Weiss, Sam - University of Calgary - Department of Cell Biology and Anatomy

个人简介

Dr. Samuel Weiss is Professor, AI-HS Scientist and Director of the Hotchkiss Brain Institute at the Cumming School of Medicine at the University of Calgary. In 1985, Dr. Weiss co-discovered the metabotropic glutamate receptor – and in 1992, he discovered neural stem cells in the brains of adult mammals. He chairs national and international advisory committees, has authored many publications, holds key patents in the neural stem cell field and has founded three biotechnology companies. In 2008, Dr. Weiss was named recipient of a Gairdner International Award "for his seminal discovery of adult neural stem cells in the mammalian brain and its importance in nerve cell regeneration" and in 2009, he was elected as a Fellow of the Royal Society of Canada.

研究领域

Brain Tumour Stem Cell Biology and Experimental Therapeutics My laboratory discovered a mammalian central nervous system (CNS) stem cell that can be induced to divide in cell culture and in the intact brain, and produce the three major cell types of the CNS - neurons, astrocytes and oligodendrocytes. Remarkably, this CNS stem cell is present in both embryonic and adult mammalian (from rodent to human) brain. Recent evidence suggests that the adult human brain stem cells may be at the origin of the malignant human brain tumour – glioblastoma multiforme (glioma). Thus, the current research goal of the Weiss laboratory is to gain insights into the aberrant cell biology mechanisms of human brain tumour stem cells (BTSCs) that may lead to brain tumour initiation, therapeutic resistance and recurrence. During the past few years, we have established close to 100 BTSC lines from human glioma patients. These BTSC lines display many of the fundamental characteristics of stem cells such as ability to grow as neurospheres under serum-free conditions, multilineage differentiation and clonogenicity. Importantly, they maintain the key parental tumour mutations and mimic human tumour growth in vivo in orthotopic xenografts in NOD SCID mice. We were the first group to report the establishment of BTSC lines with endogenous expression of the IDH1 mutant enzyme and our BTSC library has lines with many of the key characteristic mutations reported in glioma. We employ a combination of cell biological, molecular, biochemical, and genomic approaches and use BTSCs as a model to study glioma biology and therapeutic response in vitro and in vivo. We are currently focused on four major areas of research: 1. The mechanisms of autocrine growth factor signalling in BTSCs leading to uncontrolled growth in brain tumours 2. The "stemness" factor - investigating the cell biology of BTSCs to understand disease initiation and recurrence 3. Intracellular oncogenic signalling pathways in BTSCs and a translational approach to experimental therapeutics and new drug therapy for brain tumours 4. Understanding BTSC metabolism with a special focus on the IDH1/2 mutation We believe the BTSC model system is a powerful tool to investigate human glioma biology and develop novel experimental therapeutics for the disease.

