Valina L. Dawson

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Valina L. Dawson (born August 5, 1961) 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, [1] Neuroscience [2] and Physiology. [3] She is a member of the Graduate Program in Cellular and Molecular Medicine and Biochemistry, Cellular and Molecular Biology.

Contents

Biography

Dawson grew up in the Sonoma Valley Wine Country in California. Dawson received her B.S. in environmental toxicology in 1983 from the University of California, Davis. She earned her Ph.D. in pharmacology and toxicology from the University of Utah School of Medicine. Postdoctoral training was conducted at the University of Pennsylvania and the National Institute on Drug Abuse Addiction Research Center. Dawson joined the faculty at Johns Hopkins University School of Medicine in 1994 as an assistant professor in the departments of Neurology, Neuroscience and Physiology. In 2001, she became an associate professor in the departments of Neurology, Neuroscience and Physiology and served as the vice chair of faculty development in the department of Neurology. Dawson was promoted to the position of professor in the departments of Neurology, Neuroscience and Physiology in 2001. In 2002, she founded the Neuroregeneration Program in the Institute of Cell Engineering [4] and became director of the Stem Cell Program in 2009. She was named a Daniel Nathans Innovator in 2017. She served the Society for Neuroscience as a reviewing editor (2003–2009) and then as a senior editor (2010–2016) for the Journal of Neuroscience and is now serving as an advisory board editor for the other society journal, eNeuro . She also served the Society for Neuroscience on the Committee on Women in Neuroscience (2007–2010), professional development committee (2009–2011) and the program committee (2011–2014). She serves on the scientific advisory board of the New York Stem Cell Foundation, the Weill Cornell Burke Medical Research Institute [5] the external advisory board for the Interdepartmental Neuroscience (NUIN) graduate training program at Northwestern University, and the advisory board for NeuroMab. [6] She was a founder of AGY Therapeutics. [7] She is a founder and is on the scientific advisory board of Neuraly and Valted, LLC.

Research

Dawson works closely with her husband and partner, Dr. Ted M. Dawson. Their research studies the molecular mechanisms that lead to neuronal cell death in neurodegenerative diseases, stroke and trauma. They discovered the critical role the gaseous transmitter, nitric oxide (NO), plays in glutamate excitotoxicity [8] [9] and stroke [10] with their postdoctoral mentor, Dr. Solomon H. Snyder. They defined the role for NO generated from neuronal NO synthase or immunologic NO synthase leads in models of HIV dementia [11] [12] and Parkinson's disease. [13] [14] Exploring the signaling cascade led to the identification of peroxynitrite as the nitrogen oxide moiety that mediates neurotoxicity, and the role for poly(ADP-ribose) polymerase (PARP) [15] [16] as the next step in the neurotoxic cascade. They discovered that poly (ADP-ribose) polymer (PAR) is a novel cell death signaling molecule that plays a critical role in neuronal injury. [17] [18] Her research team discovered that PAR leads to cell death by facilitating the release of apoptosis inducing factor (AIF) factor [19] [20] from the mitochondrial surface. [21] Parsylated AIF then recruits macrophage migration inhibitory factor (MIF) and the complex translocates to the nucleus where the nuclease activity of MIF leads to large scale DNA fragmentation. [22] To distinguish this form of cell death from other cell death signaling cascades [23] it was named Parthanatos, for PAR and the Greek god of death, Thanatos. [24] The enzyme that degrades PAR, poly (ADP-ribose) glycohydrolase, is not only an endogenous negative regulator of parthanatos, but required for cell viability. [25] In genetic screens to find cell signals that prevent neurotoxicity, her team discovered an endogenous inhibitor of parthanatos, Iduna (RNF146), a first in class PAR-dependent E3 ligase. [26] [27] In the same screens, Botch was discovered which is an 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 and survival. [28] [29] 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. [30] Genetic variants of Thorase were found in schizophrenic patients. Expression of these variants in mice lead to behavioral deficits that were normalized with the AMPA antagonist Parampenal. [31] Mutations in Thorase leading to gain or loss of function result in lethal developmental disorders in children. [32] [33]

