Faculty

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Robert Hsiu-Ping Chow, MD, PhD
Professor of Physiology & Biophysics
Zilkha Neurogenetic Institute
ZNI 323 1501 San Pablo Street Health Sciences Campus Los Angeles
+1 323 442 2901

Overview

The aim of my laboratory is to advance our understanding of how hormone and neuronal secretion is controlled in normal and pathological states, and then to translate this knowledge to improve human health. 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.

We work with neurons and endocrine cells. Many endocrine cells such as pancreatic beta and chromaffin 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. Ralf Langen (Biochemistry, ZNI), we are studying the mechanism of cell death in 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.

In collaboration with Mark Humayun (Ophthalmology, BME) and Jim Weiland (Ophthalmology, BME), we are studying methods to restore sight to the blind. In my laboratory, we perform imaging of retinal ganglion and bipolar neurons expressing genetically encoded calcium indicators, in order to better understand how to improve signaling between the microelectrode array of an implanted epiretinal prosthesis and the retina. In addition, we are working on photoactivated molecules that embed in cell membranes, converting the cells into light-sensors -- a novel cellular prosthesis.

A recent interest of our laboratory pertains to cancer biology. When cancer cells become invasive, they express many neuronal-type proteins, including those involved in electrical signaling, secretion, and motility. Thus, we have been studying how these genes are turned on, in an effort to develop approaches to recognize the potential of cancer cells to invade/metastasize, as well as to find ways to stop invasion. One recent discovery we made in collaboration with Prof. Kirk Shung (BME) is that highly invasive breast cancer cells, but not less invasive cells, exhibit calcium elevations upon ultrasound stimulation. We are investigating the pathways involved, and we are collaborating with oncologists to develop a possible clinical assay.

Publications

Okada AK, Teranishi K, Isas JM, Bedrood S, Chow RH, Langen R. Diabetic Risk Factors Promote Islet Amyloid Polypeptide Misfolding by a Common, Membrane-mediated Mechanism. Sci Rep. 2016; 6:31094. View in: PubMed

Weitz AC, Nanduri D, Behrend MR, Gonzalez-Calle A, Greenberg RJ, Humayun MS, Chow RH, Weiland JD. Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration. Sci Transl Med. 2015 Dec 16; 7(318):318ra203. View in: PubMed

Walston ST, Chow RH, Weiland JD. Patch clamp recordings of retinal bipolar cells in response to extracellular electrical stimulation in wholemount mouse retina. Conf Proc IEEE Eng Med Biol Soc. 2015 Aug; 2015:3363-6. View in: PubMed

Woolcott OO, Richey JM, Kabir M, Chow RH, Iyer MS, Kirkman EL, Stefanovski D, Lottati M, Kim SP, Harrison LN, Ionut V, Zheng D, Hsu IR, Catalano KJ, Chiu JD, Bradshaw H, Wu Q, Kolka CM, Bergman RN. Corrections: High-Fat Diet-Induced Insulin Resistance does not Increase Plasma Anandamide Levels or Potentiate Anandamide Insulinotropic Effect in Isolated Canine Islets. PLoS One. 2015; 10(6):e0131033. View in: PubMed

Wang XM, Yik WY, Zhang P, Lu W, Huang N, Kim BR, Shibata D, Zitting M, Chow RH, Moser AB, Steinberg SJ, Hacia JG. Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities. Stem Cell Res Ther. 2015; 6(1):158. View in: PubMed

Woolcott OO, Richey JM, Kabir M, Chow RH, Iyer MS, Kirkman EL, Stefanovski D, Lottati M, Kim SP, Harrison LN, Ionut V, Zheng D, Hsu IR, Catalano KJ, Chiu JD, Bradshaw H, Wu Q, Bergman RN. High-fat diet-induced insulin resistance does not increase plasma anandamide levels or potentiate anandamide insulinotropic effect in isolated canine islets. PLoS One. 2015; 10(4):e0123558. View in: PubMed

Sook Lee N, Evgrafov OV, Souaiaia T, Bonyad A, Herstein J, Yeun Lee J, Kim J, Ning Y, Sixto M, Weitz AC, Lenz HJ, Wang K, Knowles JA, Press MF, Salvaterra PM, Kirk Shung K, Chow RH. Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness. Sci Rep. 2015; 5:11207. View in: PubMed

Weitz AC, Behrend MR, Ahuja AK, Christopher P, Wei J, Wuyyuru V, Patel U, Greenberg RJ, Humayun MS, Chow RH, Weiland JD. Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses. J Neural Eng. 2014 Feb; 11(1):016007. View in: PubMed

