Ted M. Dawson

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]

Early life and education

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.

Career

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]}

Research

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]

Awards

• Ruth Salta Junior Investigator Achievement Award, for Outstanding Contribution in Alzheimer's Disease Research
• The Paul Beeson Physician Faculty Scholars in Aging Research Program
• Elected to the American Neurological Association
• Derek Denny-Brown Young Neurological Scholar Award, American Neurological Association
• International Life Sciences Institute Award
• Santiago Grisoliá Chair and Medal
• Elected to the Association of American Physicians
• Elected Fellow, American Association for the Advancement of Science
• Thomson Reuters Highly Cited Researcher
• Thomson Reuters Worlds’ Most Influential Scientific Minds
• Javits Neuroscience Investigator Award
• Elected Fellow of the National Academy of Inventors ^[54]
• Elected Fellow of the American Neurological Association
• Elected Fellow of the American Academy of Neurology
• Elected Fellow of the American Heart Association
• Distinguished Professorship, Xiangya Hospital, Central South University, Changsha, China ^[55]

External links

Dawson Lab; Institute for Cell Engineering Johns Hopkins University School of Medicine ^[56]

References

1. "Leonard and Madlyn Abramson Professorship in Neurodegenerative Diseases - Named Deanships, Directorships, and Professorships".
2. "The Johns Hopkins Institute for Cell Engineering (ICE) in Baltimore, Maryland".
3. "Neurology and Neurosurgery".
4. "The Solomon H Snyder Department of Neuroscience". neuroscience.jhu.edu.
5. "Pharmacology and Molecular Sciences".
6. "Parkinson's Disease Centers of Excellence - National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov.
7. "Bachmann Strauss Dystonia & Parkinson Foundation, Inc. -". www.dystonia-parkinsons.org.
8. "CurePSP, the Leading Organization for Prime of Life Neurodegeneration". CurePSP.
9. "ASAP: Aligning Science Across Parkinson's". ASAP.
10. "AGY Therapeutics Inc". www.agyinc.com.
11. Andy. "Biohealth Innovation - Neuraly Inc". www.biohealthinnovation.org.
12. "National Academy of Inventors names new fellows". www.asbmb.org. Retrieved 2022-10-19.
13. "Three from Hopkins named to National Academy of Inventors". The Hub. 2021-12-20. Retrieved 2022-10-19.
14. Dawson,T.M.; et al. (1993). "Nitric oxide as a mediator of neurotoxicity". NIDA Res Monogr. 136: 258–71, discussion 271–3. PMID   7507221.
15. Dawson, T. M.; et al. (1992). "A novel neuronal messenger molecule in brain: the free radical, nitric oxide". Ann Neurol. 32 (3): 297–311. doi:10.1002/ana.410320302. PMID   1384420. S2CID   8772497.
16. Dawson, V. L.; et al. (1996). "Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice". J Neurosci. 16 (8): 2479–87. doi:10.1523/JNEUROSCI.16-08-02479.1996. PMC   6578778 . PMID   8786424.
17. Dawson, T. M.; et al. (2018). "Nitric Oxide Signaling in Neurodegeneration and Cell Death". Apprentices to Genius: A tribute to Solomon H. Snyder. Advances in Pharmacology. Vol. 82. pp. 57–83. doi:10.1016/bs.apha.2017.09.003. ISBN   9780128140871. PMID   29413528.
18. Liberatore, G.T.; et al. (1999). "Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease". Nat Med. 5 (12): 1403–9. doi:10.1038/70978. PMID   10581083. S2CID   38247532.
19. Przedborski, S.; et al. (1996). "Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity". Proc Natl Acad Sci U S A. 93 (10): 4565–71. Bibcode:1996PNAS...93.4565P. doi: 10.1073/pnas.93.10.4565 . PMC   39317 . PMID   8643444.
