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Ted M. Dawson (born April 19, 1959) is an American neurologist and neuroscientist. He is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases [1] and Director of the Institute for Cell Engineering [2] at Johns Hopkins University School of Medicine. He has joint appointments in the Department of Neurology, [3] Neuroscience [4] and Department of Pharmacology and Molecular Sciences. [5]
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He graduated with a bachelor's degree from Montana State University in 1981. He earned his M.D. and Ph.D. degrees from the University of Utah School of Medicine in 1986. He furthered his medical training with an Internship in Internal Medicine at the University of Utah Affiliated Hospitals and a Neurology Residency at the Hospital of the University of Pennsylvania. In 1992, Dawson completed a Postdoctoral Fellowship in Neurosciences under Solomon H. Snyder at the Johns Hopkins University School of Medicine.
Dawson began work at The Johns Hopkins University School of Medicine where he was made Assistant Professor in the Department of Neuroscience in 1993 and in the Departments of Neurology and Neuroscience in 1994. In 1996, he became an Associate Professor in the Departments of Neurology and Neuroscience and Graduate Program in Cellular and Molecular Medicine, as well as the Co-Director of the Parkinson's Disease and Movement Disorder Center. In 1998, Dawson became the Director of the Morris K. Udall Parkinson's Disease Research Center of Excellence, [6] a position he currently holds. Still at The Johns Hopkins University School of Medicine, Dawson achieved a Professor position in the Departments of Neurology and Neuroscience in 2000. Dawson was a founder and Director of the Neuroregeneration and Repair Program at the Institute for Cell Engineering in 2002 and is now the Director of the Institute. In 2004 he was named the inaugural Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases in the departments of Neurology and Neuroscience at The Johns Hopkins School of Medicine.[ citation needed ]
He served as the chairman of the Scientific Advisory Board of the Bachman-Strauss Dystonia and Parkinson Foundation. [7] He serves on Scientific Advisory Board (SAB) of the CurePSP. [8] He serves on the Advisory Council of Aligning Science Across Parkinson's [9] and the Executive Scientific Advisory Board of the Michael J. Fox Foundation. He is also a member of numerous editorial boards including the Journal of Clinical Investigation and Cell. He was a founder of AGY Therapeutics. [10] He is a founder and is on the Scientific Advisory Board of Neuraly [11] and Valted Seq, Inc.
In 2022 he was named to the National Academy of Inventors. [12] [13]
Dawson works closely with his wife and partner, Valina L. Dawson. The research performed in their laboratories studies the molecular mechanisms that lead to neuronal cell death in neurodegenerative diseases, stroke and trauma. They discovered the role of nitric oxide (NO) in neuronal injury in stroke and excitotoxicity [14] [15] [16] along with their mentor Solomon H. Snyder. [17] The Dawsons showed that NO derived from neuronal NO synthase and immunologic NO synthase leads to degeneration of dopamine neurons in models of Parkinson's disease through cell autonomous and non-cell autonomous affects, respectively. [18] [19] They identified the mechanisms by which NO kills neurons through poly (ADP-ribose) polymerase. [20] [21] [22] They discovered that poly (ADP-ribose) (PAR) polymer, the byproduct of PARP activation, is a novel cell death signaling molecule that plays a critical role in neuronal injury [23] [24] through apoptosis inducing factor [25] [26] [27] and activation of nuclease activity of macrophage migration inhibitory factor [28] in a cell death pathway designated parthanatos. They showed that poly (ADP-ribose) glycohydrolase, which degrades PAR polymer is an endogenous inhibitor of parthanatos. [29] In screens for neuroprotective proteins, they discovered an endogenous inhibitor of parthanatos, Iduna (RNF146), a first in class PAR-dependent E3 ligase. [30] [31] In the same screens, they also discovered Thorase, an AAA+ ATPase that regulates glutamate (AMPA) receptor trafficking and discovered that Thorase is an important regulator of synaptic plasticity, learning and memory. [32] Variants in Thorase were found to be linked to schizophrenia and expression of these variants in mice lead to behavioral deficits that are rescued by the AMPA receptor antagonist Perampenal. [33] They also showed that mutations in Thorase leading to gain or loss of function result in lethal developmental disorders in children. [34] [35] Botch was also discovered as an important inhibitor of Notch signaling via deglycation of Notch preventing Notch's intracellular processing at the level of the Golgi, playing an important role in neuronal development. [36] [37]
The Dawsons have also been at the forefront of research into the biology and pathobiology of the proteins and mutant proteins linked to Parkinson's disease. They showed that parkin is a ubiquitin E3 ligase that is inactivated in patients with genetic mutations in parkin [38] and that it is also inactivated in sporadic Parkinson's disease via S-nitrosylation [39] and c-Abl tyrosine phosphorylation [40] leading to accumulation of pathogenic substrates. They have also shown the c-Abl plays a prominent role in the pathogenesis of Parkinson's disease due to pathologic α-synuclein. [41] They discovered the parkin substrate, PARIS, which plays a key pathogenic role in PD pathogenesis by inhibiting mitochondrial biogenesis. [42] [43] [44] They showed that DJ-1 is an atypical peroxidoxin-like peroxidase and that its absence in PD leads to mitochondrial dysfunction. [45] The Dawsons showed that mutations in LRRK2 cause PD through pathologic kinase activity [46] [47] leading to enhanced protein translation via the phosphorylation of the ribosomal protein s15 [48] and that inhibiting LRRK2 kinase activity is protective. [49] In collaborative studies, they identified Rab35 as the key Rab linked to LRRK2 neurotoxicity. [50] Their labs also discovered that pathologic α-synuclein spreads in the nervous system via engagement with the lymphocyte-activation gene 3 (LAG3). [51] In further collaborative studies, they discovered that Glucagon-like peptide-1 receptor (GLP1R) agonist, NLY01, prevents neuroinflammaory damage induced by pathologic α-synuclein in Parkinson's disease via inhibition of microglia and prevention of the conversion of resting astrocytes to activated A1 astrocytes. [52] These studies are providing major insights into understanding the pathogenesis of PD and are providing novel opportunities for therapies aimed at preventing the degenerative process of PD and other neurologic disorders.