With the discovery of gene mutations that are the cause of rare familial cases of Parkinson's disease, their research team has probed the biologic and pathologic actions of these proteins. They discovered parkin was an E3 ligase that is inactive in patients with genetic mutations in parkin, [34] and that it is also inactive in sporadic Parkinson's disease due to protein modifications by S-nitrosylation [35] and c-Abl tyrosine phosphorylation [36] which led to the discovery of the pathogenic targets, PARIS and AIMP2. [37] PARIS regulates the machinery critical to mitochondrial quality control and thus cell survival. [38] Surprisingly, AIMP2 directly interacts with PARP and activates Parthanatos. [39] Since there are PARP inhibitors in clinical use this finding may provide a new therapeutic target for the treatment of Parkinson's disease. They discovered that DJ-1, which is dysfunctional in Parkinson's disease, is an atypical peroxidoxin-like peroxidase and that its loss of function in PD leads to mitochondrial dysfunction. [40] The Dawson's discovered that mutations in LRRK2 increase its kinase activity [41] [42] and that inhibition of LRRK2 kinase activity is protective in models of Parkinson's disease. [43] The increase in LRRK2 kinase activity leads to enhanced protein translation via the phosphorylation of the ribosomal protein s15. [44] Understanding this shift in the proteome due to altered translation will allow new insight into the alteration in expression of critical proteins that likely underlie the pathogenesis of Parkinson's disease. ArfGAP regulates the GTPase activity of LRRK2 and they discovered that ArfGAP and LRRK2 reciprocally regulate the activity of each other determining neuronal viability. [45] Their labs also discovered that pathologic α-synuclein spreads in the nervous system via engagement with the lymphocyte-activation gene 3 (LAG3). [46] They discovered that Glucagon-like peptide-1 receptor (GLP1R) agonist, NLY01 prevents neuroinflammatory 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. [47] Their work continues to provide critical insights into understanding of the pathogenesis of PD and identify new opportunities for therapies to treat patients with Parkinson's disease. Valina Dawson has published over 400 publications and has an H-index of 129. [48]

Awards

Related Research Articles

<span class="mw-page-title-main">Neurotoxin</span> Toxin harmful to nervous tissue

Neurotoxins are toxins that are destructive to nerve tissue. Neurotoxins are an extensive class of exogenous chemical neurological insults that can adversely affect function in both developing and mature nervous tissue. The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems. Common examples of neurotoxins include lead, ethanol, glutamate, nitric oxide, botulinum toxin, tetanus toxin, and tetrodotoxin. Some substances such as nitric oxide and glutamate are in fact essential for proper function of the body and only exert neurotoxic effects at excessive concentrations.

<span class="mw-page-title-main">Adult neurogenesis</span> Generating of neurons from neural stem cells in adults

Adult neurogenesis is the process in which neurons are generated from neural stem cells in the adult. This process differs from prenatal neurogenesis.

<span class="mw-page-title-main">Parkin (protein)</span>

Parkin is a 465-amino acid residue E3 ubiquitin ligase, a protein that in humans and mice is encoded by the PARK2 gene. Parkin plays a critical role in ubiquitination – the process whereby molecules are covalently labelled with ubiquitin (Ub) and directed towards degradation in proteasomes or lysosomes. Ubiquitination involves the sequential action of three enzymes. First, an E1 ubiquitin-activating enzyme binds to inactive Ub in eukaryotic cells via a thioester bond and mobilises it in an ATP-dependent process. Ub is then transferred to an E2 ubiquitin-conjugating enzyme before being conjugated to the target protein via an E3 ubiquitin ligase. There exists a multitude of E3 ligases, which differ in structure and substrate specificity to allow selective targeting of proteins to intracellular degradation.

<span class="mw-page-title-main">Excitotoxicity</span> Process that kills nerve cells

In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate receptors such as the NMDA receptor or AMPA receptor encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Excess glutamate allows high levels of calcium ions (Ca2+) to enter the cell. Ca2+ influx into cells activates a number of enzymes, including phospholipases, endonucleases, and proteases such as calpain. These enzymes go on to damage cell structures such as components of the cytoskeleton, membrane, and DNA. In evolved, complex adaptive systems such as biological life it must be understood that mechanisms are rarely, if ever, simplistically direct. For example, NMDA in subtoxic amounts induces neuronal survival of otherwise toxic levels of glutamate.

<span class="mw-page-title-main">Poly (ADP-ribose) polymerase</span> Family of proteins

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.