近期论文

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Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA. Shuai Liua, Andrea K. Globab, Fergil Millsb, Lindsay Naefa, Min Qiaoa, Shernaz X. Bamjib, and Stephanie L. Borgland. Proceedings of the National Academy of Sciences of the United States of America 2016 Feb 15. doi: 10.1073/pnas.1515724113 Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity. Nicholas L Weilinger, Alexander W Lohman, Brooke D Rakai, Evelyn M M Ma, Jennifer Bialecki, Valentyna Maslieieva, Travis Rilea, Mischa V Bandet, Nathan T Ikuta, Lucas Scott, Michael A Colicos, G Campbell Teskey, Ian R Winship & Roger J Thompson. Nature Neuroscience 2016 Feb 8. doi:10.1038/nn.4236;PMID:26854804 Tonic Local Brain Blood Flow Control by Astrocytes Independent of Phasic Neurovascular Coupling. Rosenegger DG, Tran CH, Wamsteeker Cusulin JI, Gordon GR. J Neurosci. 2015 Sep 30;35(39):13463-74. doi: 10.1523/JNEUROSCI.1780-15.2015. PMID: 26424891 Role of Prelimbic GABAergic Circuits in Sensory and Emotional Aspects of Neuropathic Pain. Zhang Z, Gadotti VM, Chen L1, Souza IA, Stemkowski PL, Zamponi GW.Cell Rep. 2015 Aug 4;12(5):752-759. doi: 10.1016/j.celrep.2015.07.001. Epub 2015 Jul 23. PMID: 26212331 Orexin Signaling in the VTA Gates Morphine-Induced Synaptic Plasticity. Baimel C, Borgland SL. J Neurosci. 2015 May 6;35(18):7295-303. doi: 10.1523/JNEUROSCI.4385-14.2015. PMID: 25948277 CaV1.2/CaV3.x channels mediate divergent vasomotor responses in human cerebral arteries. Harraz OF, Visser F, Brett SE, Goldman D, Zechariah A, Hashad AM, Menon BK, Watson T, Starreveld Y, Welsh DG. J Gen Physiol. 2015 May;145(5):405-18. doi: 10.1085/jgp.201511361. PMID: 25918359 IKCa Channels Are a Critical Determinant of the Slow AHP in CA1 Pyramidal Neurons. Brian King, Arsalan P. Rizwan, Hadhimulya Asmara, Norman C. Heath, Jordan D.T. Engbers, Steven Dykstra, Theodore M. Bartoletti, Shahid Hameed, Gerald W. Zamponi, Ray W. Turner. Cell Rep. 2015 Apr 14;11(2):175-82. PMID: 25865881 Application of fast-track surgery principles to evaluate effects of atipamezole on recovery and analgesia following ovariohysterectomy in cats anesthetized with dexmedetomidine-ketamine-hydromorphone. Hasiuk MM, Brown D, Cooney C, Gunn M, Pang DS. J Am Vet Med Assoc. 2015 Mar 15;246(6):645-53. doi: 10.2460/javma.246.6.645. PMID: 25719847 FAAH genetic variation enhances fronto-amygdala function in mouse and human. Dincheva I, Drysdale AT, Hartley CA, Johnson DC, Jing D, King EC, Ra S, Gray JM, Yang R, DeGruccio AM, Huang C, Cravatt BF, Glatt CE, Hill MN, Casey BJ1, Lee FS. Nat Commun. 2015 Mar 3;6:6395. doi: 10.1038/ncomms7395. PMID: 25731744 Emerging roles for enteric glia in gastrointestinal disorders. Sharkey KA. J Clin Invest. 2015 Feb 17. pii: 76303. doi: 10.1172/JCI76303.PMID: 25689252 Efficacy of a portable oxygen concentrator with pulsed delivery for treatment of hypoxemia during equine field anesthesia. Coutu P, Caulkett N, Pang D, Boysen S.Vet Anaesth Analg. 2015 Feb 14. doi: 10.1111/vaa.12246. PMID: 25683480 Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation. Bashashati M, Nasser Y, Keenan C, Ho W, Piscitelli F, Nalli M, Mackie K, Storr M, Di Marzo V, Sharkey K.A. Br J Pharmacol. 2015 Feb 12. doi: 10.1111/bph.13114. [Epub ahead of print] PMID: 25684407 Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke. Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; the ESCAPE Trial Investigators. N Engl J Med. 2015 Feb 11. PMID: 25671798 Intestinal Microbiota: a Regulator of Intestinal Inflammation and Cardiac Ischemia? Bashashati M, Habibi HR, Keshavarzian A, Schmulson M, Sharkey KA. Curr Drug Targets. 2015 Jan 19. [Epub ahead of print] PMID: 25601328 Orally administered indomethacin acutely reduces cellular prion protein in the small intestine and modestly increases survival of mice exposed to infectious prions. Martin GR, Sharkey KA, Jirik FR. Scand J Gastroenterol. 2015 Jan 19:1-8. [Epub ahead of print] PMID: 25599123 AM841, a covalent cannabinoid ligand, powerfully slows gastrointestinal motility in normal and stressed mice in a peripherally-restricted manner. Keenan CM, Storr MA, Thakur GA, Wood JT, Wager-Miller J, Straiker A, Eno MR, Nikas SP, Bashashati M, Hu H, Mackie K, Makriyannis A, Sharkey KA. Br J Pharmacol. 2015 Jan 9. doi: 10.1111/bph.13069. [Epub ahead of print] PMID: 25572435 A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome. Bowles, N.P., Karatsoreos, I.N., Li, X., Vemuri, V.K., Wood, J.A., Li, Z., Tamashiro K.L., Schwartz, G.J., Makriyannis, A.M., Kunos, G., Hillard, C.J., McEwen, B.S., Hill, M.N. Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):285-90. doi: 10.1073/pnas.1421420112. Epub 2014 Dec 22. PMID: 25535367 Neuronal expression of the intermediate conductance calcium-activated potassium channel KCa3.1 in the mammalian central nervous system. Turner, R.W., Kruskic, M., Teves, M., Sheidl-Yee, T., Hameed, S. and Zamponi, G.W. Eur. J. Physiology 467 (2), 311-328. (2015).PMID: 24797146