Positions

Research Areas research areas

Overview

  • My research focuses on the regulation of the visual signaling pathway in photoreceptor cells, with emphasis on the structure, function, and regulation of the photoreceptor phosphodiesterase (PDE6). My lab group consists of a research scientist, graduate students, and undergraduate student researchers. I have broad training in the field of biochemistry and molecular biology, with specific expertise in enzymology, protein chemistry, and molecular pharmacology. In addition to my longstanding contributions to understanding cyclic nucleotide signaling pathways in photoreceptor cells, our work is also contributing to efforts to identify therapeutic interventions for retinal degenerative diseases. In addition, our lab investigates the physiological roles of phosphodiesterases in the nematode C. elegans, with applications to developing chemical controls for parasitic nematodes.
    I have designed and taught general and upper-level biochemistry lecture and laboratory courses to undergraduate students, as well as offering graduate courses in cell signaling.
    My service contributions include serving as academic administrator of the Molecular, Cellular and Biomedical Sciences Department at UNH. More recently, I have served as Principal Investigator of the COBRE: Center of Integrated Biomedical and Bioengineering Research which includes mentoring early career stage faculty and promoting biomedical research infrastructure at UNH. I was awarded the University Distinguished Professor award in 2016 in recognition of my contributions to teaching, research, academic administration, and service.

