Dr. Rick Cote

Rick Cote

PROFESSOR
Director, Center of Integrated Biomedical and Bioengineering Research
Faculty Fellow, Research and Graduate Education
Phone: (603) 862-2458
Office: Molecular, Cellular, & Biomedical Sciences, Rudman Hall Rm 379, Durham, NH 03824
Websites:
Pronouns: He/him/his

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.

Faulty Award Winner

Award Type:  Distinguished Professor
Year:  2016

Courses Taught

  • BCHM/BMCB 855/755: Protein Biochemistry Lab
  • BMCB 658: General Biochemistry
  • BMCB 755: Protein Biochemistry Lab
  • BMS 799H: Senior Honors Thesis
  • MCBS 801: Intro Careers in Biotechnology
  • MCBS 999: Doctoral Thesis

Education

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

Research Interests

  • Biochemistry
  • Biochemistry, Proteins
  • Biomedical Research Resources, Other
  • Biomedical Research Training
  • Biomedical Research, Multidisciplinary
  • Biotechnology
  • Blindness
  • Catalysis/Kinetics
  • Cellular Physiology
  • Chromatography
  • Crop Protection (Pests, Diseases, & Weeds)
  • Drug Discovery
  • Enzymology
  • Eye Diseases
  • Gene Cloning
  • Molecular Biology
  • Molecular Cloning
  • Molecular Medicine
  • Nematology
  • Neurobiology
  • Neuropharmacology
  • Pharmacology
  • Preclinical Research
  • Proteins and Macromolecules
  • Proteomics
  • Receptors
  • Recombinant DNA
  • Research Training
  • Retinitis Pigmentosa
  • Science/Technology/Engineering/Math (STEM) Education
  • Scientific Instrumentation
  • Signal Transduction (Sensory/Cellular)
  • Structural Biology
  • University/Industrial Partnership
  • Vision
  • Vision Science

Selected Publications

  • Irwin, M., Wang, X., & Cote, R. (2022). Reconstitution of Membrane-associated Components of a G-protein Signaling Pathway on Membrane-coated Nanoparticles (Lipobeads). BIO-PROTOCOL, 12(2). doi:10.21769/BioProtoc.4303

  • Cote, R. H., Gupta, R., Irwin, M. J., & Wang, X. (2022). Photoreceptor Phosphodiesterase (PDE6): Structure, Regulatory Mechanisms, and Implications for Treatment of Retinal Diseases.. Adv Exp Med Biol, 1371, 33-59. doi:10.1007/5584_2021_649

  • Cote, R. H. (2021). Photoreceptor phosphodiesterase (PDE6): activation and inactivation mechanisms during visual transduction in rods and cones. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 473(9), 1377-1391. doi:10.1007/s00424-021-02562-x

  • Gupta, R., Liu, Y., Wang, H., Nordyke, C. T., Puterbaugh, R. Z., Cui, W., . . . Cote, R. H. (2020). Structural Analysis of the Regulatory GAF Domains of cGMP Phosphodiesterase Elucidates the Allosteric Communication Pathway. JOURNAL OF MOLECULAR BIOLOGY, 432(21), 5765-5783. doi:10.1016/j.jmb.2020.08.026

  • Irwin, M. J., Gupta, R., Gao, X. -Z., Cahill, K. B., Chu, F., & Cote, R. H. (2019). The molecular architecture of photoreceptor phosphodiesterase 6 (PDE6) with activated G protein elucidates the mechanism of visual excitation. JOURNAL OF BIOLOGICAL CHEMISTRY, 294(51), 19486-19497. doi:10.1074/jbc.RA119.011002

  • Chu, F., Hogan, D., Gupta, R., Gao, X. -Z., Nguyen, H. T., & Cote, R. H. (2019). Allosteric Regulation of Rod Photoreceptor Phosphodiesterase 6 (PDE6) Elucidated by Chemical Cross-Linking and Quantitative Mass Spectrometry. JOURNAL OF MOLECULAR BIOLOGY, 431(19), 3677-3689. doi:10.1016/j.jmb.2019.07.035

  • Wang, X., Plachetzki, D. C., & Cote, R. H. (2019). The N termini of the inhibitory -subunits of phosphodiesterase-6 (PDE6) from rod and cone photoreceptors differentially regulate transducin-mediated PDE6 activation. JOURNAL OF BIOLOGICAL CHEMISTRY, 294(21), 8351-8360. doi:10.1074/jbc.RA119.007520

  • Schuster, K. D., Mohammadi, M., Cahill, K. B., Matte, S. L., Maillet, A. D., Vashisth, H., & Cote, R. H. (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(3). doi:10.1371/journal.pone.0214554