<span class="mw-page-title-main">Neuroprotection</span> Relative preservation of neuronal structure and/or function

Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation. It is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption. Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons. Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms of neuronal injury include decreased delivery of oxygen and glucose to the brain, energy failure, increased levels in oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory changes, iron accumulation, and protein aggregation. Of these mechanisms, neuroprotective treatments often target oxidative stress and excitotoxicity—both of which are highly associated with CNS disorders. Not only can oxidative stress and excitotoxicity trigger neuron cell death but when combined they have synergistic effects that cause even more degradation than on their own. Thus limiting excitotoxicity and oxidative stress is a very important aspect of neuroprotection. Common neuroprotective treatments are glutamate antagonists and antioxidants, which aim to limit excitotoxicity and oxidative stress respectively.

The biochemistry of Alzheimer's disease, the most common cause of dementia, is not yet very well understood. Alzheimer's disease (AD) has been identified as a proteopathy: a protein misfolding disease due to the accumulation of abnormally folded amyloid beta (Aβ) protein in the brain. Amyloid beta is a short peptide that is an abnormal proteolytic byproduct of the transmembrane protein amyloid-beta precursor protein (APP), whose function is unclear but thought to be involved in neuronal development. The presenilins are components of proteolytic complex involved in APP processing and degradation.

<span class="mw-page-title-main">LRRK2</span> Protein kinase found in humans

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.

<span class="mw-page-title-main">PARP1</span> Mammalian protein found in Homo sapiens

Poly [ADP-ribose] polymerase 1 (PARP-1) also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1 is an enzyme that in humans is encoded by the PARP1 gene. It is the most abundant of the PARP family of enzymes, accounting for 90% of the NAD+ used by the family. PARP1 is mostly present in cell nucleus, but cytosolic fraction of this protein was also reported.

<span class="mw-page-title-main">GRIN2A</span> Protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit epsilon-1 is a protein that in humans is encoded by the GRIN2A gene. With 1464 amino acids, the canonical GluN2A subunit isoform is large. GluN2A-short isoforms specific to primates can be produced by alternative splicing and contain 1281 amino acids.

<span class="mw-page-title-main">GRIN1</span> Protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit zeta-1 is a protein that in humans is encoded by the GRIN1 gene.

<span class="mw-page-title-main">ADP-ribosylhydrolase 3</span> Protein-coding gene in the species Homo sapiens

(ADP-ribosyl)hydrolase 3 (ARH3) is an enzyme that in humans is encoded by the ADPRHL2 gene (also called ADPRS). This enzyme reverses the proteins’ post-translational addition of ADP-ribose to serine residues as part of the DNA damage response The enzyme is also known to cleave poly(ADP-ribose) polymers, 1''-O-acetyl-ADP-ribose and alpha-NAD+

In biochemistry, S-nitrosylation is the covalent attachment of a nitric oxide group to a cysteine thiol within a protein to form an S-nitrosothiol (SNO). S-Nitrosylation has diverse regulatory roles in bacteria, yeast and plants and in all mammalian cells. It thus operates as a fundamental mechanism for cellular signaling across phylogeny and accounts for the large part of NO bioactivity.

Parkinson's disease (PD) is a complicated neurodegenerative disease that progresses over time and is marked by bradykinesia, tremor, and stiffness. As the condition worsens, some patients may also experience postural instability. Parkinson's disease (PD) is primarily caused by the gradual degeneration of dopaminergic neurons in the region known as the substantia nigra along with other monoaminergic cell groups throughout the brainstem, increased activation of microglia, and the build-up of Lewy bodies and Lewy neurites, which are proteins found in surviving dopaminergic neurons.

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.

Microglia are the primary immune cells of the central nervous system, similar to peripheral macrophages. They respond to pathogens and injury by changing morphology and migrating to the site of infection/injury, where they destroy pathogens and remove damaged cells.

Ted M. Dawson is an American neurologist and neuroscientist. He is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and Director of the Institute for Cell Engineering at Johns Hopkins University School of Medicine. He has joint appointments in the Department of Neurology, Neuroscience and Department of Pharmacology and Molecular Sciences.

Sonia Gandhi is a British physician and neuroscientist who leads the Francis Crick Institute neurodegeneration laboratory. She holds a joint position at the UCL Queen Square Institute of Neurology. Her research investigates the molecular mechanisms that give rise to Parkinson's disease. During the COVID-19 pandemic, Gandhi was involved with the epidemiological investigations and testing efforts at the Francis Crick Institute.

