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Personal History
Professor of Neurosurgery, Pathology and Physiology at the University of Maryland School of Medicine, Dr. Simard received his M.D., Ph.D. from Creighton University in 1980 and completed his residency training in neurosurgery at the University of Florida.
In 1983, he worked with Professor Hans Meves as a post-doctoral fellow at the Physiologisches Institut at the Universitat des Saarlandes in Germany. A board-certified neurosurgeon, Dr. Simard specializes in the treatment of brain tumors, stroke, and related diorders with special emphasis on carotid endarterectomy, aneurysm, and arteriovenous malformations treated by advanced microsurgical techniques and by Gamma Knife. He serves as Chief of Neurological Surgery at the Baltimore Veterans' Affairs Medical Center.
Research Interests
As Director of the Department's Cerebrovascular Research Laboratory, Dr. Simard studies cellular mechanisms regulating cerebral blood flow. A primary focus of this research involves patch clamp study of ion channel function in cerebral smooth muscle. The patch clamp, an exquisitely sensitive method for testing and recording cellular electrical currents, has been employed in the lab's recent investigations of calcium and potassium channels in smooth muscle cells from the basilar artery and in PC12 cells.
Dr. Simard has also recently published findings on early signaling events by endotoxin in neuronal cells and is currently studying ion channel function and regulation in astrocytes activated by injury to the central nervous system. The laboratory's work is funded by grants from the National Institutes of Health, the American Heart Association, and the University of Maryland School of Medicine. Dr. Simard has been an NIH-funded researcher for eight years and serves on the Neurology Advisory Panel of the National Institutes of Health. He has directed the work of several doctoral students.
Publications
Book Chapters
Watt DD, Simard JM, Babin DR, Mlejnek RV. Physiological characterization of toxins isolated from scorpion venom. In: Rosenberg P, ed. Toxins: Animal, Plant, and Microbial. Oxford: Permagon Press, 1978, Ch. 13, pp. 109-116
Simard JM, Watt DD. Venoms and Toxins. In: Polis, G., ed. Biology of scorpions. Stanford University Press, 1989, Ch. 10, pp. 414-444
Numaguchi Y, Clouston JE, Zoarski GH, Aldrich EF, Simard JM, Zagardo MT, Aldrich C. Intra-arterial Papaverine Treatment for Cerebral Vasospasm. In: Cerebrospinal Vascular Diseases. Tamaki N (Ed), Springer-Verlag Tokyo, 1994, Ch. 9, pp. 153-160.
Selected Publications
Perillan, PR, Chen M, Potts EA, Simard JM. TGFbeta1 Regulates Kir2.3 inward rectifier K+ channels via phospholipase C and protein kinase C-delta in reactive astrocytes from adult rat brain. J. Biol Chem 277(3): 1974-1980, 2002.
Ioffe V, Hudes RS, Shepard, D, Simard JM, Chin LS, Yu C. Fetal and ovarian radiation dose in patients undergoing gamma knife radiosurgery. Surgical Neurology, 58(1): 32-41, 2002.
Li X., Simard JM. Increase in Cx45 gap junction channels in cerebral smooth muscle cells from SHR. Hypertension, 40: 940-946, 2002.
West GA, Meno JR, Nguyen TS, Ngai AC, Simard JM, Winn HR. cGMP-dependent and not cAMP-dependent kinase is required for adenosine induced dilation of intracerebral arterioles. J Cardiovasc Pharmacol, 41(3):444-51, 2003.
Dalton S, Gerzanich V, Chen M, Shuba Y, Simard JM. Chlorotoxin-sensitive Ca2+ -activated C1- channel in type R2 reactive astrocytes from adult rat brain. GLIA, 42(4): 325-339, 2003.
Gerzanich V, Ivanova S, Zhou H, Simard, JM. Mislocalization of eNOS and upregulation of cerebral vascular Ca2+ channel activity in angiotensin-hypertension. Hypertension, 41: 1124-1130, 2003.
Murphy K, Gerzanich V, Zhou H, Ivanova S, Dong Y, Hoffman G, West GA, Winn HR, Simard JM. Adenosine-A2a receptor down-regulates cerebral smooth muscle L-type Ca2+ channel activity via protein tyrosine phosphatase, not cAMP-dependent protein kinase. Mol Pharmacol, 64(3):640-9, 2003.
Ma L, Chin LS, DiBiase SJ, Gullapalli R, Kennedy A, Simard JM, Slawson R. Concomitant boost of stratified target area with gamma knife radiosurgery: a treatment planning study. Am J Clin Oncol, 26(4):E100-5, 2003.
