Valina Dawson, PhD

Highlights

Languages

English

Gender

Female

Johns Hopkins Affiliations:

Johns Hopkins School of Medicine Faculty

About Valina Dawson

Professional Titles

Director, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,

Primary Academic Title

Professor of Neurology

Background

Valina L. Dawson, PhD, is a Professor of Neurology, Neuroscience, Physiology and the Graduate Program in Cellular & Molecular Medicine. She is co-director of the Neuroregeneration and Stem Cell Programs in the Institute for Cell Engineering. Dr. Dawson’s laboratory is actively engaged in discovering and defining cell signaling pathways that lead to either neuronal survival or neuronal death. We have characterized neuronal injury and survival pathways in cell, fly and mouse models of Parkinson’s disease and stroke. She explores the role of the monogenic forms of Parkinson’s disease with a focus on parkin, EIF4G1 and LRRK2 in order to begin to define the biochemical signaling important to Parkinson’s disease. She has developed yeast, cellular, fly and mouse models to explore the Parkinson’s disease causing mutations as well as studying human neuronal cultures and human postmortem tissue explore survival and disease signaling events relevant to Parkinson’s disease. and stroke as well as to define neuron survival networks.

Dr. Dawson’s laboratory in studying mechanisms of brain cell death in stroke, has defined the excitotoxic signaling pathway mediated by nitric oxide, poly(ADP-Ribose) polymerase and apoptosis inducing factor and named it Parthanatos, to distinguish it from other distinct forms of cell death including apoptosis, autophagy and necrosis. She has identified and characterized new survival molecules which include a transcription factor NFIA, a novel E3 ligase Iduna, a novel Notch regulatory protein Botch and a novel AAA+ ATPase Thorase that acts to disassemble the GRIP1/GluR2 complex, thus regulating excitability, plasticity and behavior, as well as a microRNA, mIR-223 that regulates neuronal survival in part through regulation of glutamate receptor expression. Recently we have found overlap between our investigations in Parthanatos and Parkinson’s disease in that age dependent loss of dopamine neurons due to expression of the parkin substrate AIMP2 is dependent on Parthanatos. She is currently exploring if Parthanatos generally contributes to DA neurodegeneration and PD and has exciting new preliminary data that Parthantos is a common feature in many PD models as well as in human PD postmortem tissue.

The Dawson laboratory employs advanced technologies in high throughput screening, next generation sequencing including RNA Seq and ChIP Seq, ribosomal foot printing, and high throughput proteomic analysis coupled with advanced computational biology to investigate signaling networks important in stroke, Parkinson’s disease and other neurodegenerative disorders. The overarching goal of the research is to understand death and survival signaling in order to identify new targets for therapeutic development.

Additional Academic Titles

Professor of Neuroscience, Professor of Physiology

Contact for Research Inquiries

Phone: (410) 614-3361
vdawson@jhmi.edu

Research Interests

Neuronal cell death, Neuronal cell survival, Neuronal stem cell development, Parkinson's disease

Research Summary

The Dawson lab studies neuronal cell death and survival, the molecular underpinnings of Parkinson’s disease (PD) and the development of neuronal stem cells. The lab has named a new cell death process Parthanatos. In the brain, Parthanatos is important in ischemic and excitotoxic injury and in models of Parkinson’s disease. The cell death mechanism involves nuclear activation of poly(ADP-ribose) polymerase and mitochondrial release of apoptosis inducing factor in the integration of the death signal; current research aims to further understand how this pathway works. In addition to cell death, the team also strives to understand how cells survive by characterizing survival genes and proteins involved in preconditioning. The team uses induced pluripotent stem cells to identify pharmaceutical agents that might be used therapeutically to protect the brain.

To understand the role of LRRK2 in the function and dysfunction of neurons and in Parkinson’s disease, the team has generated LRRK2 knockout mice and LRRK2 transgenic mice and human dopaminergic cultures from reprogrammed patient fibroblasts to identify and characterize the interaction of LRRK2 and its protein targets through state-of-the art protein biochemistry with the hope of finding new strategies to treat PD.