    • Selected Publications

    Academic Article

    Year Title
    2023 Coupling of conformational dynamics and inhibitor binding in the phosphodiesterase-5 family..  Protein Science.  32:e4720. 2023
    2022 Reconstitution of Membrane-associated Components of a G-protein Signaling Pathway on Membrane-coated Nanoparticles (Lipobeads)..  Bio Protoc.  12:e4303. 2022
    2022 Photoreceptor Phosphodiesterase (PDE6): Structure, Regulatory Mechanisms, and Implications for Treatment of Retinal Diseases..  Advances in Experimental Medicine and Biology.  1371:33-59. 2022
    2021 Photoreceptor phosphodiesterase (PDE6): activation and inactivation mechanisms during visual transduction in rods and cones..  Pfluegers Archiv: European journal of physiology.  473:1377-1391. 2021
    2020 Structural Analysis of the Regulatory GAF Domains of cGMP Phosphodiesterase Elucidates the Allosteric Communication Pathway..  Journal of Molecular Biology.  432:5765-5783. 2020
    2019 The molecular architecture of photoreceptor phosphodiesterase 6 (PDE6) with activated G protein elucidates the mechanism of visual excitation..  Journal of Biological Chemistry.  294:19486-19497. 2019
    2019 Allosteric Regulation of Rod Photoreceptor Phosphodiesterase 6 (PDE6) Elucidated by Chemical Cross-Linking and Quantitative Mass Spectrometry..  Journal of Molecular Biology.  431:3677-3689. 2019
    2019 The N termini of the inhibitory γ-subunits of phosphodiesterase-6 (PDE6) from rod and cone photoreceptors differentially regulate transducin-mediated PDE6 activation..  Journal of Biological Chemistry.  294:8351-8360. 2019
    2019 Pharmacological and molecular dynamics analyses of differences in inhibitor binding to human and nematode PDE4: Implications for management of parasitic nematodes..  PLoS ONE.  14:e0214554. 2019
    2014 Molecular architecture of photoreceptor phosphodiesterase elucidated by chemical cross-linking and integrative modeling..  Journal of Molecular Biology.  426:3713-3728. 2014
    2012 Identification of amino acid residues responsible for the selectivity of tadalafil binding to two closely related phosphodiesterases, PDE5 and PDE6..  Journal of Biological Chemistry.  287:41406-41416. 2012
    2012 Functional mapping of interacting regions of the photoreceptor phosphodiesterase (PDE6) γ-subunit with PDE6 catalytic dimer, transducin, and regulator of G-protein signaling9-1 (RGS9-1)..  Journal of Biological Chemistry.  287:26312-26320. 2012
    2012 Characterization of conformational changes and protein-protein interactions of rod photoreceptor phosphodiesterase (PDE6)..  Journal of Biological Chemistry.  287:20111-20121. 2012
    2011 Phosphodiesterase 6C, cGMP-specific cone alpha'..  AFCS Nat Mol Pages.  2011:A001756. 2011
    2011 Phosphodiesterase 6D, cGMP-specific rod delta..  AFCS Nat Mol Pages.  2011:A001757. 2011
    2011 Phosphodiesterase 6H, cone-specific inhibitor: Basis Sequence: Mouse..  AFCS Nat Mol Pages.  2011:A001758. 2011
    2010 Structural requirements of the photoreceptor phosphodiesterase gamma-subunit for inhibition of rod PDE6 holoenzyme and for its activation by transducin..  Journal of Biological Chemistry.  285:4455-4463. 2010
    2009 Probing the catalytic sites and activation mechanism of photoreceptor phosphodiesterase using radiolabeled phosphodiesterase inhibitors..  Journal of Biological Chemistry.  284:31541-31547. 2009
    2008 Direct allosteric regulation between the GAF domain and catalytic domain of photoreceptor phosphodiesterase PDE6..  Journal of Biological Chemistry.  283:29699-29705. 2008
    2006 The glutamic acid-rich protein-2 (GARP2) is a high affinity rod photoreceptor phosphodiesterase (PDE6)-binding protein that modulates its catalytic properties..  Journal of Biological Chemistry.  281:5500-5505. 2006
    2005 Efficacy and selectivity of phosphodiesterase-targeted drugs in inhibiting photoreceptor phosphodiesterase (PDE6) in retinal photoreceptors..  Investigative Ophthalmology and Visual Science.  46:3060-3066. 2005
    2005 Rod and cone opsin families differ in spectral tuning domains but not signal transducing domains as judged by saturated evolutionary trace analysis..  Journal of Molecular Evolution.  61:75-89. 2005
    2005 cGMP signaling in vertebrate retinal photoreceptor cells..  Frontiers in Bioscience.  10:1191-1204. 2005
    2005 Evaluation of the 17-kDa prenyl-binding protein as a regulatory protein for phototransduction in retinal photoreceptors..  Journal of Biological Chemistry.  280:1248-1256. 2005
    2005 Assay and functional properties of PrBP(PDEdelta), a prenyl-binding protein interacting with multiple partners..  Methods in Enzymology.  403:42-56. 2005
    2005 Cyclic guanosine 5'-monophosphate binding to regulatory GAF domains of photoreceptor phosphodiesterase..  Methods in Molecular Biology.  307:141-154. 2005
    2005 Purification of PDE6 isozymes from mammalian retina..  Methods in Molecular Biology.  307:125-140. 2005
    2004 Characteristics of photoreceptor PDE (PDE6): similarities and differences to PDE5..  International Journal of Impotence Research.  16 Suppl 1:S28-S33. 2004
    2003 Relative potency of various classes of phosphodiesterase (PDE) inhibitors for rod and cone photoreceptor PDE.  Investigative Ophthalmology and Visual Science.  44:U357-U357. 2003