<span class="mw-page-title-main">SARM1</span> Protein-coding gene in the species Homo sapiens

Sterile alpha and TIR motif containing 1 Is an enzyme that in humans is encoded by the SARM1 gene. It is the most evolutionarily conserved member of the Toll/Interleukin receptor-1 (TIR) family. SARM1's TIR domain has intrinsic NADase enzymatic activity that is highly conserved from archaea, plants, nematode worms, fruit flies, and humans. In mammals, SARM1 is highly expressed in neurons, where it resides in both cell bodies and axons, and can be associated with mitochondria.

<span class="mw-page-title-main">Csaba Szabo (pharmacologist)</span>

Csaba Szabo, a physician and pharmacologist, is the Head of the Pharmacology Section of the University of Fribourg in Switzerland. The Public Library of Science Magazine, PLOS Biology, recognized Szabo in 2019 as one of the most cited researchers in the world.

References

  1. ↑ "Neurology and Neurosurgery". Hopkinsmedicine.org. Retrieved 23 October 2018.
  2. ↑ "The Solomon H Snyder Department of Neuroscience". Neuroscience.jhu.edu. Retrieved 23 October 2018.
  3. ↑ "Department of Physiology". Department of Physiology. Retrieved 23 October 2018.
  4. ↑ "The Johns Hopkins Institute for Cell Engineering (ICE) in Baltimore, Maryland". Hopkinsmedicine.org. Retrieved 23 October 2018.
  5. ↑ "Our Role & Cause". Burke.weill.cornell.edu. Retrieved 23 October 2018.
  6. ↑ "Welcome to NeuroMab!". Neuromab.ucdavis.edu. Retrieved 23 October 2018.
  7. ↑ "AGY Therapeutics Inc". Agyinc.com. Retrieved 23 October 2018.
  8. ↑ Dawson, V.L.; et al. (1991). "Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures". Proc Natl Acad Sci U S A. 88 (14): 6368–6371. Bibcode:1991PNAS...88.6368D. doi: 10.1073/pnas.88.14.6368 . PMC   52084 . PMID   1648740.
  9. ↑ Dawson, V.L.; et al. (1993). "Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures". J. Neurosci. 13 (6): 2651–61. doi: 10.1523/jneurosci.13-06-02651.1993 . PMC   6576487 . PMID   7684776.
  10. ↑ 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.
  11. ↑ Dawson, V.L.; et al. (1993). "Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures". Proc Natl Acad Sci U S A. 90 (8): 3256–3259. Bibcode:1993PNAS...90.3256D. doi: 10.1073/pnas.90.8.3256 . PMC   46278 . PMID   8097316.
  12. ↑ Adamson, D.C.; et al. (1996). "Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1 gp41". Science. 274 (5294): 1917–21. Bibcode:1996Sci...274.1917C. doi:10.1126/science.274.5294.1917. PMID   8943206. S2CID   6122794.
  13. ↑ 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): 4565–4571. Bibcode:1996PNAS...93.4565P. doi: 10.1073/pnas.93.10.4565 . PMC   39317 . PMID   8643444.
  14. ↑ Liberatore, GT; Jackson-Lewis, V; Vukosavic, S; Mandir, AS; Vila, M; McAuliffe, WG; Dawson, VL; Dawson, TM; Przedborski, S (December 1999). "Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease". Nature Medicine. 5 (12): 1403–9. doi:10.1038/70978. PMID   10581083. S2CID   38247532.
  15. ↑ Zhang, J; Dawson, VL; Dawson, TM; Snyder, SH (4 February 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.
  16. ↑ Eliasson, MJ; Sampei, K; Mandir, AS; Hurn, PD; Traystman, RJ; Bao, J; Pieper, A; Wang, ZQ; Dawson, TM; Snyder, SH; Dawson, VL (October 1997). "Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia". Nature Medicine. 3 (10): 1089–95. doi:10.1038/nm1097-1089. PMID   9334719. S2CID   32410245.
