Ronald G. Gregg, Ph.D.

Professor; Department Chair

Department of Biochemistry and Molecular Biology

319 Abraham Flexner Way, HSC-A, Room 616 502-852-5217 502-852-4687 (lab) 502-852-4112 (fax)

DNA Core

Research Interests

Synaptogenesis and development in the retina

Laboratory Personnel

Elizabeth Hudson

Tom Ray

Timothy Hoffman

Rui Ji

Nazaral Hasan

The long term goal of my research is to understand the molecular events that underlie the formation and function of one of the synaptic layers, the outer plexiform layer (OPL), in the retina. This synapse connects the photoreceptors that collect light and convert it into an electrical signal, to the second order neurons, bipolar and horizontal cells. Early in development the pre- and post-synaptic neurons make contact and begin to form a synapse. This initial contact triggers a series of events that results in a synapse of extraordinary complexity. Three dendrites from post-synaptic neurons invaginate into the axon terminal of the presynaptic cell, which is the photoreceptor in this case. We have discovered a mutant mouse that fails to undergo normal maturation of the synapse and results in night blindness. This model is being used to determine what signals are involved in the maturation of this important synapse.

In a second project, we focus on the molecular components of the signal transduction cascade in the depolarizing bipolar cells. These cells utilize a metabotropic glutamate receptor, GRM6, to modulate the activity of the non-specific cation channel, TRPM1. My lab is investigating how several proteins, GRM6, TRPM1, GPR179, nyctalopin and LRIT3 interact to form a functional

Selected Publications

Peachey NS, Pearring JN, Bojang P Jr, Hirschtritt ME, Sturgill-Short G, Ray TA, Furukawa T, Koike C, Goldberg AF, Shen Y, McCall MA, Nawy S, Nishina PM, Gregg RG. Depolarizing bipolar cell dysfunction due to a Trpm1 point mutation. J  Neurophysiol. 2012 Nov;108(9):2442-51. doi: 10.1152/jn.00137.2012. Epub 2012 Aug  15. PubMed PMID: 22896717.

Wilburn DB, Bowen KE, Gregg RG, Cai J, Feldhoff PW, Houck LD, Feldhoff RC. Proteomic and UTR analyses of a rapidly evolving hypervariable family of vertebrate pheromones. Evolution. 2012 Jul;66(7):2227-39. doi: 10.1111/j.1558-5646.2011.01572.x. Epub 2012 Feb 17. PubMed PMID: 22759298.

Orlandi C, Posokhova E, Masuho I, Ray TA, Hasan N, Gregg RG, Martemyanov KA. GPR158/179 regulate G protein signaling by controlling localization and activity  of the RGS7 complexes. J Cell Biol. 2012 Jun 11;197(6):711-9. doi: 10.1083/jcb.201202123. PubMed PMID: 22689652; PubMed Central PMCID: PMC3373406.

Bojang P Jr, Gregg RG. Topological analysis of small leucine-rich repeat proteoglycan nyctalopin. PLoS One. 2012;7(4):e33137. doi: 10.1371/journal.pone.0033137. Epub 2012 Apr 2. PubMed PMID: 22485138; PubMed Central PMCID: PMC3317652.

Peachey NS, Ray TA, Florijn R, Rowe LB, Sjoerdsma T, Contreras-Alcantara S, Baba K, Tosini G, Pozdeyev N, Iuvone PM, Bojang P Jr, Pearring JN, Simonsz HJ, van Genderen M, Birch DG, Traboulsi EI, Dorfman A, Lopez I, Ren H, Goldberg AF, Nishina PM, Lachapelle P, McCall MA, Koenekoop RK, Bergen AA, Kamermans M, Gregg RG. (2012) GPR179 is required for depolarizing bipolar cell function and is mutated in autosomal-recessive complete congenital stationary night blindness. Am J Hum Genet. 2012 Feb 10;90(2):331-9.

Ball SL, McEnery MW, Yunker AM, Shin HS, Gregg RG. (2011) Distribution of voltage gated calcium channel ß subunits in the mouse retina. Brain Res. 2011 Sep 15;1412:1-8. Epub 2011 Jul 23.

