, Chen TC, Schönthal AH. - Calcium-activated endoplasmic reticulum stress as a major component of tumor cell death induced by 2,5-dimethyl-celecoxib, a non-coxib analogue of celecoxib. - Mol Cancer Ther [ 2007 ] Apr;6(4):1262-1275 . PubMed
Michael DJ, Xiong W, Geng X, Drain P, Chow RH. - Human Insulin Vesicle Dynamics During Pulsatile Secretion. - Diabetes [ 2007 ] Feb 22; . PubMed
Michael DJ, Cai H, Xiong W, Ouyang J, Chow RH. - Mechanisms of peptide hormone secretion. - Trends Endocrinol Metab [ 2006 ] Dec;17(10):408-15 . PubMed
Oheim M, Michael DJ, Geisbauer M, Madsen D, Chow RH. - Principles of two-photon excitation fluorescence microscopy and other nonlinear imaging approaches. - Adv Drug Deliv Rev [ 2006 ] Sep 15;58(7):788-808 . PubMed
Michael DJ, Ritzel RA, Haataja L, Chow RH. - Pancreatic beta-cells secrete insulin in fast- and slow-release forms. - Diabetes [ 2006 ] Mar;55(3):600-7 . PubMed
Roizenblatt R, Weiland JD, Carcieri S, Qiu G, Behrend M, Humayun MS, Chow RH. - Nanobiolistic delivery of indicators to the living mouse retina. - J Neurosci Methods [ 2006 ] May 15;153(1):154-61 . PubMed
Michael DJ, Geng X, Cawley NX, Loh YP, Rhodes CJ, Drain P, Chow RH. - Fluorescent cargo proteins in pancreatic beta-cells: design determines secretion kinetics at exocytosis. - Biophys J [ 2004 ] Dec;87(6):L03-5 . PubMed
Peti-Peterdi J, Fintha A, Fuson AL, Tousson A, Chow RH. - Real-time imaging of renin release in vitro. - Am J Physiol Renal Physiol [ 2004 ] Aug;287(2):F329-35 . PubMed
Qian L, Wang Y, Xie J, Rose CM, Yang T, Nakamura T, Sandberg M, Zeng H, Schechter JE, Chow RH, Hamm-Alvarez SF, Mircheff AK. - Biochemical changes contributing to functional quiescence in lacrimal gland acinar cells after chronic ex vivo exposure to a muscarinic agonist. - Scand J Immunol [ 2003 ] Nov;58(5):550-65 . PubMed
Wiegand UK, Duncan RR, Greaves J, Chow RH, Shipston MJ, Apps DK. - Red, yellow, green go!--A novel tool for microscopic segregation of secretory vesicle pools according to their age. - Biochem Soc Trans [ 2003 ] Aug;31(Pt 4):851-6 . PubMed
