Welcome to the Dawson Lab

BACKGROUND

Dr. Dawson has dedicated his career to deciphering the mechanisms that control neurodegeneration and neuronal cell death. Dawson attended Montana State University and received a B.S. in Premedicine in 1981 with highest honors.  He received a M.D. and Ph.D. in Pharmacology in 1986 from the University of Utah where he also completed an Internship in Internal Medicine.  At the Hospital of the University of Pennsylvania, he completed a Neurology Residency in 1990.  After postdoctoral training with Solomon H. Snyder and a clinical movement disorder fellowship at Johns Hopkins University School of Medicine, he joined the Departments of Neurology and Neuroscience in 1994 and became Professor in 2000. From 1996 to 2010 he was director of the Parkinson’s Disease and Movement Disorder Center. He co-founded the Neuroregeneration Program in the Institute for Cell Engineering in 2002 and became the Scientific Director of the Institute for Cell Engineering in 2010 and its Executive Director in 2011.  He is currently the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and Director of the Institute for Cell Engineering.

Dawson’s honors include the Derek Denny-Brown Young Neurological Scholar Award from the American Neurological Association, the Paul Beeson Physician Faculty Scholar Award, the Santiago Grisolia Medal Santiago Grisolia Medal, Thomson Reuters Highly Cited Researcher Award(s) and Worlds’ Most Influential Scientific Minds and the Javits Neuroscience Investigator Award. He was elected to the Association of American Physicians and is a Fellow of the American Association for the Advancement of Science, American Academy of Neurology, the American Heart Association, and the National Academy of Inventors. He is a member of the National Academy of Medicine. He has served and serves on foundations, editorial boards, and professional societies. 

Dr. Dawson studies of nitric oxide (NO) led to major insights into the neurotransmitter functions of this gaseous messenger molecule. He pioneered the role of NO in neuronal injury in Parkinson’s disease, stroke, and excitotoxicity. He showed that NO derived from neuronal NO synthase and immunologic NO synthase leads to degeneration of dopamine neurons through cell autonomous and non-cell autonomous affects, respectively. Dawson elucidated the molecular mechanisms by which NO kills neurons through the actions of poly (ADP-ribose) (PAR) polymerase (PARP) and discovered a unique cell death pathway designated parthanatos, in which PAR functions as an intracellular signaling molecule that induces the release of apoptosis inducing factor (AIF) causing cell death via the recruitment of the nuclease, macrophage migration inhibitory factor (MIF). Dawson identified the first in class MIF nuclease inhibitor that is protective in models of PD. He showed that poly (ADP-ribose) glycohydrolase, which degrades PAR polymer is an endogenous inhibitor of parthanatos.  In screens for neuroprotective proteins, he discovered another endogenous inhibitor of parthanatos, Iduna (RNF146), a first in class PAR-dependent E3 ligase. In the same screens, he also discovered Thorase, an AAA+ ATPase that regulates glutamate (AMPA) receptor trafficking, mTor signaling, and discovered that Thorase is an important regulator of synaptic plasticity, learning and memory.  Botch was also discovered as in important inhibitor of Notch signaling via deglycination of Notch preventing Notch’s intracellular processing at the level of the Golgi, playing an important role in neuronal development. 

Dawson has also been at the forefront of research into the biology and pathobiology of the proteins and mutant proteins linked to Parkinson’s disease. Dr. Dawson showed that parkin is a ubiquitin E3 ligase that is inactivated in patients with genetic mutations in parkin and that it is also inactivated in sporadic Parkinson’s disease via S-nitrosylation and c-Abl tyrosine phosphorylation leading to accumulation of pathogenic substrates. He showed that c-Abl is overactive in PD and that interfering with c-Abl activity prevents neurodegeneration in PD models leading to clinical trials of c-Abl inhibitors.  He discovered the parkin substrate, PARIS, which plays a key pathogenic role in PD pathogenesis by inhibiting mitochondrial biogenesis. He also showed that the parkin substrate, AIMP2 is a non-conical activator of PARP, that contributes to neurodegeneration in PD.  He showed that DJ-1 is an atypical peroxidoxin-like peroxidase and that its absence in PD leads to mitochondrial dysfunction. He showed that mutations in LRRK2 cause PD through pathologic kinase activity leading to enhanced protein translation via the phosphorylation of the ribosomal protein s15 and that inhibiting LRRK2 is protective. His laboratory discovered that pathologic a-synuclein spreads in the nervous system via engagement with the lymphocyte-activation gene 3 (LAG3).  In collaborative studies, Dawson showed that neurotoxic reactive astrocytes contribute to neurodegeneration in PD and other neurodegenerative disease and identified a brain penetrant GLP1 receptor agonist that is neuroprotective by preventing microglial and neurotoxic reactive astrocyte activation that is currently in clinical trials.  The laboratory is building on these studies and investigating the role of innate and adaptive immunity in PD and recently showed that STING activation contributes to neurodegeneration in PD.  It also showed NLRP3 is a parkin substrate leading to activation of the NLRP3 inflammasome in a PARIS dependent manner contributing to neurodegeneration in PD.

Collectively, these studies are providing major insights into understanding the pathogenesis of PD, stroke, and related neurologic disorders, providing novel opportunities for therapies aimed at preventing the degenerative process of PD and other neurologic disorders.