Pearring JN, Bojang P Jr, Shen Y, Koike C, Furukawa T, Nawy S, Gregg RG. (2011) A role for nyctalopin, a small leucine-rich repeat protein, in localizing the TRP melastatin 1 channel to retinal depolarizing bipolar cell dendrites. J Neurosci. 2011 Jul 6;31(27):10060-6.

Dhingra A, Fina ME, Neinstein A, Ramsey DJ, Xu Y, Fishman GA, Alexander KR, Qian H, Peachey NS, Gregg RG, Vardi N. (2011) Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of retinal ON bipolar cells. J Neurosci. 2011 Mar 16;31(11):3962-7.

Neef J, Gehrt A, Bulankina AV, Meyer AC, Riedel D, Gregg RG, Strenzke N, Moser T. (2009) The Ca2+ channel subunit beta2 regulates Ca2+ channel abundance and function in inner hair cells and is required for hearing. J Neurosci. 2009 Aug 26;29(34):10730-40.

Shen Y, Heimel JA, Kamermans M, Peachey NS, Gregg RG, Nawy S. (2009) A transient receptor potential-like channel mediates synaptic transmission in rod bipolar cells. J Neurosci 2009 May 13;29(19):6088-93.

Maddox DM, Vessey KA, Yarbrough GL, Invergo BM, Cantrell DR, Inayat S, Balannik V, Hicks WL, Hawes NL, Byers S, Smith RS, Hurd R, Howell D, Gregg RG, Chang B, Naggert JK, Troy JB, Pinto LH, Nishina PM, McCall MA. (2008) Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses. J Physiol. 2008 Sep 15;586(Pt 18):4409-24. Epub 2008 Aug 7.

McCall MA, Gregg RG. (2008) Comparisons of structural and functional abnormalities in mouse b-wave mutants. J Physiol. 2008 Sep 15;586(Pt 18):4385-92. Epub 2008 Jul 24. Review.

Lee J, Willer JR, Willer GB, Smith K, Gregg RG, Gross JM. (2008) Zebrafish blowout provides genetic evidence for Patched1-mediated negative regulation of Hedgehog signaling within the proximal optic vesicle of the vertebrate eye. Dev Biol. 2008 Jul 1;319(1):10-22. Epub 2008 Apr 4. PMID: 18479681 [PubMed - indexed for MEDLINE]

Gregg RG, Kamermans M, Klooster J, Lukasiewicz PD, Peachey NS, Vessey KA, McCall MA.(2007. Nyctalopin expression in retinal bipolar cells restores visual function in a mouse model of complete X-linked congenital stationary night blindness. J Neurophysiol. 2007 Nov. 98(5):3023-33.

Palmer, C.A., Hollis, D.M., Watts, R.A., Houck, L.D., McCall, M.A., Gregg, R.G., Feldhoff, P.W., Feldhoff, R.C., Arnold, S.J. (2007). Plethodontid modulating factor, a hypervariable salamander courtship pheromone in the three-finger protein superfamily. FEBS J. 274:2300-2310.

Demas, J., Sagdullaev, B.T., Green, E., Jaubert-Miazza, L., McCall, M.A., Gregg, R.G., Wong, R.O., Guido, W. (2006). Failure to Maintain Eye-Specific Segregation in nob, a Mutant with Abnormally Patterned Retinal Activity. Neuron. 50:247-59.

Schroeter, E.H., Wong, R.O.L., Gregg R.G. (2006). In vivo development of retinal bipolar cell axonal terminals visualized in nyx::MYFP transgenic zebrafish. Visual Neuroscience, 23, 833–843.

Marmorstein, L.Y., Wu, J., McLaughlin, P., Yocom, J., Karl, M.O., Neussert, R., Wimmers, S., Stanton, J.B., Gregg, R.G., Strauss, O., Peachey, N.S., Marmorstein, A.D. (2006). The Light Peak of the Electroretinogram Is Dependent on Voltage-gated Calcium Channels and Antagonized by Bestrophin (Best-1). J. Gen. Physiol. 127:577-89.