Hwang JY, Lee NS, Lee C, Lam KH, Kim HH, Woo J, Lin MY, Kisler K, Choi H, Zhou Q, Chow RH, Shung KK. Investigating contactless high frequency ultrasound microbeam stimulation for determination of invasion potential of breast cancer cells. Biotechnol Bioeng. 2013 Oct; 110(10):2697-705. View in: PubMed

Lin MY, Rohan JG, Cai H, Reim K, Ko CP, Chow RH. Complexin facilitates exocytosis and synchronizes vesicle release in two secretory model systems. J Physiol. 2013 May 15; 591(Pt 10):2463-73. View in: PubMed

Kisler K, Chow RH, Dominguez R. Fluorescently-Labeled Estradiol Internalization and Membrane Trafficking in Live N-38 Neuronal Cells Visualized with Total Internal Reflection Fluorescence Microscopy. J Steroids Horm Sci. 2013 Apr 20; Suppl 12. View in: PubMed

Rohan JG, Citron YR, Durrell AC, Cheruzel LE, Gray HB, Grubbs RH, Humayun M, Engisch KL, Pikov V, Chow RH. Light-triggered modulation of cellular electrical activity by ruthenium diimine nanoswitches. ACS Chem Neurosci. 2013 Apr 17; 4(4):585-93. View in: PubMed

Weitz AC, Behrend MR, Lee NS, Klein RL, Chiodo VA, Hauswirth WW, Humayun MS, Weiland JD, Chow RH. Imaging the response of the retina to electrical stimulation with genetically encoded calcium indicators. J Neurophysiol. 2013 Apr; 109(7):1979-88. View in: PubMed

Lee NS, Rohan JG, Zitting M, Kamath S, Weitz A, Sipos A, Salvaterra PM, Hasegawa K, Pera M, Chow RH. A novel dual-color reporter for identifying insulin-producing Beta- cells and classifying heterogeneity of insulinoma cell lines. PLoS One. 2012; 7(4):e35521. View in: PubMed

Woolcott OO, Bergman RN, Richey JM, Kirkman EL, Harrison LN, Ionut V, Lottati M, Zheng D, Hsu IR, Stefanovski D, Kabir M, Kim SP, Catalano KJ, Chiu JD, Chow RH. Simplified method to isolate highly pure canine pancreatic islets. Pancreas. 2012 Jan; 41(1):31-8. View in: PubMed

Behrend MR, Ahuja AK, Humayun MS, Chow RH, Weiland JD. Resolution of the epiretinal prosthesis is not limited by electrode size. IEEE Trans Neural Syst Rehabil Eng. 2011 Aug; 19(4):436-42. View in: PubMed

Ye R, Ni M, Wang M, Luo S, Zhu G, Chow RH, Lee AS. Inositol 1,4,5-trisphosphate receptor 1 mutation perturbs glucose homeostasis and enhances susceptibility to diet-induced diabetes. J Endocrinol. 2011 Aug; 210(2):209-17. View in: PubMed

Weitz AC, Behrend MR, Humayun MS, Chow RH, Weiland JD. Interphase gap decreases electrical stimulation threshold of retinal ganglion cells. Conf Proc IEEE Eng Med Biol Soc. 2011 Aug; 2011:6725-8. View in: PubMed

Crawford CA, Akopian G, Ring J, Jakowec MW, Petzinger GM, Andersen JK, Vittozzi-Wong P, Wang K, Farley CM, Charntikov S, Mitroi D, Beal MF, Chow R, Walsh JP. Acute and long-term response of dopamine nigrostriatal synapses to a single, low-dose episode of 3-nitropropionic acid-mediated chemical hypoxia. Synapse. 2011 Apr; 65(4):339-50. View in: PubMed

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

McDonald ML, Wang Y, Selvam S, Nakamura T, Chow RH, Schechter JE, Yiu SC, Mircheff AK. Cytopathology and exocrine dysfunction induced in ex vivo rabbit lacrimal gland acinar cell models by chronic exposure to histamine or serotonin. Invest Ophthalmol Vis Sci. 2009 Jul; 50(7):3164-75. View in: PubMed

Behrend MR, Ahuja AK, Humayun MS, Weiland JD, Chow RH. Selective labeling of retinal ganglion cells with calcium indicators by retrograde loading in vitro. J Neurosci Methods. 2009 May 15; 179(2):166-72. View in: PubMed

Imoukhuede PI, Moss FJ, Michael DJ, Chow RH, Lester HA. Ezrin mediates tethering of the gamma-aminobutyric acid transporter GAT1 to actin filaments via a C-terminal PDZ-interacting domain. Biophys J. 2009 Apr 8; 96(7):2949-60. View in: PubMed