  17. ↑ Yu, SW; Andrabi, SA; Wang, H; Kim, NS; Poirier, GG; Dawson, TM; Dawson, VL (28 November 2006). "Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death". Proceedings of the National Academy of Sciences of the United States of America. 103 (48): 18314–9. Bibcode:2006PNAS..10318314Y. doi: 10.1073/pnas.0606528103 . PMC   1838748 . PMID   17116881.
  18. ↑ Andrabi, SA; Kim, NS; Yu, SW; Wang, H; Koh, DW; Sasaki, M; Klaus, JA; Otsuka, T; Zhang, Z; Koehler, RC; Hurn, PD; Poirier, GG; Dawson, VL; Dawson, TM (28 November 2006). "Poly(ADP-ribose) (PAR) polymer is a death signal". Proceedings of the National Academy of Sciences of the United States of America. 103 (48): 18308–13. Bibcode:2006PNAS..10318308A. doi: 10.1073/pnas.0606526103 . PMC   1838747 . PMID   17116882.
  19. ↑ Yu, SW; Wang, H; Poitras, MF; Coombs, C; Bowers, WJ; Federoff, HJ; Poirier, GG; Dawson, TM; Dawson, VL (12 July 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.
  20. ↑ Wang, Y; Kim, NS; Haince, JF; Kang, HC; David, KK; Andrabi, SA; Poirier, GG; Dawson, VL; Dawson, TM (5 April 2011). "Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos)". Science Signaling. 4 (167): ra20. doi:10.1126/scisignal.2000902. PMC   3086524 . PMID   21467298.
  21. ↑ Yu, SW; Wang, Y; Frydenlund, DS; Ottersen, OP; Dawson, VL; Dawson, TM (18 November 2009). "Outer mitochondrial membrane localization of apoptosis-inducing factor: mechanistic implications for release". ASN Neuro. 1 (5): AN20090046. doi:10.1042/AN20090046. PMC   2784601 . PMID   19863494.
  22. ↑ Wang, Y; An, R; Umanah, GK; Park, H; Nambiar, K; Eacker, SM; Kim, B; Bao, L; Harraz, MM; Chang, C; Chen, R; Wang, JE; Kam, TI; Jeong, JS; Xie, Z; Neifert, S; Qian, J; Andrabi, SA; Blackshaw, S; Zhu, H; Song, H; Ming, GL; Dawson, VL; Dawson, TM (7 October 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.
  23. ↑ Galluzzi, L; et al. (March 2018). "Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018". Cell Death and Differentiation. 25 (3): 486–541. doi:10.1038/s41418-017-0012-4. hdl:1721.1/116948. PMC   5864239 . PMID   29362479.
  24. ↑ David, KK; Andrabi, SA; Dawson, TM; Dawson, VL (1 January 2009). "Parthanatos, a messenger of death". Frontiers in Bioscience (Landmark Edition). 14 (14): 1116–28. doi:10.2741/3297. PMC   4450718 . PMID   19273119.
  25. ↑ Koh, DW; Lawler, AM; Poitras, MF; Sasaki, M; Wattler, S; Nehls, MC; Stöger, T; Poirier, GG; Dawson, VL; Dawson, TM (21 December 2004). "Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality". Proceedings of the National Academy of Sciences of the United States of America. 101 (51): 17699–704. Bibcode:2004PNAS..10117699K. doi: 10.1073/pnas.0406182101 . PMC   539714 . PMID   15591342.
  26. ↑ Andrabi, SA; Kang, HC; Haince, JF; Lee, YI; Zhang, J; Chi, Z; West, AB; Koehler, RC; Poirier, GG; Dawson, TM; Dawson, VL (June 2011). "Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death". Nature Medicine. 17 (6): 692–9. doi:10.1038/nm.2387. PMC   3709257 . PMID   21602803.
  27. ↑ Kang, HC; Lee, YI; Shin, JH; Andrabi, SA; Chi, Z; Gagné, JP; Lee, Y; Ko, HS; Lee, BD; Poirier, GG; Dawson, VL; Dawson, TM (23 August 2011). "Iduna is a poly(ADP-ribose) (PAR)-dependent E3 ubiquitin ligase that regulates DNA damage". Proceedings of the National Academy of Sciences of the United States of America. 108 (34): 14103–8. Bibcode:2011PNAS..10814103K. doi: 10.1073/pnas.1108799108 . PMC   3161609 . PMID   21825151.
