My current research focuses on the molecular and genetic analysis of the nervous system, more specifically the structure and function of neurotransmitter receptors and ion channels and their modulation by protein kinases and G-proteins.
We are interested in studying the molecular mechanisms by which neurons transmit, receive and store information in the mammalian central nervous system. Neurons communicate with each other using a combination of electrical and chemical signalling. The molecules which mediate this signalling are voltage-gated ion channels and neurotransmitter receptors.
In our major project we have isolated a family of neuronal cDNAs that encode voltage-gated calcium channels. Current work includes the characterization of the molecular and sub-cellular localization of calcium channel sub-types in the nervous system, and the analysis of the functional properties and modulation of calcium channel subtypes in a number of exogenous expression systems. In another project we have isolated mutations in unc-2, a gene encoding a neuronal calcium channel in the nematode Caenorhabditis elegans. Upon intro-duction of the identified point mutations into a rat homologue it is apparent that single amino acid substitutions can dramatically alter calcium channel biophysical properties. Current work includes the identification of extragenic revertants in order to define novel gene products that affect calcium channel function in vivo.
Other projects include the study of G-proteins and kinases involved in modulation of calcium channels, the use of the yeast 2-hybrid system to identify novel proteins that interact with calcium channels, and also the knock-out of ion channel and receptor gene expression using anti-sense techniques in cultured cells and animals.
Contributions of T-type calcium channel isoforms to neuronal firing. Channels. 4(6): 475-482.
Cain SM and TP Snutch (2010)
Contribution of calcium-dependent facilitation to synaptic plasticity revealed by migraine mutations in the P/Q-type calcium channel. Proc Natl Acad Sci U S A.107:18694-18699.
Adams, PJ, RL Rungta, E Garcia, AM van den Maagdenberg, BA MacVicar and TP Snutch (2010)
Contributions of T-Type Voltage-Gated Calcium Channels to Postsynaptic Calcium Signaling within Purkinje Neurons. Cerebellum. 2010 Aug 24, in press
Isope, P, ME Hildebrand and TP Snutch (2010)
Splice-variant changes of the Ca(V)3.2 T-type calcium channel mediate voltage-dependent facilitation and associate with cardiac hypertrophy and development. Channels 4(5): 375 – 389.
David, LS, E Garcia, SM Cain, EM Thau, Tyson JR and TP Snutch (2010)
The transient receptor potential channel antagonist SKF96365 is a potent blocker of low-voltage-activated T-type calcium channels. British Journal of Pharmacology 160:1464-1475.
Singh, A, ME Hildebrand, E Garcia, TP SNUTCH (2010)
Analgesic Effects of a Substituted N-Triazole Oxindole (TROX-1), a State-Dependant Cav2 Calcium Channel Blocker. Journal of Pharmacology Experimental Therapeutics 334:545-555.
Abbadie, C, OB McManus, SY Sun, RM Bugianesi, G Dai, RJ Haedo, JB Herrington, GJ Kaczoroski, MM Smith, AM Swensen, VA Warren, B Williams, SP Arneric, C Eduljee, TP Snutch, EW Tringham, N Jochnowitz, A Liang, E Macintyre, E McGowan, S Mistry, VV White, SB Hoyt, C London, KA Lyons, PB Bunting, S Volksdorf, JL Duffy (2010)
Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors. Bioorganic and Medicinal Chemistry Letters 20: 1378-83. Epub 2010 Jan 7
Pajouhesh, H, ZP Feng, Y Ding, L Zhang, H Pajouhesh, JL Morrison, F Belardetti, E Tringham, E Simonson, TW Vanderah, F Porreca, GW Zamponi, LA Mitscher, TP SNUTCH (2010)
Treatments for Neuropathic Pain Differentially Affect Delayed Matching Accuracy by Macaques: Effects of Amitriptyline and Gabapentin. Pain 148:446-453. Epub 2010 Jan 25
Buccafusco, JJ, AV Terry, Jr., A Vazdarjanova, TP SNUTCH and SP Arneric (2009)
Scaffold-based design and synthesis of potent N-type calcium channel blockers. Bioorganic and Medicinal Chemistry Letters 19: 6467-6472
Zamponi, GW, ZP Feng, L Zhang, H Pajouhesh, Yanbing Ding, F Belardetti, H Pajouhesh, D Dolphin, LA Mitscher and TP SNUTCH (2009)
Sarrazin Award, Canadian Physiological Society
Fellow, Canadian Academy of Health Sciences
Degree of Doctor of Science, honoris causa, Simon Fraser University, Canada
Life Sciences Company of the Year, BC Biotech Association
PolyPops Foundation Award, The Society for Biomolecular Screening
Canada Research Chair, Tier 1 -Biotechnology and Genomics-Neurobiology,
New Frontiers in Research Award, BC Innovation Council
Researcher of the Year Award, BC Biotech Association
Raymond and Beverly Sackler Distinguished Visiting Neuroscientist, University of Toronto
Canada's Top 10 Life Sciences Investment/Partnering Prospects Award, Ottawa Life Sciences Council
Induction, Fellow Royal Society of Canada
CIHR Senior Investigator Award, Canadian Institutes of Health Research
Keynote Address, UCSF Annual Neuroscience Retreat, Asilomar, CA
Steacie Prize, Steacie Memorial Fund Canada's most prestigious award for young scientists and engineers
International Albrecht Fleckenstein Award - presented by Bayer AG, Germany, for novel and significant research in the field of calcium channel pharmacology and modulation
MRC Scientist, Medical Research Council of Canada