Chang, B., Heckenlively, J.R., Bayley, P.R., Brecha, N.C., Davisson, M.T., Hawes, N.L., Hirano, A.A., Hurd, R.E., Ikeda, A., Johnson, B.A., McCall, M.A., Morgans, C.W., Nusinowitz, S., Peachey, N.S., Rice, D.S., Vessey, K.A. and Gregg, R.G. (2006). The nob2 mouse, a null mutation in Cacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses. Visual Neuroscience 23:11-24.

Semina, E.V., Bosenko, D.V., Zinkevich, N.A., Soules, K.A., Halloran, M.C., Vihtelic, T.C., Willer, G.B., Gregg, R.G., Link, B.A. (2006) Mutations in laminin alpha 1 result in complex ocular phenotypes in zebrafish. Developmental Biology. Dev. Biol. 299, 63-77

Palmer, C.A., Watts, R.A., Gregg, R.G., McCall, M.A., Houck, L.D., Highton, R., Arnold, S.J. (2005). Lineage-Specific Differences in Evolutionary Mode in a Salamander Courtship Pheromone. Mol Biol Evol. 22:2243-2256.

Willer, G.B., Lee, V.M., Gregg, R.G., Link, B.A. (2005) Analysis of the zebrafish perplexed mutation reveals tissue specific roles for de novo pyrimidine synthesis during development.Genetics. 170:1827-37.

Liem, E.B., Lin, C.-M., Suleman, M-I., Doufas, A.G., Gregg, R.G., Veauthier, J.M., Loyd,G., Sessler, D.I. (2004) Anesthetic requirement is increased in redheads. (2004). Anesthesiology 101:279-83.

Arikkath,J., Chen,C.C., Ahern,C., Allamand,V., Flanagan,J.D., Coronado,R., Gregg,R.G., and Campbell,K.P. (2003). Gamma 1 subunit interactions within the skeletal muscle L-type voltage-gated calcium channels. J. Biol. Chem. 278, 1212-1219.

Ball,S.L., Pardue,M.T., McCall,M.A., Gregg,R.G., and Peachey,N.S. (2003). Immunohistochemical analysis of the outer plexiform layer in the nob mouse shows no abnormalities. Vis. Neurosci. 20, 267-272.

Gregg,R.G., Willer,G.B., Fadool,J.M., Dowling,J.E., and Link,B.A. (2003). Positional cloning of the young mutation identifies an essential role for the Brahma chromatin remodeling complex in mediating retinal cell differentiation. Proc. Natl. Acad. Sci. U. S. A 100, 6535-6540.

Gregg,R.G., Mukhopadhyay,S., Candille,S.I., Ball,S.L., Pardue,M.T., McCall,M.A., and Peachey,N.S. (2003). Identification of the gene and the mutation responsible for the mouse nob phenotype. Invest Ophthalmol. Vis. Sci. 44, 378-384.

Morris,C.A., Mervis,C.B., Hobart,H.H., Gregg,R.G., Bertrand,J., Ensing,G.J., Sommer,A., Moore,C.A., Hopkin,R.J., Spallone,P.A., Keating,M.T., Osborne,L., Kimberley,K.W., and Stock,A.D. (2003). GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-phenotype analysis of five families with deletions in the Williams syndrome region. Am. J. Med. Genet. 123A, 45-59.

Ball,S.L., Powers,P.A., Shin,H.S., Morgans,C.W., Peachey,N.S., and Gregg,R.G. (2002). Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer. Invest Ophthalmol. Vis. Sci. 43, 1595-1603.

Ball,S.L. and Gregg,R.G. (2002). Using mutant mice to study the role of voltage-gated calcium channels in the retina. Adv. Exp. Med. Biol. 514, 439-450.

McCall,M.A., Lukasiewicz,P.D., Gregg,R.G., and Peachey,N.S. (2002). Elimination of the rho1 subunit abolishes GABA(C) receptor expression and alters visual processing in the mouse retina. J. Neurosci. 22, 4163-4174.

Read,D.S., McCall,M.A., and Gregg,R.G. (2002). Absence of voltage-dependent calcium channels delays photoreceptor degeneration in rd mice. Exp. Eye Res. 75, 415-420.