Valina L. Dawson, Ph.D.

Headshot of Valina L. Dawson
  • Director, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,
  • Professor of Neurology

Research Interests

Neuronal cell death; Parkinson's disease; Neuronal stem cell development; Neuronal cell survival ...read more

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.

...read more

Titles

  • Director, Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering,
  • Professor of Neurology
  • Professor of Neuroscience
  • Professor of Physiology

Departments / Divisions

Centers & Institutes

Education

Degrees

  • B.S.; University of California - Davis School of Medicine (California) (1983)
  • Ph.D.; University of Utah School of Medicine - Salt Lake Cty (Utah) (1989)

Research & Publications

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.

Technology Expertise Keywords

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

Selected Publications

View all on PubMed

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

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

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

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

Contact for Research Inquiries

Email me Phone: 410-614-3361

Academic Affiliations & Courses

Graduate Program Affiliation

Activities & Honors

Honors

  • Javits Neuroscience Investigator Award, 2014
  • Fellow, American Heart Association (F.A.H.A.) and the Council on Basic Cardiovascular Sciences, 2014
  • Co-Chair, American Heart Association National Review, 2004
  • NINDS K99-R00 Review Panel, Chair, 2006
  • American Association for the Advancement of Science, Fellow, 2013
  • American Academy of Neurology, Frontiers in Clinical Neuroscience, 2005
  • NINDS Stroke Progress Review Group, Genomics/Proteomics section, 2011
  • NINDS Stroke Progress Review Group, Genomics/Proteomics section, 2006
  • Dean’s Lecture, Johns Hopkins University School of Medicine
  • Senior Editor, Journal of Neuroscience, 2010
  • Reviewing Editor, Journal of Neuroscience, 2003
  • Staff Fellow Award, National Institute on Drug Abuse, 1992
  • PRAT Fellowship, National Institutes of Health, 1990 - 1992
  • National Institutes of Health, NINDS R29 NS33142-01A1, 1995 - 2000
  • SfN Young Investigator Award Committee, Society for Neuroscience, 2007 - 2009
  • Thomson Reuters, The Worlds Most Influential Minds, 2014
  • Potter Lectureship, Thomas Jefferson University, 2012
  • Winter Conference on Brain Research Fellowship, Vail, 1991
  • Professional Development Committee, SfN, 2009 - 2011
  • Committee on Women in Neuroscience, SfN, 2007 - 2010
  • Thomson Reuters Highly Cited Researcher, 2014
  • SfN Program Committee, 2011
  • ISI Highly Cited, 2006
  • Faculty of 1000, 2006
  • American Heart Steering Committee, 2005
  • ISI Highly Cited, 2004
  • McKnight Neuroscience of Brain Disorders, 2004
  • Leadership Development Program, Johns Hopkins University, 2002
  • Section Reviewer, NINDS NSDA , 2000 - 2004
  • Establish Investigator Award, American Heart Association , 2001
  • Mary Lou McIlhany Scholar, 1999 - 2007
  • International Society for Neurochemistry Young Investigator, 1999
  • Staglin Music Festival Investigator, 1998
  • NARSAD Independent Investigator Award, 1998 - 2001
  • Virginia Davids Scholar, 1998
  • Amyotrophic Lateral Sclerosis Association, 1997 - 1999
  • Muscular Dystrophy Association, 1997 - 1999
  • Grant-In-Aid Award, American Heart Association, 1996 - 1999
  • Muscular Dystrophy Association, 1995 - 1997
  • Scholar Award, Alzheimer's Association , 1994 - 1997
  • Young Investigator Award, NARSAD , 1994 - 1996
  • Grant-In-Aid Award, American Heart Association , 1994 - 1996
  • Scholar Award, AmFAR , 1994 - 1997
  • Intramural Research Training Award, ADAMHA, 1992 - 1993
  • Grant #GMO 7579-07, National Institutes of Health Training, 1985 - 1987
  • Bekins Scholarship Foundation, 1979 - 1983
  • Student Orientation Leader Traineeship, University of California at Davis, 1981
  • Italian-American Club Scholarship Foundation, 1979
  • , Beta Sigma Pi Scholarship Foundation, 1979

