19-Jun-2003

Valina Dawson, PhD Dr. Valina L. Dawson has been a member of the Department of Neurology since 1994. She is Professor of Neurology, Neuroscience and Physiology. Her research interest is in cellular signaling resulting in neurotoxicity and neurodegeneration. In particular, she is examining models of stroke, ischemic tolerance, and Parkinson's disease. These mechanisms are investigated by applying a multidisciplinary approach using primary tissue culture, molecular cloning strategies, transgenic and knock-out animals and protein biochemistry strategies. These research efforts have focused on the novel signaling pathways of nitric oxide such as poly(ADP-ribose) polymerase activation and the p21ras/MAPK signaling cascade. Dr. Dawson and her colleagues have found that poly(ADP-ribose) polymerase is important in both stroke and the animal model of Parkinson's Disease, the MPTP mouse model. To better understand the function of poly(ADP-ribose) polymerase in the brain, she has genetically engineered knockout mice and knock-in mice with mutations to different functional domains of PARP. She is also making transgenic and knockout mice to poly(ADP-ribose) glycohydrolase, the protein that degrades the ribose polymers. The p21ras/MAPK signaling cascade is critically important in ischemic tolerance and neuronal survival. Using strategies for functional genomics, she and her colleagues are investigating the gene products that mediate this neuroprotection. Identification of novel neuronal survival pathways will offer new therapeutic targets for the treatment of neurologic disease. Investigations are also underway to explore the utility of cell replacement and cell based therapies in experimental animal models of neurologic disease. Functional recovery following cell replacement is being assessed behaviorally, by imaging, neurochemistry and histology. These studies are integrated with ongoing investigations into neuronal death and survival pathways. The goal of this research is to ultimately apply the strategies and techniques identified and refined in the basic science laboratory to clinical treatment of neurologic disorders. CURRENT ADDRESS The Johns Hopkins Hospital Department of Neurology Carnegie 214 600 N. Wolfe Street Baltimore, MD 21287 Phone: 410-614-3359 Fax: 410-614-9568 E-Mail: vdawson@jhmi.edu EDUCATION & TRAINING 1983 B.S., Environmental Toxicology, University of California at Davis, Davis, CA 1989 Ph.D., Pharmacology, University of Utah School of Medicine, Salt Lake City, UT 1989-90 Fellowship, Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA 1990-93 Fellowship, Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD CERTIFICATIONS CURRENT APPOINTMENTS Professor of Neurology, The Johns Hopkins University School of Medicine Professor of Neuroscience, The Johns Hopkins University School of Medicine Professor of Physiology, The Johns Hopkins University School of Medicine Director, Neurobiology of Disease Program, Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD HONORS & AWARDS 1999 Mary Lou McIlhany Scholar 1999 International Society for Neurochemistry Young Investigator 1998 Staglin Music Festival Investigator 1996 American Heart Association Grant-in-Aid Award 1995 Muscular Dystrophy Association 1994 Alzheimer's Association Scholar Award 1994 NARSAD Young Investigator Award 1994 American Heart Association Grant-in-Aid Award 1994 AmFAR Scholar Award 1992 ADAMHA: Intramural Research Training Award 1992 National Institute on Drug Abuse Staff Fellow Award 1991 Winter Conference on Brain Research Fellowship 1990 National Institutes of Health: PRAT Fellowship RESEARCH ACTIVITIES Molecular mechanisms of neurodegeneration and regeneration Experimental models of stroke Gene discovery of novel cell survival pathways Cell based therapies for the treatment of neurologic disorders REPRESENTATIVE PUBLICATIONS Eliasson, M.J.L., K. Sampei, A.S. Mandir, P.D. Hurn, R.J. Traystman, J. Bao, A. Pieper, Z.-Q. Wang, T.M. Dawson, S.H. Snyder, and V.L. Dawson. "Poly(ADP-Ribose) Polymerase Gene Disruption Renders Mice Resistant to Cerebral Ischemia." Nature Med. 3: 1089-1095 (1997). Gonzalez-Zulueta, M., A.B. Feldman, L.J. Klesse, R.G. Kalb, J.F. Dillman, L.F. Parada, T.M. Dawson, V.L. Dawson. "Nitric Oxide Activation of p21ras//Erk-Dependent Signaling is Required for Ischemic Preconditioning in Neurons." Proc. Natl. Acad. Sci., USA., 97: 436-441 (2000). Mandir A.S, M. Poitras A.R. Berliner, W.J. Herring, D.B. Gustella, A. Feldman, G.G. Poirier, Z-Q. Wang, T.M. Dawson and V.L. Dawson. "NMDA but not Non-NMDA Excitotoxicity is Mediated by Poly (ADP-Ribose) Polymerase." J. Neurosci. 20:8005-8011 (2000). Sampei K., Mandir A.S., Asano Y., Wong P.C., Traystman R.J., Dawson V.L., Dawson T.M., Hurn P.D. "Stroke outcome in double-mutant antioxidant transgenic mice." Stroke 31:2685-2691 (2000). Dawson, V.L. and T.M. Dawson "Neuronal Ischaemic Preconditioning." Trends Pharmacol. Sci 21: 423-424 (2000). Chiavegatto, S., V.L. Dawson, L.A. Mamounas, VE. Koliatsos, T.M. Dawson, and R.J. Nelson. "Brain serotonin dysfunction accounts for aggression in male mice lacking neuronal nitric oxide synthase." Proc. Natl. Acad. Sci. USA, 98: 1277-1281, (2001). Nucifora F.C., Jr, M. Sasaki, M.F. Peters, H. Huang, J.K. Cooper, M. Yamada, H. Takahashi, S. Tsuji, J. Troncoso, V.L. Dawson, T.M. Dawson, C.A. Ross "Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity." Science 291: 2423-8 (2001).