Department of Neurology Home
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David R. Lynch, MD, PhD
Professor of Neurology
Department: Neurology
Contact information
502 Abramson Center
Children's Hospital of Philadelphia
Philadelphia, PA 19104
Children's Hospital of Philadelphia
Philadelphia, PA 19104
Office: 2155902242
Fax: 2155903779
Fax: 2155903779
Email:
LYNCHD@mail.MED.UPENN.EDU
LYNCHD@mail.MED.UPENN.EDU
Graduate Group Affiliations
Links
Pharmacological Sciences graduate group faculty webpage.
Neuroscience graduate group faculty webpage.
Pharmacological Sciences graduate group faculty webpage.
Neuroscience graduate group faculty webpage.
Education:
B.S. (Molecular Biophysics and Biochemistry)
Yale College, 1981.
Ph.D. (Neuroscience)
Johns Hopkins University, 1988.
M.D. (Neuroscience)
Johns Hopkins University, 1988.
B.S. (Molecular Biophysics and Biochemistry)
Yale College, 1981.
Ph.D. (Neuroscience)
Johns Hopkins University, 1988.
M.D. (Neuroscience)
Johns Hopkins University, 1988.
Post-Graduate Training
Intern in Internal Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, 1988-1989.
Resident in Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, 1989-1992.
Postdoctoral Fellowship, Departments of Pharmacology and Neurology, Clinical Specialties: Movement Disorders, Neurogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA , 1992-1995.
Intern in Internal Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, 1988-1989.
Resident in Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, 1989-1992.
Postdoctoral Fellowship, Departments of Pharmacology and Neurology, Clinical Specialties: Movement Disorders, Neurogenetics, University of Pennsylvania School of Medicine, Philadelphia, PA , 1992-1995.
Certifications
American Board of Psychiatry and Neurology, Certificate #38654, 1993.
Permanent linkAmerican Board of Psychiatry and Neurology, Certificate #38654, 1993.
Description of Research Expertise
RESEARCH INTERESTSNMDA receptors
KEY WORDS:
glutamate, receptor
RESEARCH TECHNIQUES
Molecular biology
RESEARCH SUMMARY
Excitotoxicity is a unique pathophysiological mechanism which is involved in cerebral ischemia, secondary damage in neuronal trauma, and neuronal damage from prolonged seizures. The deleterious effects from excitotoxicity result from calcium entry through a specific glutamate receptor, the N-methyl D-aspartate (NMDA) receptor. NMDA receptor antagonists act both as neuroprotective agents against excitotoxicity and as anticonvulsants in animals, but human clinical trials with the most potent agents have been complicated by side effects including psychosis. Much evidence indicates the presence of multiple types of NMDA receptors in the brain, and evidence from our laboratory suggests that different subtypes play different roles in physiological and excitotoxic processes. If one could develop therapeutic agents which are selective for the subtypes involved in excitotoxicity, one could more readily utilize NMDA receptor antagonists for treatment of human diseases.
We use a systematic approach to examine the subtype specific physiological and pharmacological properties of NMDA receptors. NMDA receptors are created in tissue culture expression systems, and their properties are studied biochemically, pharmacologically and physiologically to correlate receptor properties in these systems with such properties in vivo. We have previously shown that different NMDA receptor subtypes have distinct pharmacologies and produce different changes in intracellular calcium. In the near future we will extend these examinations of subtype specific properties to include the modulation of other intracellular messengers such as nitric oxide and examine the effect of such properties on excitotoxicity. Combined with our studies on the pharmacological specificity of NMDA receptor subtypes, this will facilitate the development of therapeutic agents directed to those NMDA receptors which play crucial roles in excitotoxicity.
Selected Publications
Madeline Snyder, Lauren Seyer, David R. Lynch, Andrew Resnick,Theresa A Zesiewicz : Cardiac Dysfunction Induced by Endocrinopathies in Friedreich’s Ataxia Journal of Child Neurology 2012 Notes: in press.Coppola G, Burnett R, Perlman S, Versano R, Gao F, Plasterer H, Rai M, Saccá F, Filla A, Lynch DR, Rusche JR, Gottesfeld JM, Pandolfo M, Geschwind DH. : A gene expression phenotype in lymphocytes from friedreich ataxia patients. Annals of Neurology 70(5): 790-804, November 2011.