20. Eliasson, M.J.; et al. (1997). "Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia". Nat Med. 3 (10): 1089–95. doi:10.1038/nm1097-1089. PMID   9334719. S2CID   32410245.
21. Mandir, A.S.; et al. (1999). "Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism". Proc Natl Acad Sci U S A. 96 (10): 5774–9. Bibcode:1999PNAS...96.5774M. doi: 10.1073/pnas.96.10.5774 . PMC   21936 . PMID   10318960.
22. Zhang, J.; et al. (1994). "Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity". Science. 263 (5147): 687–9. Bibcode:1994Sci...263..687Z. doi:10.1126/science.8080500. PMID   8080500.
23. Andrabi, S.A.; et al. (2006). "Poly(ADP-ribose) (PAR) polymer is a death signal". Proc Natl Acad Sci U S A. 103 (48): 18308–13. Bibcode:2006PNAS..10318308A. doi: 10.1073/pnas.0606526103 . PMC   1838747 . PMID   17116882.
24. Yu, S.W.; et al. (2006). "Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death". Proc Natl Acad Sci U S A. 103 (48): 18314–9. Bibcode:2006PNAS..10318314Y. doi: 10.1073/pnas.0606528103 . PMC   1838748 . PMID   17116881.
25. Wang, H.; et al. (2006). "Apoptosis-inducing factor substitutes for caspase executioners in NMDA-triggered excitotoxic neuronal death". J Neurosci. 24 (48): 10963–73. doi:10.1523/JNEUROSCI.3461-04.2004. PMC   6730219 . PMID   15574746.
26. Wang, Y.; et al. (2011). "Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos)". Sci Signal. 4 (167): ra20. doi:10.1126/scisignal.2000902. PMC   3086524 . PMID   21467298.
27. Yu, S.W.; et al. (2002). "Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor". Science. 297 (5579): 259–63. Bibcode:2002Sci...297..259Y. doi:10.1126/science.1072221. PMID   12114629. S2CID   22991897.
28. Wang, Y.; et al. (2016). "A nuclease that mediates cell death induced by DNA damage and poly(ADP-ribose) polymerase-1". Science. 354 (6308): aad6872. doi:10.1126/science.aad6872. PMC   5134926 . PMID   27846469.
29. Koh, D.W.; et al. (2004). "Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality". Proc Natl Acad Sci U S A. 101 (51): 17699–704. Bibcode:2004PNAS..10117699K. doi: 10.1073/pnas.0406182101 . PMC   539714 . PMID   15591342.
30. Andrabi, S.A.; et al. (2011). "Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death". Nat Med. 17 (6): 692–9. doi:10.1038/nm.2387. PMC   3709257 . PMID   21602803.
31. Kang, H.C.; et al. (2011). "Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage". Proc Natl Acad Sci U S A. 108 (34): 14103–8. Bibcode:2011PNAS..10814103K. doi: 10.1073/pnas.1108799108 . PMC   3161609 . PMID   21825151.
32. Zhang, J.; et al. (2011). "The AAA+ ATPase Thorase regulates AMPA receptor-dependent synaptic plasticity and behavior". Cell. 145 (2): 284–99. doi:10.1016/j.cell.2011.03.016. PMC   3085003 . PMID   21496646.
33. Umanah, G.K.E.; et al. (2017). "Thorase variants are associated with defects in glutamatergic neurotransmission that can be rescued by Perampanel". Sci Transl Med. 9 (420): 284–99. doi:10.1126/scitranslmed.aah4985. PMC   6573025 . PMID   29237760.
34. Ahrens-Nicklas, R.C.; et al. (2017). "Precision therapy for a new disorder of AMPA receptor recycling due to mutations in ATAD1". Neurology: Genetics. 3 (1): e130. doi:10.1212/NXG.0000000000000130. PMC   5289017 . PMID   28180185.
35. Piard, J.; et al. (2018). "A homozygous ATAD1 mutation impairs postsynaptic AMPA receptor trafficking and causes a lethal encephalopathy". Brain. 141 (3): 651–661. doi:10.1093/brain/awx377. PMC   5837721 . PMID   29390050.
36. Chi, Z.; et al. (2014). "Botch is a gamma-glutamyl cyclotransferase that deglycinates and antagonizes Notch". Cell Rep. 7 (3): 681–8. doi:10.1016/j.celrep.2014.03.048. PMC   4031649 . PMID   24767995.