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

  • Director, Institute for Cell Engineering The Johns Hopkins University School of Medicine, 2002
  • Director, Institute for Cell Engineering The Johns Hopkins University School of Medicine, 2008
  • Director, Institute for Cell Engineering The Johns Hopkins University School of Medicine, 2009 - 2013
  • Director, Departments of Neurology The Johns Hopkins University School of Medicine, 2002
  • Forensic Toxicology Trainee, Division of Forensic Toxicology, 1984
  • Vice-Chair, The Johns Hopkins University School of Medicine, 2001 - 2008

Videos & Media

Lectures and Presentations

  • PAR Network Regulating Survival and Death in the Brain
    The 2012 William Potter lecture, Philadelphia PA (01/01/2012)
    Thomas Jefferson University
  • Parthanatos Signaling in Stroke and Parkinson’s disease
    Neuroscience Program, St. Louis MO (01/01/2012)
    Washington University - Department of Anatomy and Neurobiology
  • Neuronal cell death in acute brain injury: an overview
    Keynote Lecture, Brain Repair: Bench to Bedside” Versaille, France (01/01/2012)
    Versailles International Neurointensive Care Symposium 2012 “Brain Injury
  • Parthanatos
    2012 Cell Death - Gordon Research Conference, Italy (01/01/2012)
    Castel Vecchio Pascoli
  • Cell survival and death events following brain ischemia
    Fellows Lecture Series, MD (01/01/2012)
    Johns Hopkins University School of Medicine - Department of Neurology
  • PARP activation and AIF release as mediators of parthanatos and neuronal injury
    Autophagy and Protein Translation in Neurological Disorders, Neurons Under Stress - Bioenergetics, Ireland (01/01/2012)
     Royal College of Surgeons in Ireland
  • PAR Regulation of Survival and Death in the Brain
    Bioscience Seminar, FL (01/01/2012)
    University of South Florida - Department of Molecular Medicine
  • The parkin substrate, AIMP2 mediates selective dopaminergic neurotoxicity by Parthanatos
    Japan (01/01/2012)
    ” 17th Takeda Science Symposium on Bioscience
  • Regulation of Life and Death Decisions by Novel Cell Signaling Molecules
    South Korea (01/01/2012)
    Ajou University
  • Mechanisms of Cell Death in Neurodegeneration
    New Frontiers in Neurodegenerative Disease Research, New Mexico (01/01/2013)
    Keystone Symposium
  • Novel Signaling Pathways in Models of Parkinson’s Disease” 2013 Bevill Conference on Mechanisms of Neurodegeneration at theUniversity of Alabama at Birmingham
    Alabama (01/01/2013)
  • Unraveling Cell Death Pathways in Parkinson’s disease
    5th Annual Tufts Neuroscience Symposium & William Shucart Lecture, MA (01/01/2013)
    Tufts University School of Medicine
  • Life and Death Decisions: Influence of Poly (ADP-Ribose) Signaling
    Research and Education in Memory Impairments and Neurological Disorders (ReMIND), Annual Emerging Scientist Symposium, Irvine (01/01/2014)
    Institute for Memory Impairments and Neurological Disorders (iMIND)
  • Therapeutic Opportunities From the Study of Molecular Mechanisms of Parkinson’s disease
    Grand Rounds Department of Neurology, MD (01/01/2014)
    Johns Hopkins University School of Medicine
  • Unraveling Cell Death Pathways in Parkinson’s disease
    Baltimore MD (01/01/2014)
    ?Johns Hopkins University School of Medicine - Department of Molecular & Comparative Pathobiology
  • PAR Network Regulating Survival and Death in the Brain.
    The 2012 William Potter lecture, Philadelphia, PA (01/01/2012)
