Melanie Kelly, PhD
BSc, PhD (Southampton)
Ocular pharmacology, G protein-coupled receptors, cell signaling, ion channels, glaucoma and retinal disease.
I am one of 5 vision researchers housed in a collaborative multidisciplinary laboratory, The laboratory for Retina and Optic Nerve Research, within the Faculty of Medicine, Dalhousie University. Researchers in this joint research laboratory are involved in all aspects of vision research and have a mandate to understand normal retinal signal processing as well as retinal pathophysiology. Facilities include approximately 6000 sq feet of shared and personal laboratory space including offices. The laboratory has dedicated facilities for molecular biology and biochemistry, sterile cell culture, electrophysiology, microscopy and includes a small surgical suite and preparation room. Currently, in addition to the 5 primary faculty members, the Laboratory for Retina and Optic Nerve Research is home to 4 senior research technicians, 2 postdoctoral fellows and 10 graduate and undergraduate students.
My primary research interests are molecular pharmacology and receptors. Ongoing research deals with the pharmacology of aqueous humor secretion and outflow in the mammalian eye. Individual research projects address intramembrane interactions between G protein-coupled receptors as well as the receptor-coupled signal transduction. Specific projects are examining how ligands, such as cannabinoids and adrenoreceptor agonists, affect the production and drainage of aqueous humor and whether interactions between receptors and signaling pathways can give rise to novel pharmacology. Experimental approaches involve molecular and biochemical assays for identifying receptor proteins and enzyme activity as well as biophysical approaches such as bioluminescence resonance energy transfer (BRET), fluorescence energy transfer (FRET), fluorescent ion imaging and patch-clamp electrophysiology to look at protein interactions and signal transduction in live cells and tissue. This work has implications for the development of novel ocular hypotensive agents for the treatment of glaucoma, a blinding eye disease in which the primary modifiable risk factor is increased intraocular pressure arising from defective aqueous humor dynamics.
Interactive projects with collaborators in the Laboratory for Retina and Optic Nerve Research include: studies of the developmental regulation of ion channels in retinal stem cells and progenitors, investigations into the role of retinal glial cells in modulating phototransduction, and in vivo and in vitro studies of retinal ganglion cell function and vision in animals models of retinal pathology.
Shi, C., Szczesniak, A., Mao, L., Jollimore, C., Coca-Prados, M., Hung, O., and Kelly, M.E.M. (2003). A3 Adenosine and CB1 receptors activate a PKC-sensitive Cl- current in human non-pigmented ciliary epithelial cells via a Gbeta gamma-coupled MAPK signaling pathway. Brit. J. Pharmacol. 139: 475-486.
Bertolesi, G.E., Shi, C., Elbaum, L., Jollimore, C.A.B., Denovan-Wright, E.A., Barnes, S., Kelly, M.E.M. (2003). Regulation of alpha1G T-type calcium channel gene (CACNA1G) expression during neuronal differentiation. Eur. J. Neurosci. 17: 1802-1810.
Bertolesi, G.E., Shi, C., Elbaum, L., Jollimore, C., Rozenberg, G., Barnes, S. and Kelly, M.E.M. (2002). The Ca2+ channel antagonists mibefradil and pimozide inhibit cell growth via different cytotoxic mechanisms. Mol. Pharmacol. 62: 119-210.
Shi, C., Barnes, S. Coca-Prados, M. and Kelly, M.E.M. (2002). Protein tyrosine kinase and protein phosphatase signaling pathways regulate volume-sensitive chloride currents in a nonpigmented ciliary epithelial cell line. Invest. Ophthalmol. Vis. Sci. 43: 1525-1532.
Baptiste, D., Hartwick, A., Jollimore, CAB., Baldridge, WH. Chauhan, BC., Tremblay, F. and Kelly, MEM. (2002). Comparison of the Neuroprotective effects of beta-adrenoceptor blockers and alpha2-adrenoceptor agonists in an in vitro retinal cell culture model and in isolated retina. Invest. Ophthalmol. Vis. Sci. 43: 2666-2676.
Title: Transmembrane signal transduction in vertebrate cells
Department of Pharmacology
Room 15A3, 15th Floor
Laboratory for Retina and Optic Nerve Research
Sir Charles Tupper Medical Building
5850 College Street
P.O. Box 15000
Halifax, Nova Scotia
Canada B3H 4R2