Robert Chow, MD, PhD

Retired Faculty

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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.


  • Altered adult neurogenesis and gliogenesis in patients with mesial temporal lobe epilepsy Nat Neurosci. 2022 04; 25(4):493-503. . View in PubMed
  • Global feather orientations changed by electric current iScience. 2021 Jun 25; 24(6):102671. . View in PubMed
  • Integrating Bioelectrical Currents and Ca2+ Signaling with Biochemical Signaling in Development and Pathogenesis Bioelectricity. 2020 Sep 01; 2(3):210-220. . View in PubMed
  • Robust RNA-Seq of aRNA-amplified single cell material collected by patch clamp Sci Rep. 2020 02 06; 10(1):1979. . View in PubMed
  • Focused Ultrasound Stimulates ER Localized Mechanosensitive PANNEXIN-1 to Mediate Intracellular Calcium Release in Invasive Cancer Cells Front Cell Dev Biol. 2020; 8:504. . View in PubMed
  • Stimulation strategies for selective activation of retinal ganglion cell soma and threshold reduction J Neural Eng. 2019 04; 16(2):026017. . View in PubMed
  • Mitigating Antagonism between Transcription and Proliferation Allows Near-Deterministic Cellular ReprogrammingCell Stem Cell. 2019 10 03; 25(4):486-500. e9. . View in PubMed
  • Estradiol Protects White Matter of Male C57BL6J Mice against Experimental Chronic Cerebral Hypoperfusion J Stroke Cerebrovasc Dis. 2018 Jul; 27(7):1743-1751. . View in PubMed
  • Direct measurement of bipolar cell responses to electrical stimulation in wholemount mouse retina J Neural Eng. 2018 08; 15(4):046003. . View in PubMed
  • Alveolar epithelial cell processing of nanoparticles activates autophagy and lysosomal exocytosis Am J Physiol Lung Cell Mol Physiol. 2018 08 01; 315(2):L286-L300. . View in PubMed
  • Calcium oscillations coordinate feather mesenchymal cell movement by SHH dependent modulation of gap junction networks Nat Commun. 2018 12 18; 9(1):5377. . View in PubMed
  • GCaMP expression in retinal ganglion cells characterized using a low-cost fundus imaging system J Neural Eng. 2017 10; 14(5):056018. . View in PubMed
  • The GCaMP-R Family of Genetically Encoded Ratiometric Calcium Indicators ACS Chem Biol. 2017 04 21; 12(4):1066-1074. . View in PubMed
  • Method to remove photoreceptors from whole mount retina in vitro J Neurophysiol. 2017 11 01; 118(5):2763-2769. . View in PubMed
  • Zika Virus Infects Intermediate Progenitor Cells and Post-mitotic Committed Neurons in Human Fetal Brain Tissues Sci Rep. 2017 11 01; 7(1):14883. . View in PubMed
  • Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound Front Oncol. 2017; 7:161. . View in PubMed
  • In vivo characterization of genetic expression of virus-transduced calcium indicators in retinal ganglion cells using a low-cost funduscope Annu Int Conf IEEE Eng Med Biol Soc. 2016 Aug; 2016:1316-1319. . View in PubMed
  • Calibration of Trapping Force on Cell-Size Objects From Ultrahigh-Frequency Single-Beam Acoustic Tweezer IEEE Trans Ultrason Ferroelectr Freq Control. 2016 11; 63(11):1988-1995. . View in PubMed
  • Diabetic Risk Factors Promote Islet Amyloid Polypeptide Misfolding by a Common, Membrane-mediated Mechanism Sci Rep. 2016 08 17; 6:31094. . View in PubMed
  • Assessing characteristics of RNA amplification methods for single cell RNA sequencing BMC Genomics. 2016 11 24; 17(1):966. . View in PubMed
  • Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration Sci Transl Med. 2015 Dec 16; 7(318):318ra203. . View in PubMed
  • Induced pluripotent stem cell models of Zellweger spectrum disorder show impaired peroxisome assembly and cell type-specific lipid abnormalities Stem Cell Res Ther. 2015 Aug 29; 6:158. . View in PubMed
  • Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness Sci Rep. 2015 Jun 08; 5:11207. . View in PubMed
  • 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
  • Patch clamp recordings of retinal bipolar cells in response to extracellular electrical stimulation in wholemount mouse retina Annu Int Conf IEEE Eng Med Biol Soc. 2015; 2015:3363-6. . View in PubMed
  • 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
  • Interphase gap as a means to reduce electrical stimulation thresholds for epiretinal prostheses J Neural Eng. 2014 Feb; 11(1):016007. . View in PubMed
  • 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
  • Complexin facilitates exocytosis and synchronizes vesicle release in two secretory model systems J Physiol. 2013 May 15; 591(10):2463-73. . View in PubMed
  • 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
  • Light-triggered modulation of cellular electrical activity by ruthenium diimine nanoswitches ACS Chem Neurosci. 2013 Apr 17; 4(4):585-93. . View in PubMed
  • 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
  • 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
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  • 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
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  • 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
  • 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
  • Ezrin mediates tethering of the gamma-aminobutyric acid transporter GAT1 to actin filaments via a C-terminal PDZ-interacting domain Biophys J. 2009 Apr 08; 96(7):2949-60. . View in PubMed
  • 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
  • Complexin II plays a positive role in Ca2+-triggered exocytosis by facilitating vesicle priming Proc Natl Acad Sci U S A. 2008 Dec 09; 105(49):19538-43. . View in PubMed
  • A novel tool to visualize the cell secretory pathwayFocus 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
  • 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
  • Human insulin vesicle dynamics during pulsatile secretion Diabetes. 2007 May; 56(5):1277-88. . View in PubMed
  • 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
  • Mouse adrenal chromaffin cell isolation J Vis Exp. 2007 Jan 05; (2):129. . View in PubMed
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  • Nanobiolistic delivery of indicators to the living mouse retina J Neurosci Methods. 2006 May 15; 153(1):154-61. . View in PubMed
  • Pancreatic beta-cells secrete insulin in fast- and slow-release forms Diabetes. 2006 Mar; 55(3):600-7. . View in PubMed
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  • Real-time imaging of renin release in vitro Am J Physiol Renal Physiol. 2004 Aug; 287(2):F329-35. . View in PubMed
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  • Cylindrically etched carbon-fiber microelectrodes for low-noise amperometric recording of cellular secretion Anal Chem. 1998 Mar 01; 70(5):985-90. . View in PubMed
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