  • Zeng-Elmore, X., Gao, X. -Z., Pellarin, R., Schneidman-Duhovny, D., Zhang, X. -J., Kozacka, K. A., . . . Chu, F. (2014). Molecular Architecture of Photoreceptor Phosphodiesterase Elucidated by Chemical Cross-Linking and Integrative Modeling. JOURNAL OF MOLECULAR BIOLOGY, 426(22), 3713-3728. doi:10.1016/j.jmb.2014.07.033

  • Cahill, K. B., Quade, J. H., Carleton, K. L., & Cote, R. H. (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(49), 41406-41416. doi:10.1074/jbc.M112.389189

  • Zhang, X. -J., Gao, X. -Z., Yao, W., & Cote, R. H. (2012). Functional Mapping of Interacting Regions of the Photoreceptor Phosphodiesterase (PDE6) gamma-Subunit with PDE6 Catalytic Dimer, Transducin, and Regulator of G-protein Signaling9-1 (RGS9-1). JOURNAL OF BIOLOGICAL CHEMISTRY, 287(31), 26312-26320. doi:10.1074/jbc.M112.377333

  • Matte, S. L., Laue, T. M., & Cote, R. H. (2012). Characterization of Conformational Changes and Protein-Protein Interactions of Rod Photoreceptor Phosphodiesterase (PDE6). JOURNAL OF BIOLOGICAL CHEMISTRY, 287(24), 20111-20121. doi:10.1074/jbc.M112.354647

  • Zhang, X. -J., Skiba, N. P., & Cote, R. H. (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(7), 4455-4463. doi:10.1074/jbc.M109.057406

  • Liu, Y. -T., Matte, S. L., Corbin, J. D., Francis, S. H., & Cote, R. H. (2009). Probing the Catalytic Sites and Activation Mechanism of Photoreceptor Phosphodiesterase Using Radiolabeled Phosphodiesterase Inhibitors. JOURNAL OF BIOLOGICAL CHEMISTRY, 284(46), 31541-31547. doi:10.1074/jbc.M109.018606

  • Zhang, X. -J., Cahill, K. B., Elfenbein, A., Arshavsky, V. Y., & Cote, R. H. (2008). Direct Allosteric Regulation between the GAF Domain and Catalytic Domain of Photoreceptor Phosphodiesterase PDE6. JOURNAL OF BIOLOGICAL CHEMISTRY, 283(44), 29699-29705. doi:10.1074/jbc.M803948200

  • Pentia, D. C., Hosier, S., & Cote, R. H. (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(9), 5500-5505. doi:10.1074/jbc.M507488200

  • Zhang, X. J., Feng, Q., & Cote, R. H. (2005). Efficacy and selectivity of phosphodiesterase-targeted drugs in inhibiting photoreceptor phosphodiesterase (PDE6) in retinal photoreceptors. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 46(9), 3060-3066. doi:10.1167/iovs.05-0257

  • Carleton, K. L., Spady, T. C., & Cote, R. H. (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(1), 75-89. doi:10.1007/s00239-004-0289-z

  • Zhang, X. J., & Cote, R. H. (2005). cGMP signaling in vertebrate retinal photoreceptor cells. FRONTIERS IN BIOSCIENCE-LANDMARK, 10, 1191-1204. doi:10.2741/1612

  • Norton, A. W., Hosier, S., Terew, J. M., Li, N., Dhingra, A., Vardi, N., . . . Cote, R. H. (2005). Evaluation of the 17-kDa prenyl-binding protein as a regulatory protein for phototransduction in retinal photoreceptors. JOURNAL OF BIOLOGICAL CHEMISTRY, 280(2), 1248-1256. doi:10.1074/jbc.M410475200

  • Pentia, D. C., Hosier, S., Collupy, R. A., Valeriani, B. A., & Cote, R. H. (2005). Purification of PDE6 isozymes from mammalian retina.. Methods Mol Biol, 307, 125-140. doi:10.1385/1-59259-839-0:125

  • Cote, R. H. (2005). Cyclic guanosine 5'-monophosphate binding to regulatory GAF domains of photoreceptor phosphodiesterase.. Methods Mol Biol, 307, 141-154. doi:10.1385/1-59259-839-0:141

  • Cote, R. H. (2004). Characteristics of Photoreceptor PDE (PDE6): similarities and differences to PDE5. INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH, 16, S28-S33. doi:10.1038/sj.ijir.3901212

  • Paglia, M. J., Mou, H., & Cote, R. H. (2002). Regulation of photoreceptor phosphodiesterase (PDE6) by phosphorylation of its inhibitory gamma subunit re-evaluated. JOURNAL OF BIOLOGICAL CHEMISTRY, 277(7), 5017-5023. doi:10.1074/jbc.M106328200

  • Mou, H. M., & Cote, R. H. (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(29), 27527-27534. doi:10.1074/jbc.M103316200