Michael DJ, Tapechum S, Rohan JG, Johnson JM, Chow RH. Fluorescent cargo proteins in peptidergic endocrine cells: cell type determines secretion kinetics at exocytosis. Ann N Y Acad Sci. 2009 Jan; 1152:7-17. View in: PubMed

Cai H, Reim K, Varoqueaux F, Tapechum S, Hill K, Sørensen JB, Brose N, Chow RH. Complexin II plays a positive role in Ca2+-triggered exocytosis by facilitating vesicle priming. Proc Natl Acad Sci U S A. 2008 Dec 9; 105(49):19538-43. View in: PubMed

Peti-Peterdi J, Chow RH. A novel tool to visualize the cell secretory pathway. Focus on "a fluorimetry-based ssYFP secretion assay to monitor vasopressin-induced exocytosis in LLC-PK1 cells expressing aquaporin-2". Am J Physiol Cell Physiol. 2008 Dec; 295(6):C1473. View in: PubMed

Akopian G, Crawford C, Beal MF, Cappelletti M, Jakowec MW, Petzinger GM, Zheng L, Gheorghe SL, Reichel CM, Chow R, Walsh JP. Decreased striatal dopamine release underlies increased expression of long-term synaptic potentiation at corticostriatal synapses 24 h after 3-nitropropionic-acid-induced chemical hypoxia. J Neurosci. 2008 Sep 17; 28(38):9585-97. View in: PubMed

Michael DJ, Xiong W, Geng X, Drain P, Chow RH. Human insulin vesicle dynamics during pulsatile secretion. Diabetes. 2007 May; 56(5):1277-88. View in: PubMed

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):1262-75. View in: PubMed

Kolski-Andreaco A, Cai H, Currle DS, Chandy KG, Chow RH. Mouse adrenal chromaffin cell isolation. J Vis Exp. 2007; (2):129. View in: 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. View in: 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. View in: 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. View in: 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. View in: 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. View in: 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. View in: 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. View in: 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. View in: PubMed

Duncan RR, Greaves J, Wiegand UK, Matskevich I, Bodammer G, Apps DK, Shipston MJ, Chow RH. Functional and spatial segregation of secretory vesicle pools according to vesicle age. Nature. 2003 Mar 13; 422(6928):176-80. View in: PubMed

Chan SA, Chow R, Smith C. Calcium dependence of action potential-induced endocytosis in chromaffin cells. Pflugers Arch. 2003 Feb; 445(5):540-6. View in: PubMed

Wiegand UK, Don-Wauchope A, Matskevich I, Duncan RR, Greaves J, Shipston MJ, Apps DK, Chow RH. Exocytosis studies in a chromaffin cell-free system: imaging of single-vesicle exocytosis in a chromaffin cell-free system using total internal reflection fluorescence microscopy. Ann N Y Acad Sci. 2002 Oct; 971:257-61. View in: PubMed

Duncan RR, Greaves J, Tapechum S, Apps DK, Shipston MJ, Chow RH. Efficacy of Semliki Forest virus transduction of bovine adrenal chromaffin cells: an analysis of heterologous protein targeting and distribution. Ann N Y Acad Sci. 2002 Oct; 971:641-6. View in: PubMed

Greaves J, Duncan RR, Tapechum S, Apps DK, Shipston MJ, Chow RH. Use of ANF-EGFP for the visualization of secretory vesicles in bovine adrenal chromaffin cells. Ann N Y Acad Sci. 2002 Oct; 971:275-6. View in: PubMed

Voets T, Moser T, Lund PE, Chow RH, Geppert M, Südhof TC, Neher E. Intracellular calcium dependence of large dense-core vesicle exocytosis in the absence of synaptotagmin I. Proc Natl Acad Sci U S A. 2001 Sep 25; 98(20):11680-5. View in: PubMed

Duncan RR, Apps DK, Learmonth MP, Shipston MJ, Chow RH. Is double C2 protein (DOC2) expressed in bovine adrenal medulla? A commercial anti-DOC2 monoclonal antibody recognizes a major bovine mitochondrial antigen. Biochem J. 2000 Oct 1; 351(Pt 1):33-7. View in: PubMed

Duncan RR, Shipston MJ, Chow RH. Double C2 protein. A review. Biochimie. 2000 May; 82(5):421-6. View in: PubMed

Duncan RR, Betz A, Shipston MJ, Brose N, Chow RH. Transient, phorbol ester-induced DOC2-Munc13 interactions in vivo. J Biol Chem. 1999 Sep 24; 274(39):27347-50. View in: PubMed

Duncan RR, Don-Wauchope AC, Tapechum S, Shipston MJ, Chow RH, Estibeiro P. High-efficiency Semliki Forest virus-mediated transduction in bovine adrenal chromaffin cells. Biochem J. 1999 Sep 15; 342 Pt 3:497-501. View in: PubMed