Dawson has published over 550 publications and has an H-index of 150. [53]
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Dawson Lab; Institute for Cell Engineering Johns Hopkins University School of Medicine [56]
Ampakines or AMPAkines are a subgroup of AMPA receptor positive allosteric modulators with a benzamide or closely related chemical structure. They are also known as "CX compounds". Ampakines take their name from the AMPA receptor (AMPAR), a type of ionotropic glutamate receptor with which the ampakines interact and act as positive allosteric modulators (PAMs) of. Although all ampakines are AMPAR PAMs, not all AMPAR PAMs are ampakines.
Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death.
Angiogenin (ANG) also known as ribonuclease 5 is a small 123 amino acid protein that in humans is encoded by the ANG gene. Angiogenin is a potent stimulator of new blood vessels through the process of angiogenesis. Ang hydrolyzes cellular RNA, resulting in modulated levels of protein synthesis and interacts with DNA causing a promoter-like increase in the expression of rRNA. Ang is associated with cancer and neurological disease through angiogenesis and through activating gene expression that suppresses apoptosis.
Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin and PARK8, is a large, multifunctional kinase enzyme that in humans is encoded by the LRRK2 gene. LRRK2 is a member of the leucine-rich repeat kinase family. Variants of this gene are associated with an increased risk of Parkinson's disease and Crohn's disease.
This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most highly similar to GRK4 and GRK5. The protein phosphorylates the activated forms of G protein-coupled receptors to regulate their signaling.
MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene.
Interleukin-18-binding protein is a protein that in humans is encoded by the IL18BP gene.
Poly [ADP-ribose] polymerase 4 is an enzyme that in humans is encoded by the PARP4 gene.
60 kDa SS-A/Ro ribonucleoprotein is a protein that in humans is encoded by the TROVE2 gene.
Nucleus accumbens-associated protein 1 is a protein that in humans is encoded by the NACC1 gene.
Poly(A) polymerase alpha is an enzyme that in humans is encoded by the PAPOLA gene.
Poly [ADP-ribose] polymerase 3 is an enzyme that in humans is encoded by the PARP3 gene.
Calcium-activated potassium channel subunit beta-2 is a protein that in humans is encoded by the KCNMB2 gene.
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B is an enzyme that in humans is encoded by the PDE1B gene.
TCDD-inducible poly [ADP-ribose] polymerase is an enzyme that in humans is encoded by the TIPARP gene.
IQ motif and SEC7 domain-containing protein 1 also known as ARF-GEP100 (ADP-Ribosylation Factor - Guanine nucleotide-Exchange Protein - 100-kDa) is a protein that in humans is encoded by the IQSEC1 gene.
Poly [ADP-ribose] polymerase 10 is an enzyme that in humans is encoded by the PARP10 gene.
Epoxomicin is a naturally occurring selective proteasome inhibitor with anti-inflammatory activity. It was originally discovered in 1992. Injected, it can induce Parkinson's-like symptoms in rats.
Parthanatos is a form of programmed cell death that is distinct from other cell death processes such as necrosis and apoptosis. While necrosis is caused by acute cell injury resulting in traumatic cell death and apoptosis is a highly controlled process signalled by apoptotic intracellular signals, parthanatos is caused by the accumulation of Poly(ADP ribose) (PAR) and the nuclear translocation of apoptosis-inducing factor (AIF) from mitochondria. Parthanatos is also known as PARP-1 dependent cell death. PARP-1 mediates parthanatos when it is over-activated in response to extreme genomic stress and synthesizes PAR which causes nuclear translocation of AIF. Parthanatos is involved in diseases that afflict hundreds of millions of people worldwide. Well known diseases involving parthanatos include Parkinson's disease, stroke, heart attack, and diabetes. It also has potential use as a treatment for ameliorating disease and various medical conditions such as diabetes and obesity.
Valina L. Dawson is an American neuroscientist who is the director of the Programs in Neuroregeneration and Stem Cells at the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. She has joint appointments in the Department of Neurology, Neuroscience and Physiology. She is a member of the Graduate Program in Cellular and Molecular Medicine and Biochemistry, Cellular and Molecular Biology.