Frank Sharp, M.D.

Professor, Department of Neurology, School of Medicine

UC Davis M.I.N.D. Institute
2825 50th Street
Sacramento, CA 95817
E-mail:  frank.sharp@ucdmc.ucdavis.edu      

An internationally renowned clinical neurologist and neuroscientist, Dr. Sharp joined the UC Davis and M.I.N.D. Institute faculty in June 2004. Research in his laboratory focuses on molecular neurobiology, genomics, neural cell injury and cell death and the blood genomics of neurological disease. Prior to his appointment at UC Davis, Dr. Sharp had a distinguished clinical and research career at UC San Diego, UC San Francisco and the University of Cincinnati, making groundbreaking contributions to new fields of study and new insights into brain function and disease. Among these contributions were: first laboratory to show proof of principle for using blood genomics to detect pathological events in the animal and human brain, paved the way for performing PET and fMRI studies in humans, and first to demonstrate that a transcription factor can be used to map active neurons. Dr. Sharp is currently on the editorial boards of several journals, has been a standing member of the AHA Brain grant review committee, and is a permanent member of the NINDS NSDA review Committee.

B.S. University of California, Davis, 1968
M.D. University of San Diego, 1972

Tang Y, Glauser TA, Gilbert D, Hershey A, Sharp FR.  Blood genomic profiles of Valproic Acid treatment and its anticonvulsant efficacy.  Acta Neurologica Scandinavica 109(3):159-168, 2004.This pilot study demonstrates that genomic profiles obtained with microarrays from the blood of children with epilepsy are different from those of normal children. Treatment with the anti-convulsants valproic acid and carbamazepine produced unique blood genomic profiles. The blood genomic profile for valproic acid in the children who responded to therapy was different from that in the children who did not respond to therapy. This study lays the ground work  for distinguishing various neurodevelopmental disorders including autism on the basis of a blood genomic profile, and offers hope that treatment options might be based upon gene expression profiles in the blood.

Chang EF, Wong RJ, Vreman JH, Igarashi T, Galo E, Sharp FR, Stevenson DK, and Noble-Haeusslein LJ (2003) Heme oxygenase-2 protects against lipid peroxidation-mediated cell loss and impaired motor recovery after traumatic brain injury, Journal of Neuroscience, 23 (9): 3689-3697. This study shows that the heme oxygenase-2 protein protects injured brain, and is relevant to acute traumatic injury and neurodevelopmental disorders.

Ran R, Zhou G, Lu A, Tang Y, Rigby AC, Vaux DL, and Sharp FR (2004) Hsp70 impairs NF-kappa B signaling and promotes TNF-alpha-mediated apoptosis, Genes and Development, 18 (12) 1466-1481.   This study shows that the co-expression of the cytokine TNF and heat shock proteins leads to cell death in developing cells and in cancer cells. This is a major study showing that apoptosis induced via the extrinsic-death receptor pathway is augmented by the heat shock stress response, and this would have tremendous implications for cell death during development in the brain. 

Hypoxia Induced Tolerance to Cerebral Ischemi,a Symposium Speaker, International Cerebral Blood Flow and Metabolism Society Meeting, Calgary, Canada,  July 2003.

Genomics of Neurological Disease, Invited Speaker, Case Western Reserve University, Cleveland, Ohio, 2003.

Blood Genomics of Pediatric Neurological Diseases, Invited Speaker, Neuroscience Seminar Series, University of North Carolina, Chapel Hill, NC, 2003.

Blood Genomics of Stroke and other Neurological Diseases, Invited Speaker, Merck, San Diego, CA, July 2003.

Blood Genomics of Neurological Disease, Invited Speaker, Grand Rounds, University of California at San Diego. LaJolla, CA, 2004.

Heat Shock Protein Control of Apoptosis in the Brain, Invited Speaker, International Pharmacology of Cerebral Ischemia Meeting, Marburg, Germany, 2004.

Molecular Definition of the Ischemia Penumbra, Invited Speaker, Princeton Stroke Conference, Baltimore, MD, 2004.

Hypoxia Induced Tolerance in the Brain, Invited Speaker, Hershey Neonatal Cerebral Ischemia Meeting, Asilomar, CA, 2004.

Principal Investigator: Neuronal Injury and Blood Genomics, NINDS, 6/02-5/06, $230,000 annual direct. The major goal of this project is to objectively differentiate seizures, syncope, global cerebral ischemia, hypoglycemia, and transient ischemic attacks hours to days after they occur; and to begin to identify blood genomic markers of neuronal death associated with acute neurological diseases that might also be useful in chronic neurological diseases.

Principal Investigator: Neurotoxicity of NMDA Receptor Antagonists, NIMH, 9/02-7/06, $210,000 annual direct.  The major goal of this project is to define the circuits that mediate the cortical injury produced by NMDA receptor antagonists in animals and may help define circuits and transmitters that mediate psychosis in people.

Principal Investigator: Recanalization Therapies and Markers of Stroke (Project 3), NINDS, 9/02-8/07, $30,000 annual direct. The long-term goal of this program project grant (an application to the SPOTRIAS program – Specialized Program of Translational Research in Acute Stroke) is to improve the early recanalization of occluded arteries in patients with acute ischemic stroke without compromising safety through the development of new recanalization strategies and markers of outcomes and risk

Principal Investigator: Markers of CNS Injury, NINDS, 6/03-6/05, $230,000 annual direct. The aim of this project is to show that heat shock proteins can protect the ischemic brain, and specifically will test whether recombinant PTD-Hsp70 proteins or a drug that induces heat shock proteins show potential for the treatment of stroke. 

Principal Investigator (subcontract): Blood Genomics of Anticonvulsant Efficacy, NINDS, 7/03-3/07, $30,000 annual direct.  The aim of this project is to determine if there is a blood genomic pattern that is predictive of hematological toxicity of anticonvulsants.

Principal Investigator (subcontract): Blood Genomics of Pediatric Headache, NINDS, 4/03-3/07, $70,000 annual direct. The aims of this project are to determine whether acute migraine and chronic daily headache patients have similar or different blood genomic profiles, and whether there is a different blood genomic profile in patients that respond to NSAIDs compared to those patients that require triptans as rescue medication.

Editorial Board, Molecular Brain Research, Brain Research
Editorial Board, Journal of Cerebral Blood Flow and Metabolism
Editorial Board, Journal of Neurochemistry
Member, NINDS NSDA Study Section
Ad Hoc Reviewer, NINDS BCDN-3 Study Section
Intramural Reviewer, NINDS Stroke Laboratory
Intramural Reviewer, NIMH Cerebral Injury Laboratory
Reviewer for the following journals: Science, Nature, Journal of Neuroscience, Proceedings National Academy of Sciences, European Journal of Neuroscience, Journal of Comparative Neurology, Journal of Neuroscience Research, Brain Research, Molecular Brain Research, Developmental Brain Research, Experimental Neurology, Neuroscience, Annals of Neurology, Archives of Neurology, Neurology