  • Tcheudji, J. F. K., Lebeau, L., Virmaux, N., Maftei, C. G., Cote, R. H., Lugnier, C., & Schultz, P. (2001). Molecular organization of bovine rod cGMP-phosphodiesterase 6. JOURNAL OF MOLECULAR BIOLOGY, 310(4), 781-791. doi:10.1006/jmbi.2001.4813

  • Norton, A. W., D'Amours, M. R., Grazio, H. J., Hebert, T. L., & Cote, R. H. (2000). Mechanism of transducin activation of frog rod photoreceptor phosphodiesterase - Allosteric interactions between the inhibitory gamma subunit and the noncatalytic cGMP-binding sites. JOURNAL OF BIOLOGICAL CHEMISTRY, 275(49), 38611-38619. doi:10.1074/jbc.M004606200

  • Cote, R. H. (2000). Kinetics and regulation of cGMP binding to noncatalytic binding sites on photoreceptor phosphodiesterase. VERTEBRATE PHOTOTRANSDUCTION AND THE VISUAL CYCLE, PART A, 315, 646-672. Retrieved from https://www.webofscience.com/

  • Mou, H. M., Grazio, H. J., Cook, T. A., Beavo, J. A., & Cote, R. H. (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(26), 18813-18820. doi:10.1074/jbc.274.26.18813

  • D'Amours, M. R., & Cote, R. H. (1999). Regulation of photoreceptor phosphodiesterase catalysis by its non-catalytic cGMP-binding sites. BIOCHEMICAL JOURNAL, 340, 863-869. doi:10.1042/0264-6021:3400863

  • D'Amours, M. R., Granovsky, A. E., Artemyev, N. O., & Cote, R. H. (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(3), 508-514. Retrieved from https://www.webofscience.com/

  • Hebert, M. C., Schwede, F., Jastorff, B., & Cote, R. H. (1998). Structural features of the noncatalytic cGMP binding sites of frog photoreceptor phosphodiesterase using cGMP analogs. JOURNAL OF BIOLOGICAL CHEMISTRY, 273(10), 5557-5565. doi:10.1074/jbc.273.10.5557

  • Artemyev, N. O., Arshavsky, V. Y., & Cote, R. H. (1998). Photoreceptor phosphodiesterase: Interaction of inhibitory gamma subunit and cyclic GMP with specific binding sites on catalytic subunits. METHODS, 14(1), 93-104. doi:10.1006/meth.1997.0568

  • COTE, R. H., BOWNDS, M. D., & ARSHAVSKY, V. Y. (1994). CGMP BINDING-SITES ON PHOTORECEPTOR PHOSPHODIESTERASE - ROLE IN FEEDBACK-REGULATION OF VISUAL TRANSDUCTION. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 91(11), 4845-4849. doi:10.1073/pnas.91.11.4845

  • COTE, R. H., & BRUNNOCK, M. A. (1993). INTRACELLULAR CGMP CONCENTRATION IN ROD PHOTORECEPTORS IS REGULATED BY BINDING TO HIGH AND MODERATE AFFINITY CGMP BINDING-SITES. JOURNAL OF BIOLOGICAL CHEMISTRY, 268(23), 17190-17198. Retrieved from https://www.webofscience.com/

  • COTE, R. H., NICOL, G. D., BURKE, S. A., & BOWNDS, M. D. (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(26), 15384-15391. Retrieved from https://www.webofscience.com/

  • ROBINSON, P. R., & COTE, R. H. (1989). CHARACTERIZATION OF GUANYLATE-CYCLASE IN SQUID PHOTORECEPTORS. VISUAL NEUROSCIENCE, 3(1), 1-7. doi:10.1017/S0952523800012451

  • COTE, R. H., NICOL, G. D., BURKE, S. A., & BOWNDS, M. D. (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(28), 2965-2975. Retrieved from https://www.webofscience.com/

  • Cote, R. H., Nicol, G. D., Burke, S. A., & Bownds, M. D. (1986). Changes in cGMP concentration correlate with some, but not all, aspects of the light-regulated conductance of frog rod photoreceptors.. J Biol Chem, 261(28), 12965-12975. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/3020017

  • ROBINSON, P. R., RADEKE, M. J., COTE, R. H., & BOWNDS, M. D. (1986). CGMP INFLUENCES GUANINE-NUCLEOTIDE BINDING TO FROG PHOTORECEPTOR G-PROTEIN. JOURNAL OF BIOLOGICAL CHEMISTRY, 261(1), 313-318. Retrieved from https://www.webofscience.com/

  • COTE, R. H., BIERNBAUM, M. S., NICOL, G. D., & BOWNDS, M. D. (1984). LIGHT-INDUCED DECREASES IN CGMP CONCENTRATION PRECEDE CHANGES IN MEMBRANE-PERMEABILITY IN FROG ROD PHOTORECEPTORS. JOURNAL OF BIOLOGICAL CHEMISTRY, 259(15), 9635-9641. Retrieved from https://www.webofscience.com/

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