Simard JM, Kent TA. Vascular smooth muscle proliferation as a target for therapeutic intervention. Stroke, 34(8):ee108; author reply e108, 2003.
Chen M, Dong Y, Simard JM. Functional coupling between sulfonylurea receptor type 1 and a non-selective cation channel in reactive astrocytes from adult rat brain. J Neuroscience, 23(24):8568-77, 2003.
Gerzanich V, Ivanova S, van der Heiden M, Zhou H, Simard JM. Trans-cellular PCNA gene activation in cerebral vascular smooth muscle by endothelial oxidative injury in vivo. Arterioscler Thromb Vasc Biol, 23(11):2048-54, 2003.
Gerzanich V, Ivanov A, Ivanova S, Yang JB, Zhou H, Dong Y, Simard JM. Alternative splicing of cGMP-dependent protein kinase I in angiotensin-hypertension: novel mechanism for nitrate tolerance in vascular smooth muscle. Circ Res, 93(9):805-12, 2003.
Rama Rao KV, Chen M, Simard JM, Norenberg MD. Suppression of ammonia-induced astrocyte swelling by cyclosporin A. J Neurosci Res, 74(6):891-7, 2003.
Rama Rao KV, Chen M, Simard JM, Norenberg MD. Increased aquaporin-4 expression in ammonia-treated cultured astrocytes. Neuroreport, 14(18):2379-82, 2003.
Ivanov A, Ivanova S, Melnitchenko L, Gerzanich V, Shuba M, Simard JM. PCNA upregulation in cerebral vessels with angiotensin II – hypertension: abnormal regulation of Ca2+ channel and nitrate tolerance associated with alternative splicing of cGKI. Neurophysiology, 35(3/4): 209-14, 2003.
Gerzanich V, Ivanova S, Simard JM. Early pathophysiological changes in cerebral vessels predisposing to stroke. Clin Hemorheol Microcirc, 29(3-4):291-4, 2003.
Simard JM, Chen M. Regulation by sulfonylurea receptor type 1 of a non-selective cation channel involved in cytotoxic edema of reactive astrocytes. J Neurosurg Anesthesiol, 16(1):98-9, 2004.
Ma L, Kwok Y, Chin LS, Simard JM, Regine WF. Concomitant GRID boost for Gamma Knife radiosurgery. Med Phys, 32(11):3419-23, 2005.
Ivanov A, Gerzanich V, Ivanova, S, DenHaese, R, Tsymbalyuk, O, Simard JM. Adenylate cyclase 5 and KCa1.1 channel are required for EGFR up-regulation of PCNA in native contractile rat basilar artery smooth muscle. J Physiol, 570.1:73-84, 2006.
Simard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchenko L, Tsymbalyuk N, West GA, Gerzanich V. Newly expressed SUR1-regulated NC Ca-ATP channel mediates cerebral edema after ischemic stroke. Nature Medicine, 12(4):433-40, 2006.
Sun Y, Chen M, Lowentritt BH, Van Zijl PS, Koch KR, Keay S, Simard JM, Chai TC. EGF and HB-EGF Modulate Inward Potassium Current in Human Bladder Urothelial Cells from Normal and Interstitial Cystitis Patients. Am J Physiol Cell Physiol, 292(1):C106-114, 2006.
Qin K, Zhao L, Tang Y, Bhatta S, Simard JM, Zhao RY. Doppel-induced apoptosis and counteraction by cellular prion protein in neuroblastoma and astrocytes. Neuroscience, 141(3):1375-1388, 2006.
Simard JM, Gerzanich V. Sphingolipids and transient receptor potential channels: evolutionarily ancient families now joined. Circ Res, 98(11):1347-8, 2006.
Iadecola C, Goldman SS, Harder DR, Heistad DD, Katusic ZS, Moskowitz MA, Simard JM, Sloan MA, Traystman RJ, Velletri PA. Recommendations of the National Heart, Lung, and Blood Institute working group on cerebrovascular biology and disease. Stroke. 37(6):1578-81, 2006.
Simard JM, Kent TA, Chen, M, Tarasov K, Gerzanich V. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurology, 6:258-268, 2007.
Yurovsky VV, Gerzanich V, Ivanova S, Dong Y, Tsymbalyuk O, Simard JM. Autocrine TGFβ1 mediates Angiotensin II-induced proliferative response of cerebral vessels in vivo. American Journal of Hypertension, 20(9):950-956, 2007.