Google Scholar

http://scholar.google.com/citations?hl=en&user=JS3_-uoAAAAJ&view_op=list_works&gmla=AJsN-F6O3FuIAdRzZB9lKnEn5aLn63BvTfPf59c7acZ4ix_3lG5c2B2o6zWVQTK7wdcOa7AUORMvzt1XJ9Pz69ZCFXHrIvsWz6kbvZn84mfO8FaWU9VtMZuCySeil423CBjyXg1liHQd

PubMed

http://www.ncbi.nlm.nih.gov/pubmed?term=Dawson%20VL%5BAuthor%5D&cauthor=true&cauthor_uid=24843043

Selected Publications

Botch Is a γ-Glutamyl Cyclotransferase that Deglycinates and Antagonizes Notch. Chi Z, Byrne ST, Dolinko A, Harraz MM, Kim MS, Umanah G, Zhong J, Chen R, Zhang J, Xu J, Chen L, Pandey A, Dawson TM, Dawson VL. Cell Rep. 2014 May 8;7(3):681-8. doi: 10.1016/j.celrep.2014.03.048. Epub 2014 Apr 24. PMID: 24767995
Msp1/ATAD1 maintains mitochondrial function by facilitating the degradation of mislocalized tail-anchored proteins. Chen YC, Umanah GK, Dephoure N, Andrabi SA, Gygi SP, Dawson TM, Dawson VL, Rutter J. EMBO J. 2014 May 19. pii: e201487943. [Epub ahead of print] PMID: 24843043
Parkin and PINK1: much more than mitophagy. Scarffe LA, Stevens DA, Dawson VL, Dawson TM. Trends Neurosci. 2014 Apr 13. pii: S0166-2236(14)00043-5. doi: 10.1016/j.tins.2014.03.004. [Epub ahead of print] Review. PMID: 24735649
Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, Stankowski J, Kim MS, Zhong J, Kumar M, Andrabi SA, Xiong Y, Dickson DW, Wszolek ZK, Pandey A, Dawson TM, Dawson VL. Cell. 2014 Apr 10;157(2):472-85. doi: 10.1016/j.cell.2014.01.064. PMID: 24725412
The c-Abl inhibitor, Nilotinib, protects dopaminergic neurons in a preclinical animal model of Parkinson's disease. Karuppagounder SS, Brahmachari S, Lee Y, Dawson VL, Dawson TM, Ko HS. Sci Rep. 2014 May 2;4:4874. doi: 10.1038/srep04874. PMID: 24786396

Honors

Dean's Lecture, Johns Hopkins University School of Medicine
Javits Neuroscience Investigator Award, 1/1/14
Fellow, American Heart Association (F.A.H.A.) and the Council on Basic Cardiovascular Sciences, 1/1/14
Thomson Reuters, The Worlds Most Influential Minds, 1/1/14
Thomson Reuters Highly Cited Researcher, 1/1/14
American Association for the Advancement of Science, Fellow, 1/1/13
Potter Lectureship, Thomas Jefferson University, 1/1/12
NINDS Stroke Progress Review Group, Genomics/Proteomics section, 1/1/11
SfN Program Committee, 1/1/11
Senior Editor, Journal of Neuroscience, 1/1/10
Professional Development Committee, SfN, 1/1/09
SfN Young Investigator Award Committee, Society for Neuroscience, 1/1/07
Committee on Women in Neuroscience, SfN, 1/1/07
NINDS K99-R00 Review Panel, Chair, 1/1/06
NINDS Stroke Progress Review Group, Genomics/Proteomics section, 1/1/06
ISI Highly Cited, 1/1/06
Faculty of 1000, 1/1/06
American Academy of Neurology, Frontiers in Clinical Neuroscience, 1/1/05
American Heart Steering Committee, 1/1/05
Co-Chair, American Heart Association National Review, 1/1/04
ISI Highly Cited, 1/1/04
McKnight Neuroscience of Brain Disorders, 1/1/04
Reviewing Editor, Journal of Neuroscience, 1/1/03
Leadership Development Program, Johns Hopkins University, 1/1/02
Establish Investigator Award, American Heart Association, 1/1/01
Section Reviewer, NINDS NSDA, 1/1/00
Mary Lou McIlhany Scholar, 1/1/99
International Society for Neurochemistry Young Investigator, 1/1/99
Staglin Music Festival Investigator, 1/1/98
NARSAD Independent Investigator Award, 1/1/98
Virginia Davids Scholar, 1/1/98
Amyotrophic Lateral Sclerosis Association, 1/1/97
Muscular Dystrophy Association, 1/1/97
Grant-In-Aid Award, American Heart Association, 1/1/96
National Institutes of Health, NINDS R29 NS33142-01A1, 1/1/95
Muscular Dystrophy Association, 1/1/95
Scholar Award, Alzheimer's Association, 1/1/94
Young Investigator Award, NARSAD, 1/1/94
Grant-In-Aid Award, American Heart Association, 1/1/94
Scholar Award, AmFAR, 1/1/94
Staff Fellow Award, National Institute on Drug Abuse, 1/1/92
Intramural Research Training Award, ADAMHA, 1/1/92
Winter Conference on Brain Research Fellowship, Vail, 1/1/91
PRAT Fellowship, National Institutes of Health, 1/1/90
Grant #GMO 7579-07, National Institutes of Health Training, 1/1/85
Student Orientation Leader Traineeship, University of California at Davis, 1/1/81
Bekins Scholarship Foundation, 1/1/79
Italian-American Club Scholarship Foundation, 1/1/79

