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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
Office: 2155902242
Fax: 2155903779
Lab: 2155901451
Graduate Group Affiliations
B.S. (Molecular Biophysics and Biochemistry)
Yale College, 1981.
M.D. (Neuroscience)
Johns Hopkins University, 1988.
Ph.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.
American Board of Psychiatry and Neurology, Certificate #38654, 1993.
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Description of Research Expertise

NMDA receptors

glutamate, receptor

Molecular biology

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

Lynch DR, et al.: Randomized, Double-Blind, Placebo-Controlled Study of Interferon- γ1b in Friedreich Ataxia. Annals of Clinical and Translational Neurology 2019 Notes: in press.

Clark, E., Schadt, K., Strawser, C., Lynch, D. R.: Identification of a Novel Missense Mutation in Friedreich’s Ataxia –FXNW168R. Annals Clin Translational Neurol 2019 Notes: in press.

Puligedda, R. , Devi, C., Fetwehal, S, Uvaru, L, Kouiavskaia, D, Chumakov, K, Lynch, D, Prend, G, Kaushik, R. , Dessain : Capture and display of antibodies secreted by hybridoma cells enables fluorescent on-cell screening. Monoclonal Antibodes 2019 Notes: in press.

Dong, Y, Mcmillan E, Clark E, Lin H, Lynch DR: GRP75 overexpression rescues frataxin deficiency and mitochondrial phenotypes in Friedreich Ataxia cellular models. Human Mol Genet 2019 Notes: in press.

Nachun, D., Gao, F., Isaacs, C., Strawser, C., Yang, Z., Dokuru, D., Van Berlo, V., Sears, R,, Farmer, J., Perlman, S., Lynch, D.R., Coppola, G.: Peripheral blood gene expression reveals an inflammatory transcriptomic signature in Friedreich’s ataxia patients. Hum Molec Genet 27(17): 2965-2977, Sep 2018 Notes: in press.

Zesiewicz, T., Salemi, J.L., Perlman, S., Sullivan, K. L., Shaw, J. D. Huang, Y.,Isaacs, C., Gooch, C.,Lynch, D. R., Klein, M. B. : Double-blind, Randomized, Controlled Trial of EPI-743 in Friedreich’s Ataxia. Neurodegen Dis Management 8(4): 233-242. Aug 2018 Notes: in press.

Sharma, R.,Lee, M., Panzer, J., Lee, J. L .,Felicori, L. F.,Chandu, D., Rattelle, A., Ippolito, G., Cox, R., Lynch, D.R., Dessain, S,: Monoclonal antibodies from patients with anti-NMDA receptor encephalitis. Annals of Clinical and Translational Neurology 5(8): 935-951. Jul 2018.

Hamedani,A.G., Hauser, L., Perlman, S., Mathews, K., Wilmot, G.R, Zesiewicz, T.,Subramony, S.H.,Ashizawa, T., Delatycki, M., Brocht, A.,and Lynch, D. R.: Longitudinal analysis of contrast acuity in Friedreich ataxia. Neurol Genetics 4(4): e250. Jul 2018 Notes: in press.

Al-Saleem, F., Kaushik, R., Salovin, A.J., Lynch, D.R., Dessain, S.: Membrane-bound and soluble forms of an NMDA receptor extracellular domain retain epitopes targeted in auto-immune encephalitis. BMC Biotechnology 18.(1): 41, Jun 2018.

Ejaz, R., Chen, S., Isaacs, C. J., Carnevale, A., Wilson, J., George, K., Delatycki, M. B., Perlman, S. L. Mathews, K. D., Wilmot, G. R.,Hoyle, J. C., Subramony, S. H., Zesiewicz, T., Farmer, J. M., Lynch, D. R., Yoon, G. : Impact of mobility device use on quality of life in children with Friedreich ataxia. J Child Neurol 33(6): 397-404, May 2018.

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Last updated: 01/19/2019
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