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Adults (18-65), Geriatrics (65+)
Adults (18-65), Geriatrics (65+)
Recognized by Best Doctors in America 2005 - 2018
Recognized in Philadelphia Magazine's May 2002 Top Docs issue
Penn Neuroscience Center, Perelman Center for Advanced Medicine
South Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104
A facility of the Hospital of the University of Pennsylvania
RESEARCH INTERESTSNMDA receptors KEY WORDS:glutamate, receptor RESEARCH TECHNIQUESMolecular biology RESEARCH SUMMARYExcitotoxicity 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.
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 : 116462,2020.
Rummey, C., Farmer, J. M., Lynch, D. R.: Predictors of loss of ambulation in Friedreich's ataxia. EClinicalMedicine. 18 : 100213,2020.
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.
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.
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.
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): 571-575,2019.
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): 371,2019.
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-e124,2019.
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): 30109-7,2019.
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): 1594-1607,2019.
502 Abramson CenterChildren's Hospital of Philadelphia
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