Cook Denise R, Gleichman Amy J, Cross Stephanie A, Doshi Shachee, Ho Wenzhe, Jordan-Sciutto Kelly L, Lynch David R, Kolson Dennis L: NMDA Receptor Modulation by the Neuropeptide Apelin: Implications for Excitotoxic Injury. Journal of Neurochemistry 118(6): 1113-23, September 2011.
Tsou Amy Y, Paulsen Erin K, Lagedrost Sarah J, Perlman Susan L, Mathews Katherine D, Wilmot George R, Ravina Bernard, Koeppen Arnulf H, Lynch David R: Mortality in Friedreich Ataxia. Journal of the Neurological Sciences 307(1-2): 46-9, Aug 2011.
Meier Thomas, Perlman Susan L, Rummey Christian, Coppard Nicholas J, Lynch David R: Assessment of neurological efficacy of idebenone in pediatric patients with Friedreich's ataxia: data from a 6-month controlled study followed by a 12-month open-label extension study. Journal of Neurology Jul 2011.
Lagedrost Sarah J, Sutton Martin St John, Cohen Meryl S, Satou Gary M, Kaufman Beth D, Perlman Susan L, Rummey Christian, Meier Thomas, Lynch David R: Idebenone in Friedreich ataxia cardiomyopathy-results from a 6-month phase III study (IONIA). American Heart Journal 161(3): 639-645.e1, Mar 2011.
Selak Mary A, Lyver Elise, Micklow Elizabeth, Deutsch Eric C, Onder Ozlem, Selamoglu Nur, Yager Claire, Knight Simon, Carroll Martin, Daldal Fevzi, Dancis Andrew, Lynch David R, Sarry Jean-Emmanuel: Blood cells from Friedreich ataxia patients harbor frataxin deficiency without a loss of mitochondrial function. Mitochondrion 11(2): 342-50, Mar 2011.
Regner SR, Lagedrost SJ, Plappert T, Paulsen EK, Friedman LS, Snyder ML, Perlman SL, Mathews KD, Wilmot GR, Schadt KA, Sutton MS, Lynch DR: Analysis of Echocardiograms in a Large Heterogeneous Cohort of Patients With Friedreich Ataxia. American Journal of Cardiology 2011 Notes: in press.
Hsien-Yang Lee; Yong Huang; Nadine Bruneau; Patrice Roll; Elisha D.O. Roberson; Mark Hermann; Emily Quinn; James Maas; Robert Edwards; Tetsuo Ashizawa; Betul Baykan; Kailash Bhatia; Susan Bressman; Michiko K Bruno; Ewout R Brunt; Roberto Caraballo; Bernard Echenne; Natalio Fejerman; Steve Frucht; Christina A Gurnett; Edouard Hirsch; Henry Houlden; Joseph Jankovic; Wei-Ling Lee; David R Lynch; Shehla Mohamed; Ulrich Müller; Mark P Nespeca; David Renner; Jacques Rochette; Gabrielle Rudolf; Shinji Saiki; Bing-Wen Soong; Kathryn J Swoboda; Sam Tucker; Nicholas Wood; Michael Hanna; Anne Bowcock; Pierre Szepetowski; Ying-Hui Fu;Louis Ptacek: Mutations in the novel protein PRRT2 cause paroxysmal kinesigenic dyskinesia with infantileconvulsions. Cell Reports 2011 Notes: in press.
Singh P, Doshi S, Spaethling JM, Hockenberry AJ, Patel TP, Geddes-Klein DM, Lynch DR, Meaney DF. : NMDA receptor mechanosensitivity is governed by the C-terminus of the NR2B subunit. Journal of Biological Chemistry 2011.
