Penn Comprehensive Neuroscience Center

Faculty Members
faculty photo

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
Graduate Group Affiliations
Education:
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.
Certifications
American Board of Psychiatry and Neurology, Certificate #38654, 1993.
Permanent link
 
> Perelman School of Medicine   > Faculty   > Details

Description of Research Expertise

RESEARCH INTERESTS
NMDA 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

St John Sutton, M., Ky, B., Regner, S.R., Schadt, K.M., Plappert, T., He, J., D’Souza, B. , Lynch, D.R. : Longitudinal Strain in Friedreich Ataxia: A Potential Marker for Early Left Ventricular Dysfunction Echocardiography 31(1): 50-7, Jan 2014.

Delatycki,M.B.,Tai, G., Corben, L.,Yiu, E.M. ,Evans-Galea, M. V , Stephenson,S., Gurrin, L., Allen, K. J., Lynch, D. R., Lockhart, P.J.: HFE p.C282Y heterozygosity is associated with earlier disease onset in Friedreich ataxia. Movement Disorders 2014 Notes: in press.

Gleichman, A.L., Panzer, J. A., Baumann, B., Dalmau, J., Lynch, D. R.: Antigenic and mechanistic characterization of anti-AMPA receptor encephalitis. Annals of Clinical and Translational Neurology 2014 Notes: in press.

Nathaniel R. Greeley, Sean Regner, Steve Willi, David R. Lynch: Cross-sectional analysis of glucose metabolism in Friedreich Ataxia Journal of the Neurological Sciences 2014 Notes: in press.

Eric C. Deutsch,Devin Oglesbee, Nathaniel R. Greeley, David R. Lynch : Utility of Frataxin Immunoassays for the diagnosis of Friedreich Ataxia. Journal of Neurology, Neurosurgery and Psychiatry 2014 Notes: in press.

Lin, H., Hsu,F-C, Baumann, B. H., Coulter, D. A., Lynch, D. R.: Cortical synaptic NMDA receptor deficits in alpha7 nicotinic acetylcholine receptor gene deletion models: Implications for neuropsychiatric diseases Neurobiology of Disease 2014 Notes: in press.

Friedman, L.S., Schadt, K.A., Regner, S.R., Mark, G.E., Lin, K.Y., Sciascia, T., St John Sutton, M., Willi, S., Lynch, D.R.: Elevation of Serum Cardiac Troponin I in a Cross-Sectional Cohort of Asymptomatic Subjects with Friedreich Ataxia International Journal of Cardiology 167(4): 1622-4, Aug 2013

Gresa-Arribas, N., Titulaer, M.J., Torrents, A., Aguilar, E., McCracken, L. Leypoldt, F., Gleichman, A. J., Balice-Gordon, R., Rosenfeld, M.R., Lynch, D.R., Graus, F., Dalmau, J.: Diagnosis and significance of antibody titers in anti-NMDA receptor encephalitis, a retrospective study. Lancet Neurology 4422(13): 70282-5. Dec 2013.

Sankha S. Basu, Eric C. Deutsch, Alec Schmaier, David R. Lynch, and Ian A. Blair: Human platelets as a platform to monitor metabolic biomarkers using stable isotopes and liquid chromatography-mass spectrometry. Bioanalysis 5(24): 3009-21. Dec 2013.

Devin Oglesbee; Charles Kroll, Oleksandr Gakh, Eric C. Deutsch, David R. Lynch, Ralitza Gavrilova, Silvia Tortorelli, Kimiyo Raymond, Dimitar Gavrilov, Piero Rinaldo, Dietrich Matern, and Grazia Isaya, : A High-Throughput Immunoassay for the Biochemical Diagnosis of Friedreich Ataxia in Dried Blood Spots and Whole Blood Clinical Chemistry 59(10): 1461-9, Oct 2013.

back to top
Last updated: 04/22/2014
The Trustees of the University of Pennsylvania