Oheim M, Loerke D, Chow RH, Stühmer W. Evanescent-wave microscopy: a new tool to gain insight into the control of transmitter release. Philos Trans R Soc Lond B Biol Sci. 1999 Feb 28; 354(1381):307-18. View in: PubMed

Oheim M, Loerke D, Stühmer W, Chow RH. Multiple stimulation-dependent processes regulate the size of the releasable pool of vesicles. Eur Biophys J. 1999; 28(2):91-101. View in: PubMed

Jaffe EH, Marty A, Schulte A, Chow RH. Extrasynaptic vesicular transmitter release from the somata of substantia nigra neurons in rat midbrain slices. J Neurosci. 1998 May 15; 18(10):3548-53. View in: PubMed

Haller M, Heinemann C, Chow RH, Heidelberger R, Neher E. Comparison of secretory responses as measured by membrane capacitance and by amperometry. Biophys J. 1998 Apr; 74(4):2100-13. View in: PubMed

Schulte A, Chow RH. Cylindrically etched carbon-fiber microelectrodes for low-noise amperometric recording of cellular secretion. Anal Chem. 1998 Mar 1; 70(5):985-90. View in: PubMed

Oheim M, Loerke D, Stühmer W, Chow RH. The last few milliseconds in the life of a secretory granule. Docking, dynamics and fusion visualized by total internal reflection fluorescence microscopy (TIRFM). Eur Biophys J. 1998; 27(2):83-98. View in: PubMed

Gillis KD, Chow RH. Kinetics of exocytosis in adrenal chromaffin cells. Semin Cell Dev Biol. 1997 Apr; 8(2):133-40. View in: PubMed

Schulte A, Chow RH. A simple method for insulating carbon-fiber microelectrodes using anodic electrophoretic deposition of paint. Anal Chem. 1996 Sep 1; 68(17):3054-8. View in: PubMed

Zhou Z, Misler S, Chow RH. Rapid fluctuations in transmitter release from single vesicles in bovine adrenal chromaffin cells. Biophys J. 1996 Mar; 70(3):1543-52. View in: PubMed

Chow RH, Klingauf J, Heinemann C, Zucker RS, Neher E. Mechanisms determining the time course of secretion in neuroendocrine cells. Neuron. 1996 Feb; 16(2):369-76. View in: PubMed

Moser T, Chow RH, Neher E. Swelling-induced catecholamine secretion recorded from single chromaffin cells. Pflugers Arch. 1995 Dec; 431(2):196-203. View in: PubMed

Chow RH, Lund PE, Löser S, Panten U, Gylfe E. Coincidence of early glucose-induced depolarization with lowering of cytoplasmic Ca2+ in mouse pancreatic beta-cells. J Physiol. 1995 Jun 15; 485 ( Pt 3):607-17. View in: PubMed

Chow RH, Klingauf J, Neher E. Time course of Ca2+ concentration triggering exocytosis in neuroendocrine cells. Proc Natl Acad Sci U S A. 1994 Dec 20; 91(26):12765-9. View in: PubMed

Heinemann C, Chow RH, Neher E, Zucker RS. Kinetics of the secretory response in bovine chromaffin cells following flash photolysis of caged Ca2+. Biophys J. 1994 Dec; 67(6):2546-57. View in: PubMed

Heinemann C, von Rüden L, Chow RH, Neher E. A two-step model of secretion control in neuroendocrine cells. Pflugers Arch. 1993 Jul; 424(2):105-12. View in: PubMed

Chow RH, von Rüden L, Neher E. Delay in vesicle fusion revealed by electrochemical monitoring of single secretory events in adrenal chromaffin cells. Nature. 1992 Mar 5; 356(6364):60-3. View in: PubMed

Chow RH. Cadmium block of squid calcium currents. Macroscopic data and a kinetic model. J Gen Physiol. 1991 Oct; 98(4):751-70. View in: PubMed

Parsons TD, Chow RH. Neuritic outgrowth in primary cell culture of neurons from the squid, Loligo pealei. Neurosci Lett. 1989 Feb 13; 97(1-2):23-8. View in: PubMed

Armstrong CM, Chow RH. Supercharging: a method for improving patch-clamp performance. Biophys J. 1987 Jul; 52(1):133-6. View in: PubMed

Fakunding JL, Chow R, Catt KJ. The role of calcium in the stimulation of aldosterone production by adrenocorticotropin, angiotensin II, and potassium in isolated glomerulosa cells. Endocrinology. 1979 Aug; 105(2):327-33. View in: PubMed

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