    Thomas Jefferson University
  • Parthanatos Signaling in Stroke and Parkinson’s disease.
    Department of Anatomy and Neurobiology: Neuroscience Program, St. Louis, MO (01/01/2012)
    Washington University
  • Neuronal cell death in acute brain injury: an overview.
    Keynote Lecture, Versailles International Neurointensive Care Symposium 2012 “Brain Injury", Versaille, France (01/01/2012)
    Brain Repair: Bench to Bedside”
  • “Parthanatos” 2012 Cell Death
    Gordon Research Conference, Lucca, Italy (01/01/2012)
    Castel Vecchio Pascoli
  • The parkin substrate AIMP2 mediates selective dopaminergic neurotoxicity by Parthanatos.
    17th Takeda Science Symposium on Bioscience, Osaka, Japan (01/01/2012)
  • Regulation of Life and Death Decisions by Novel Cell Signaling Molecules
    Suwon, South Korea (01/01/2012)
    Ajou University
  • Mechanisms of Cell Death in Neurodegeneration
    Keystone Symposium, New Frontiers in Neurodegenerative Disease Research, Santa Fe, New Mexico (01/01/2013)
  • Novel Signaling Pathways in Models of Parkinson’s Disease
    2013 Bevill Conference on Mechanisms of Neurodegeneration, University of Alabama, Birmingham, Alabama (01/01/2013)
  • Unraveling Cell Death Pathways in Parkinson’s disease.
    5th Annual Tufts Neuroscience Symposium & William Shucart Lecture, Boston, MA (01/01/2013)
    Tufts University School of Medicine
  • Life and Death Decisions: Influence of Poly (ADP-Ribose) Signaling.
    Research and Education in Memory Impairments and Neurological Disorders (ReMIND), Annual Emerging Scientist Symposium, University of California, Irvine (01/01/2014)
    Institute for Memory Impairments and Neurological Disorders (iMIND)
  • Therapeutic Opportunities From the Study of Molecular Mechanisms of Parkinson’s disease.
    Grand Rounds Department of Neurology, Baltimore, MD (01/01/2014)
    Johns Hopkins University School of Medicine
  • Unraveling Cell Death Pathways in Parkinson’s disease.
    Department of Molecular & Comparative Pathobiology, Baltimore, MD (01/01/2014)
    Johns Hopkins University School of Medicine
  • Nitric Oxide and Schizophrenia. National Alliance for Research on Schizophrenia and Depression
    New York, NY (01/01/1996)
  • Nitric Oxide and Schizophrenia. National Alliance for the Mentally Ill
    Washington, DC (01/01/1996)
  • Rebuilding the Brain.
    Palm Beach, FL (01/01/2005)
  • Genetic Clues to the Mystery of Parkinson's Disease.
    4th Annual Young-Onset Parkinson Network Conference, Reston, VA (01/01/2006)
    National Parkinson Foundation
  • Stroke.
    The American Alliance for Health, Physical Education, Recreation and Dance (AAHPERD) and the American Heart Association National Convention, Baltimore, MD (01/01/2007)
  • New Opportunities to Repair the Brain.
    Legacy Lunch, Baltimore, MD (01/01/2007)
    Department of Neurology, Johns Hopkins
  • Changes to the Maryland Stem Cell Commission
    WYPR Maryland Morning with Sheilah Kast (03/09/2009)
  • Stem Cells, A Woman’s Journey, Johns Hopkins University
  • Exploring the biochemical and molecular signaling of familial Parkinson’s disease reveals new pathways to neurodegeneration
    Science Symposium on Biological Complexity: Neurodegenerative Diseases, San Diego (01/01/2015)
    Salk Institute
  • AMPA Receptor Surface Expression is Regulated by S-Nitrosylation of Thorase
    Gordon Research Conference – Nitric Oxide, Ventura (01/01/2015)
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