Simard JM, Tarasov K, Gerzanich V. Non-selective cation channels, transient receptor potential channels and ischemic stroke. Biochim Biophys Acta, Molecular Basis of Disease, 1772(8):947-957, 2007.
Kunte H, Schmidt S, Eliasziw M, del Zoppo GJ, Simard JM, Masuhr F, Weih M, Dirnagl U. Sulfonylureas improve outcome in patients with type 2 diabetes and acute ischemic stroke. Stroke, 38(9):2526-2530, 2007.
Liang D, Bhatta S, Gerzanich V, Simard JM. Cytotoxic edema: mechanisms of pathological cell swelling. Neurosurgical Focus, Brain edema, May 15;22(5):E2, Review, 2007.
Simard JM, Tsymbalyuk O, Ivanov A, Ivanova S, Bhatta S, Geng Z, Woo SK, Gerzanich V. Endothelial sulfonylurea receptor 1-regulated NCCa-ATP channels mediate progressive hemorrhagic necrosis following spinal cord injury. Journal of Clinical Investigation, 117(8);2105-2113, 2007.
Simard JM, Woo SK, Bhatta S, Gerzanich V. Drugs acting on SUR1 to treat CNS ischemia and trauma. Current Opinion Pharmacol, 8(1):42-49, 2008.
Lumpkins K, Bochicchio GV, Zagol B, Ulloa K, Simard JM, Schaub S, Meyer W, Scalea T. Plasma levels of the beta chemokine regulated upon activation, normal T cell expressed, and secreted (RANTES) correlate with severe brain injury. J. Trauma, 64(2):358-361, 2008.
Simard JM, Geng, Z, Woo SK, Ivanova S, Tosun C, Melnichenko L, Gerzanich V. Glibenclamide reduces inflammation, vasogenic edema, and caspase-3, activation after subarachnoid hemorrhage. Journal of Cerebral Blood Flow & Metabolism, 29(2):317-330, 2008.
Simard JM, Castellani RJ, Ivanova S, Koltz MT, Gerzanich V. Sulfonylurea receptor 1 in the germinal matrix of premature infants. Pediatric Research, 64(6):648-652, 2008.
Lumpkins KM, Bochicchio GV, Keledjian K, Simard JM, McCunn M, Scalea T. Glial fibrillary acidic protein is highly correlated with brain injury. J. Trauma, 65(4):778-782, 2008.
Simard JM, Yurovsky V, Tsymbalyuk N, Melnichenko L, Ivanova S, Gerzanich V. Protective effect of delayed treatment with low-dose glibenclamide in three models of ischemic stroke. Stroke, 40(2):604-609, 2008.
Gerzanich V, Woo K, Vennekens R, Tsymbalyuk O, Ivanova S, Ivanov A, Geng Z, Chen Z, Nilius B, Flockerzi V, Freichel M. and Simard JM. De novo expression of TRPM4 initiates secondary hemorrhage in spinal cord injury. Nature Medicine, 15(2):185-191, 2009.
Kahle K, Gerzanich V, Simard JM. Molecular mechanisms of microvascular failure in CNS injury – synergistic roles of NKCC1 and SUR1/TRPM4. J Neurosurgery, in press, 2009.
Aarabi B, Hesdorffer DC, Simard JM, Ahn ES, Aresco C, Eisenberg HM, McCunn M, Scalea T. Comparative study of decompressive craniectomy after mass lesion evacuation in severe head injury. Neurosurgery, 64(5):927-940, 2009.
Simard JM, Kilbourne M, Tsymbalyuk O, Tosun C, Caridi J, Ivanova S, Bochicchio G, Gerzanich V. Key role of sulfonylurea receptor 1 in progressive secondary hemorrhage following brain contusion. J Neurotrauma, Epub ahead of print, 2009.
Kahle KT, Simard JM, Staley KJ, Nahed BV, Jones PS, Sun D. Molecular mechanisms of ischemic cerebral edema: role of electroneutral ion transport. Physiology, 24:257-265, 2009.
Aarabi BA, Simard JM. Traumatic brain injury. Curr Opin Crit Care, 15(6):548-553, 2009.
Li M, Sun Y, Simard JM, Wang JY, Chai TC. Augmented bladder urothelial polyamine signaling and block of BK-channel in the pathophysiology of overactive bladder syndrome. Am J Physiol Cell Physiol, Epub ahead of print, 2009.