    2002 Regulation of cone photoreceptor phosphodiesterase (PDE6C) by its inhibitory gamma ' subunit and by cGMP binding.  Investigative Ophthalmology and Visual Science.  43:U451-U451. 2002
    2002 Regulation of photoreceptor phosphodiesterase (PDE6) by phosphorylation of its inhibitory gamma subunit re-evaluated..  Journal of Biological Chemistry.  277:5017-5023. 2002
    2001 Molecular organization of bovine rod cGMP-phosphodiesterase 6..  Journal of Molecular Biology.  310:781-791. 2001
    2001 The catalytic and GAF domains of the rod cGMP phosphodiesterase (PDE6) heterodimer are regulated by distinct regions of its inhibitory gamma subunit..  Journal of Biological Chemistry.  276:27527-27534. 2001
    2000 Mechanism of transducin activation of frog rod photoreceptor phosphodiesterase. Allosteric interactiona between the inhibitory gamma subunit and the noncatalytic cGMP-binding sites..  Journal of Biological Chemistry.  275:38611-38619. 2000
    2000 Identifying domains on the inhibitory gamma subunit (P gamma) that regulate bovine rod photoreceptor phosphodiesterase (PDE) function..  Investigative Ophthalmology and Visual Science.  41:S606-S606. 2000
    2000 Subcellular localization of frog rod photoreceptor phosphodiesterase (PDE) subunits..  Investigative Ophthalmology and Visual Science.  41:S606-S606. 2000
    2000 Kinetics and regulation of cGMP binding to noncatalytic binding sites on photoreceptor phosphodiesterase..  Methods in Enzymology.  315:646-672. 2000
    1999 cGMP binding to noncatalytic sites on mammalian rod photoreceptor phosphodiesterase is regulated by binding of its gamma and delta subunits..  Journal of Biological Chemistry.  274:18813-18820. 1999
    1999 Regulation of photoreceptor phosphodiesterase catalysis by its non-catalytic cGMP-binding sites..  Biochemical Journal.  340 ( Pt 3):863-869. 1999
    1999 Potency and mechanism of action of E4021, a type 5 phosphodiesterase isozyme-selective inhibitor, on the photoreceptor phosphodiesterase depend on the state of activation of the enzyme..  Molecular Pharmacology.  55:508-514. 1999
    1998 Structural features of the noncatalytic cGMP binding sites of frog photoreceptor phosphodiesterase using cGMP analogs..  Journal of Biological Chemistry.  273:5557-5565. 1998
    1998 Photoreceptor phosphodiesterase: interaction of inhibitory gamma subunit and cyclic GMP with specific binding sites on catalytic subunits..  Methods.  14:93-104. 1998
    1994 cGMP binding sites on photoreceptor phosphodiesterase: role in feedback regulation of visual transduction..  Proceedings of the National Academy of Sciences of USA.  91:4845-4849. 1994
    1994 Regulation of intracellular cyclic GMP concentration by light and calcium in electropermeabilized rod photoreceptors..  Journal of General Physiology.  103:67-86. 1994
    1993 A centrifugal separation procedure detects moderate affinity cGMP binding sites in membrane-associated proteins and permeabilized cells..  Analytical Biochemistry.  215:159-161. 1993
    1993 Intracellular cGMP concentration in rod photoreceptors is regulated by binding to high and moderate affinity cGMP binding sites..  Journal of Biological Chemistry.  268:17190-17198. 1993
    1992 NUCLEOTIDE ENERGY-METABOLISM IN ELECTROPERMEABILIZED ROD PHOTORECEPTORS.  Investigative Ophthalmology and Visual Science.  33:1008-1008. 1992
    1992 LIGHT-INDUCED-CHANGES IN CGMP METABOLISM IN ELECTROPORATED RETINAL RODS.  The FASEB Journal.  6:A519-A519. 1992
    1992 Mechanisms of amplification, deactivation, and noise reduction in invertebrate photoreceptors..  Society of General Physiologists Series.  47:175-199. 1992
    1989 Cyclic GMP levels and membrane current during onset, recovery, and light adaptation of the photoresponse of detached frog photoreceptors..  Journal of Biological Chemistry.  264:15384-15391. 1989
    1989 Characterization of guanylate cyclase in squid photoreceptors..  Visual Neuroscience.  3:1-7. 1989
    1986 CHANGES IN CGMP CONCENTRATION CORRELATE WITH SOME, BUT NOT ALL, ASPECTS OF THE LIGHT-REGULATED CONDUCTANCE OF FROG ROD PHOTORECEPTORS.  Journal of Biological Chemistry.  261:2965-2975. 1986
    1986 Changes in cGMP concentration correlate with some, but not all, aspects of the light-regulated conductance of frog rod photoreceptors..  Journal of Biological Chemistry.  261:12965-12975. 1986
    1986 cGMP influences guanine nucleotide binding to frog photoreceptor G-protein..  Journal of Biological Chemistry.  261:313-318. 1986
    1984 Light-induced decreases in cGMP concentration precede changes in membrane permeability in frog rod photoreceptors..  Journal of Biological Chemistry.  259:9635-9641. 1984
    1981 Formulation of the general rate equation for subunit flux at steady-state..  Journal of Molecular Biology.  150:599-602. 1981
    1981 Head-to-tail polymerization of microtubules in vitro..  Journal of Molecular Biology.  150:577-599. 1981
    1977 Release of Escherichia coli DNA from membrane complexes by single-strand endonucleases..  Proceedings of the National Academy of Sciences of USA.  74:2756-2760. 1977
    1974 Isolation and characterization of rifampin-resistant and streptolydigin-resistant mutants of Bacillus subtilis with altered sporulation properties..  Journal of Bacteriology.  120:253-265. 1974