Lectures & Presentations

"Parthanatos" 2012 Cell Death, Gordon Research Conference, Castel Vecchio Pascoli, Lucca, Italy, 1/1/12
AMPA Receptor Surface Expression is Regulated by S-Nitrosylation of Thorase, Gordon Research Conference - Nitric Oxide, Ventura, 1/1/15
Cell survival and death events following brain ischemia, Fellows Lecture Series, Johns Hopkins University School of Medicine - Department of Neurology, MD, 1/1/12
Changes to the Maryland Stem Cell Commission, WYPR Maryland Morning with Sheilah Kast, 3/9/09
Exploring the biochemical and molecular signaling of familial Parkinson's disease reveals new pathways to neurodegeneration, Science Symposium on Biological Complexity: Neurodegenerative Diseases, Salk Institute, San Diego, 1/1/15
Genetic Clues to the Mystery of Parkinson's Disease., 4th Annual Young-Onset Parkinson Network Conference, National Parkinson Foundation, Reston, VA, 1/1/06
Life and Death Decisions: Influence of Poly (ADP-Ribose) Signaling, Research and Education in Memory Impairments and Neurological Disorders (ReMIND), Annual Emerging Scientist Symposium, Institute for Memory Impairments and Neurological Disorders (iMIND), Irvine, 1/1/14
Life and Death Decisions: Influence of Poly (ADP-Ribose) Signaling., Research and Education in Memory Impairments and Neurological Disorders (ReMIND), Annual Emerging Scientist Symposium, Institute for Memory Impairments and Neurological Disorders (iMIND), University of California, Irvine, 1/1/14
Mechanisms of Cell Death in Neurodegeneration, New Frontiers in Neurodegenerative Disease Research, Keystone Symposium, New Mexico, 1/1/13
Mechanisms of Cell Death in Neurodegeneration, Keystone Symposium, New Frontiers in Neurodegenerative Disease Research, Santa Fe, New Mexico, 1/1/13
Neuronal cell death in acute brain injury: an overview, Keynote Lecture, Brain Repair: Bench to Bedside" Versaille, Versailles International Neurointensive Care Symposium 2012 "Brain Injury, France, 1/1/12
Neuronal cell death in acute brain injury: an overview., Keynote Lecture, Versailles International Neurointensive Care Symposium 2012 "Brain Injury", Brain Repair: Bench to Bedside", Versaille, France, 1/1/12
New Opportunities to Repair the Brain., Legacy Lunch, Department of Neurology, Johns Hopkins, Baltimore, MD, 1/1/07
Nitric Oxide and Schizophrenia. National Alliance for Research on Schizophrenia and Depression, New York, NY, 1/1/96
Nitric Oxide and Schizophrenia. National Alliance for the Mentally Ill, Washington, DC, 1/1/96
Novel Signaling Pathways in Models of Parkinson's Disease, 2013 Bevill Conference on Mechanisms of Neurodegeneration, University of Alabama, Birmingham, Alabama, 1/1/13
Novel Signaling Pathways in Models of Parkinson's Disease" 2013 Bevill Conference on Mechanisms of Neurodegeneration at theUniversity of Alabama at Birmingham, Alabama, 1/1/13
PAR Network Regulating Survival and Death in the Brain, The 2012 William Potter lecture, Thomas Jefferson University, Philadelphia PA, 1/1/12
PAR Network Regulating Survival and Death in the Brain., The 2012 William Potter lecture, Thomas Jefferson University, Philadelphia, PA, 1/1/12
PAR Regulation of Survival and Death in the Brain, Bioscience Seminar, University of South Florida - Department of Molecular Medicine, FL, 1/1/12