37. Chi, Z.; et al. (2012). "Botch promotes neurogenesis by antagonizing Notc". Dev Cell. 22 (4): 707–20. doi:10.1016/j.devcel.2012.02.011. PMC   3331935 . PMID   22445366.
38. Zhang, Y.; et al. (2000). "Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1". Proc Natl Acad Sci U S A. 97 (24): 13354–9. Bibcode:2000PNAS...9713354Z. doi: 10.1073/pnas.240347797 . PMC   27228 . PMID   11078524.
39. Chung, K. K.; et al. (2004). "S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function". Science. 304 (5675): 1328–31. Bibcode:2004Sci...304.1328C. doi:10.1126/science.1093891. PMID   15105460. S2CID   86854030.
40. Ko, H.S.; et al. (2010). "Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function". Proc Natl Acad Sci U S A. 107 (38): 16691–6. Bibcode:2010PNAS..10716691K. doi: 10.1073/pnas.1006083107 . PMC   2944759 . PMID   20823226.
41. Brahmachari, S.; et al. (2016). "Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration". J Clin Invest. 126 (8): 2970–88. doi:10.1172/JCI85456. PMC   4966315 . PMID   27348587.
42. Lee, Y.; et al. (2017). "PINK1 Primes Parkin-Mediated Ubiquitination of PARIS in Dopaminergic Neuronal Survival". Cell Rep. 18 (4): 918–932. doi:10.1016/j.celrep.2016.12.090. PMC   5312976 . PMID   28122242.
43. Shin, J. H.; et al. (2011). "PARIS (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson's disease". Cell. 144 (5): 689–702. doi:10.1016/j.cell.2011.02.010. PMC   3063894 . PMID   21376232.
44. Stevens, D. A.; et al. (2015). "Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration". Proc Natl Acad Sci U S A. 112 (37): 11696–701. Bibcode:2015PNAS..11211696S. doi: 10.1073/pnas.1500624112 . PMC   4577198 . PMID   26324925.
45. Andres-Mateos, E.; et al. (2007). "DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase". Proc Natl Acad Sci U S A. 104 (37): 14807–12. Bibcode:2007PNAS..10414807A. doi: 10.1073/pnas.0703219104 . PMC   1976193 . PMID   17766438.
46. Smith, W. W.; et al. (2006). "Kinase activity of mutant LRRK2 mediates neuronal toxicity". Nat Neurosci. 9 (10): 1231–3. doi:10.1038/nn1776. PMID   16980962. S2CID   5841202.
47. West, A. B.; et al. (2005). "Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity". Proc Natl Acad Sci U S A. 102 (46): 16842–7. doi: 10.1073/pnas.0507360102 . PMC   1283829 . PMID   16269541.
48. Martin, I.; et al. (2014). "Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease". Cell. 157 (2): 472–485. doi:10.1016/j.cell.2014.01.064. PMC   4040530 . PMID   24725412.
49. Lee, B. D.; et al. (2010). "Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease". Nat Med. 16 (9): 998–1000. doi:10.1038/nm.2199. PMC   2935926 . PMID   20729864.
50. Jeong, G. R.; et al. (2018). "Dysregulated phosphorylation of Rab GTPases by LRRK2 induces neurodegeneration". Mol Neurodegener. 13 (1): 8. doi: 10.1186/s13024-018-0240-1 . PMC   5811984 . PMID   29439717.
51. Mao, X.; et al. (2016). "Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3". Science. 353 (6307): aah3374. doi:10.1126/science.aah3374. PMC   5510615 . PMID   27708076.
52. Yun, S.P.; et al. (2018). "Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease". Nat Med. 24 (7): 931–938. doi:10.1038/s41591-018-0051-5. PMC   6039259 . PMID   29892066.
53. "Ted M. Dawson - Google Scholar Citations". scholar.google.com.
54. "Johns Hopkins Faculty Members Elected Fellows of National Academy of Inventors – JHTV". ventures.jhu.edu.
55. "美国约翰·霍普金斯大学Ted Murray Dawson教授、Valina Lynn Dawson教授受聘为我院荣誉杰出教授". www.xiangya.com.cn.
56. "thedawsonlab". thedawsonlab.