    Chapter

    Year Title
    2010 Chapter 177 Function and Regulation of Photoreceptor Phosphodiesterase (PDE6) in the Visual Signaling Pathway.  1445-1451. 2010
    2010 Chapter 178 Regulation of Cyclic Nucleotide Levels by Sequestration.  1453-1459. 2010
    2010 Function and Regulation of Photoreceptor Phosphodiesterase (PDE6) in the Visual Signaling Pathway.  1445-1451. 2010
    2010 Regulation of Cyclic Nucleotide Levels by Sequestration.  1453-1459. 2010
    2005 Purification of PDE6 Isozymes From Mammalian Retina.  125-140. 2005

    Conference Paper

    Year Title
    2016 NEMATODE PHOSPHODIESTERASES ARE PROMISING TARGETS FOR NOVEL NEMATICIDES.  Journal of Nematology. 368-369. 2016
    2014 Characterization of retinal phosphodiesterase: Dependence of activity on zinc and cadmium concentration.  ACS National Meeting Book of Abstracts. 2014
    2005 Drugs targeting specific phosphodiesterase families: Selectivity toward photoreceptor PDE6 and effects on intact photoreceptors.  Investigative Ophthalmology and Visual Science. 2005
    2003 Characterization of rod photoreceptor Glutamic Acid Rich Protein interaction with rod photoreceptor PDE6.  Investigative Ophthalmology and Visual Science. U135-U135. 2003
    2002 Regulation of rod photoreceptor phosphodiesterase (PDE6) by phosphorylation of its catalytic subunits.  Investigative Ophthalmology and Visual Science. U318-U318. 2002
    2001 Characterization of the membrane-associated photoreceptor phosphodiesterase (PDE) following detergent solubilization from rod outer segment membranes..  Investigative Ophthalmology and Visual Science. S186-S186. 2001
    2001 Effect of phosphorylation of the inhibitory gamma subunit (P gamma) on cGMP binding and catalytic activity of bovine rod photoreceptor phosphodiesterase (PDE).  Investigative Ophthalmology and Visual Science. S186-S186. 2001
    2001 Multiple sites of high affinity interaction of the inhibitory gamma subunit (P gamma) with rod photoreceptor phosphodiesterase (PDE6)..  Investigative Ophthalmology and Visual Science. S186-S186. 2001
    2001 Solubilization of membrane-associated frog phosphodiesterase (PDE) in vitro by the frog homologue of the bovine 17 kDa delta protein..  Investigative Ophthalmology and Visual Science. S187-S187. 2001
    2000 Transducin activation of photoreceptor phosphodiesterase: effects on catalytic activity, cGMP binding affinity to the noncatalytic sites, and PDE gamma subunit dissociation from the catalytic alpha beta dimer..  Investigative Ophthalmology and Visual Science. S606-S606. 2000
    1997 Regulation of the binding affinity and rate of dissociation of cGMP at noncatalytic binding sites on photoreceptor phosphodiesterase.  Investigative Ophthalmology and Visual Science. 103-103. 1997
    1997 The PDE inhibitor E4021 has complex effects on the frog rod photoreceptor phosphodiesterase.  Investigative Ophthalmology and Visual Science. 98-98. 1997
    1995 KINETICS OF CGMP BINDING TO NONCATALYTIC BINDING-SITES ON FROG ROD PHOTORECEPTOR PHOSPHODIESTERASE.  Investigative Ophthalmology and Visual Science. S642-S642. 1995
    1995 STRUCTURAL FEATURES OF THE NONCATALYTIC CGMP BINDING-SITES IN FROG ROD PHOSPHODIESTERASE DETERMINED WITH CGMP ANALOGS.  Investigative Ophthalmology and Visual Science. S269-S269. 1995
    1987 GUANYLATE-CYCLASE ACTIVITY IN SQUID PHOTORECEPTOR-MEMBRANES.  Biophysical Journal. A269-A269. 1987
    1985 INVOLVEMENT OF CGMP IN PHOTOTRANSDUCTION BY ISOLATED FROG RODS IN THE ABSENCE OF TRANSMEMBRANE CALCIUM GRADIENTS.  Biophysical Journal. A100-A100. 1985
    1984 KINETIC MEASUREMENT OF CGMP CHANGES IN INTACT PHOTORECEPTORS.  Biophysical Journal. A1-A1. 1984
    1980 HEAD-TO-TAIL POLYMERIZATION OF MICROTUBULES INVITRO.  The FASEB Journal. 1818-1818. 1980