PARP activation and AIF release as mediators of parthanatos and neuronal injury, Autophagy and Protein Translation in Neurological Disorders, Neurons Under Stress - Bioenergetics, Royal College of Surgeons in Ireland, Ireland, 1/1/12
Parthanatos, 2012 Cell Death - Gordon Research Conference, Castel Vecchio Pascoli, Italy, 1/1/12
Parthanatos Signaling in Stroke and Parkinson's disease, Neuroscience Program, Washington University - Department of Anatomy and Neurobiology, St. Louis MO, 1/1/12
Parthanatos Signaling in Stroke and Parkinson's disease., Department of Anatomy and Neurobiology: Neuroscience Program, Washington University, St. Louis, MO, 1/1/12
Rebuilding the Brain., Palm Beach, FL, 1/1/05
Regulation of Life and Death Decisions by Novel Cell Signaling Molecules, Ajou University, South Korea, 1/1/12
Regulation of Life and Death Decisions by Novel Cell Signaling Molecules, Ajou University, Suwon, South Korea, 1/1/12
Stem Cells, A Woman's Journey, Johns Hopkins University
Stroke., The American Alliance for Health, Physical Education, Recreation and Dance (AAHPERD) and the American Heart Association National Convention, Baltimore, MD, 1/1/07
The parkin substrate AIMP2 mediates selective dopaminergic neurotoxicity by Parthanatos., 17th Takeda Science Symposium on Bioscience, Osaka, Japan, 1/1/12
The parkin substrate, AIMP2 mediates selective dopaminergic neurotoxicity by Parthanatos, " 17th Takeda Science Symposium on Bioscience, Japan, 1/1/12
Therapeutic Opportunities From the Study of Molecular Mechanisms of Parkinson's disease, Grand Rounds Department of Neurology, Johns Hopkins University School of Medicine, MD, 1/1/14
Therapeutic Opportunities From the Study of Molecular Mechanisms of Parkinson's disease., Grand Rounds Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 1/1/14
Unraveling Cell Death Pathways in Parkinson's disease, 5th Annual Tufts Neuroscience Symposium & William Shucart Lecture, Tufts University School of Medicine, MA, 1/1/13
Unraveling Cell Death Pathways in Parkinson's disease, ?Johns Hopkins University School of Medicine - Department of Molecular & Comparative Pathobiology, Baltimore MD, 1/1/14
Unraveling Cell Death Pathways in Parkinson's disease., 5th Annual Tufts Neuroscience Symposium & William Shucart Lecture, Tufts University School of Medicine, Boston, MA, 1/1/13
Unraveling Cell Death Pathways in Parkinson's disease., Department of Molecular & Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, 1/1/14

Graduate Program Affiliations

Memberships

American Association for the Advancement of Science
American Heart Association
American Neurologic Association
International Society for Cerebral Blood Flow and Metabolism (ISCBFM)
International Society for Stem Cell Research
Society for Neuroscience
The New York Academy of Sciences
Women in Neuroscience

Professional Activities

Departments of Neurology The Johns Hopkins University School of Medicine, Director, 1/1/02
Division of Forensic Toxicology, Forensic Toxicology Trainee, 1/1/84
Institute for Cell Engineering The Johns Hopkins University School of Medicine, Director, 1/1/02
Institute for Cell Engineering The Johns Hopkins University School of Medicine, Director, 1/1/08
Institute for Cell Engineering The Johns Hopkins University School of Medicine, Director, 1/1/09 - 1/1/13
The Johns Hopkins University School of Medicine, Vice-Chair, 1/1/01 - 1/1/08