David R. Lynch, MD, PhD

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Professor of Neurology
Department: Neurology
Graduate Group Affiliations

Contact information
502 Abramson Center
Children's Hospital of Philadelphia
Philadelphia, PA 19104
Office: 2155902242
Fax: 2155903779
Lab: 2155901451
B.S. (Molecular Biophysics and Biochemistry)
Yale College, 1981.
Ph.D. (Neuroscience)
Johns Hopkins University, 1988.
M.D. (Neuroscience)
Johns Hopkins University, 1988.
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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

Xiong, E., Lynch, A. E., Corben, L. A., Delatycki, M. B., Subramony, S. H., Bushara, K., Gomez, C. M., Hoyle, J. C., Yoon, G,, Ravina, B., Mathews, K. D., Wilmot, G., Zesiewicz, T., Perlman, S. L., Farmer, J. M., Rummey, C., Lynch, D. R. : Health related quality of life in Friedreich Ataxia in a large heterogeneous cohort. J Neurol Sci. 410: 116462, Mar 2020.

Rummey, C., Farmer, J. M., Lynch, D. R.: Predictors of loss of ambulation in Friedreich's ataxia. EClinicalMedicine. 18: 100213, Jan 2020.

Misiorek, J. O., Schreiber, A. M., Urbanek-Trzeciak, M. O., Jazurek-Ciesiołka, M., Hauser, L. A., Lynch, D. R., Napierala, J. S., Napierala, M.: A comprehensive transcriptome analysis identifies FXN and BDNF as novel targets of miRNAs in Friedreich’s ataxia patients. Mol Neurobio 2020 Notes: in press.

Afsharian, P., Nolan-Kenney,R., Lynch, A. E., Balcer, L. J., Lynch, D. R.: Correlation of visual quality of life with clinical and visual status in Friedreich ataxia. Journal of Neuroophthalmology 2020 Notes: in press.

Alexandra Clay, Kristin M Obrochta, Russell K Soon Jr, Christopher B Russell, and David R Lynch : Neurofilament Light Chain as a potential biomarker of disease status in Friedreich Ataxia Journal of Neurology 2020 Notes: in press.

Patel, M., Schadt, K., McCormick, A., Isaacs, C., Dong, Y. N., Lynch, D. R.: Open label Pilot Study of Oral Methylprednisolone for the Treatment of Patients with Friedreich Ataxia. Muscle Nerve 60(5): 571-575, Nov 2019.

Rummey, C., Corben, L., Delatycki, M., Subramony, S. H., Bushara, K.O., Gomez, C., Hoyle, J. C., Yoon, G., Ravina, B., Mathews, K. D., Wilmot, G. R., Zesiewicz, T. A., Perlman, S. L., Farmer, J. M., Lynch, D. R.: Psychometric Properties of the Friedreich Ataxia Rating Scale. Neurology Genetics 5(6): 371, Oct 2019.

Marty, B., Naeije, G., Bourguignon, M., Wens, V., Jousmäki, V., Lynch, D. R., Gaetz, W., Goldman, S., Hari, R., Pandolfo, M., De Tiège, X.: Evidence for genetically determined degeneration of proprioceptive tracts in Friedreich ataxia. Neurology 93(2): e116-e124, Jul 2019.

Weng. L., Wang, Q., Yu, S., Yang, X., Lynch, D. R., Mesarosa, C., Blair, I. A.: Evaluation of Antibodies for Western Blot Analysis of Frataxin Protein Isoforms. Journal of Immunological Methods S0022-1759(19): 30109-7, Jul 2019.

Dong, Y., Mcmillan, E., Clark, E., Lin, H., Lynch, D. R.: GRP75 overexpression rescues frataxin deficiency and mitochondrial phenotypes in Friedreich Ataxia cellular models. Human Mol Genet 28(10): 1594-1607, May 2019.

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Last updated: 04/29/2020
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