    Patent

    Year Title
    Methods of Identification and Use of Nematicide Compounds

    Teaching Activities

  • Doctoral Thesis Taught course 2023
  • Protein Biochemistry Lab Taught course 2023
  • Protein Biochemistry Lab Taught course 2023
  • Doctoral Thesis Taught course 2022
  • Senior Honors Thesis Taught course 2022
  • Intro Careers in Biotechnology Taught course 2022
  • Doctoral Thesis Taught course 2022
  • Protein Biochemistry Lab Taught course 2022
  • Protein Biochemistry Lab Taught course 2022
  • Senior Honors Thesis Taught course 2022
  • Doctoral Thesis Taught course 2021
  • Doctoral Thesis Taught course 2021
  • Lab Biochem & Molecular Biol Taught course 2021
  • Doctoral Thesis Taught course 2020
  • Doctoral Thesis Taught course 2020
  • General Biochemistry Taught course 2020
  • General Biochemistry Taught course 2020
  • Lab Biochem & Molecular Biol Taught course 2020
  • Doctoral Thesis Taught course 2019
  • Doctoral Thesis Taught course 2019
  • Doctoral Thesis Taught course 2018
  • Doctoral Research Taught course 2018
  • Doctoral Research Taught course 2018
  • Honors Senior Thesis Taught course 2018
  • Honors Senior Thesis Taught course 2018
  • Doctoral Research Taught course 2017
  • Honors Senior Thesis Taught course 2017
  • Honors Senior Thesis Taught course 2017
  • Rsrch Exp/MCBS Taught course 2017
  • Doctoral Research Taught course 2017
  • Doctoral Research Taught course 2017
  • Doctoral Research Taught course 2016
  • Tissue Engineering Taught course 2016
  • Tissue Engineering Taught course 2016
  • Doctoral Research Taught course 2016
  • Doctoral Research Taught course 2015
  • Honors Senior Thesis Taught course 2015
  • Doctoral Research Taught course 2015
  • Doctoral Research Taught course 2014
  • Doctoral Research Taught course 2014
  • Seminar Taught course 2014
  • Seminar Taught course 2014
  • Seminar/Integrated Physiology Taught course 2014

    • Education And Training

  • B.S. Biology-Chemistry, Tufts University
  • Ph.D. Molecular Biology, University of Wisconsin

    • Full Name

  • Rick Cote

    • Mailing Address

  • University of New Hampshire

    Molecular, Cellular, and Biomedical Sciences

    46 College Rd

    Durham, NH  03824

    United States