  28. ↑ Chi, Z; Zhang, J; Tokunaga, A; Harraz, MM; Byrne, ST; Dolinko, A; Xu, J; Blackshaw, S; Gaiano, N; Dawson, TM; Dawson, VL (17 April 2012). "Botch promotes neurogenesis by antagonizing Notch". Developmental Cell. 22 (4): 707–20. doi:10.1016/j.devcel.2012.02.011. PMC   3331935 . PMID   22445366.
  29. ↑ 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 (8 May 2014). "Botch is a γ-glutamyl cyclotransferase that deglycinates and antagonizes Notch". Cell Reports. 7 (3): 681–8. doi:10.1016/j.celrep.2014.03.048. PMC   4031649 . PMID   24767995.
  30. ↑ Zhang, J; Wang, Y; Chi, Z; Keuss, MJ; Pai, YM; Kang, HC; Shin, JH; Bugayenko, A; Wang, H; Xiong, Y; Pletnikov, MV; Mattson, MP; Dawson, TM; Dawson, VL (15 April 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.
  31. ↑ Umanah, GKE; et al. (13 December 2017). "Thorase variants are associated with defects in glutamatergic neurotransmission that can be rescued by Perampanel". Science Translational Medicine. 9 (420): eaah4985. doi:10.1126/scitranslmed.aah4985. PMC   6573025 . PMID   29237760.
  32. ↑ Ahrens-Nicklas, RC; Umanah, GK; Sondheimer, N; Deardorff, MA; Wilkens, AB; Conlin, LK; Santani, AB; Nesbitt, A; Juulsola, J; Ma, E; Dawson, TM; Dawson, VL; Marsh, ED (February 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.
  33. ↑ Piard, J; et al. (30 January 2018). "A homozygous ATAD1 mutation impairs postsynaptic AMPA receptor trafficking and causes a lethal encephalopathy". Brain: A Journal of Neurology. 141 (3): 651–661. doi:10.1093/brain/awx377. PMC   5837721 . PMID   29390050.
  34. ↑ Zhang, Y; Gao, J; Chung, KK; Huang, H; Dawson, VL; Dawson, TM (21 November 2000). "Parkin functions as an E2-dependent ubiquitin- protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (24): 13354–9. Bibcode:2000PNAS...9713354Z. doi: 10.1073/pnas.240347797 . PMC   27228 . PMID   11078524.
  35. ↑ Chung, KK; Thomas, B; Li, X; Pletnikova, O; Troncoso, JC; Marsh, L; Dawson, VL; Dawson, TM (28 May 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.
  36. ↑ Ko, HS; Lee, Y; Shin, JH; Karuppagounder, SS; Gadad, BS; Koleske, AJ; Pletnikova, O; Troncoso, JC; Dawson, VL; Dawson, TM (21 September 2010). "Phosphorylation by the c-Abl protein tyrosine kinase inhibits parkin's ubiquitination and protective function". Proceedings of the National Academy of Sciences of the United States of America. 107 (38): 16691–6. Bibcode:2010PNAS..10716691K. doi: 10.1073/pnas.1006083107 . PMC   2944759 . PMID   20823226.
  37. ↑ Ko, HS; von Coelln, R; Sriram, SR; Kim, SW; Chung, KK; Pletnikova, O; Troncoso, J; Johnson, B; Saffary, R; Goh, EL; Song, H; Park, BJ; Kim, MJ; Kim, S; Dawson, VL; Dawson, TM (31 August 2005). "Accumulation of the authentic parkin substrate aminoacyl-tRNA synthetase cofactor, p38/JTV-1, leads to catecholaminergic cell death". The Journal of Neuroscience. 25 (35): 7968–78. doi:10.1523/JNEUROSCI.2172-05.2005. PMC   6725452 . PMID   16135753.
  38. ↑ Shin, JH; Ko, HS; Kang, H; Lee, Y; Lee, YI; Pletinkova, O; Troconso, JC; Dawson, VL; Dawson, TM (4 March 2011). "PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson's disease". Cell. 144 (5): 689–702. doi:10.1016/j.cell.2011.02.010. PMC   3063894 . PMID   21376232.
  39. ↑ Lee, Y; Karuppagounder, SS; Shin, JH; Lee, YI; Ko, HS; Swing, D; Jiang, H; Kang, SU; Lee, BD; Kang, HC; Kim, D; Tessarollo, L; Dawson, VL; Dawson, TM (October 2013). "Parthanatos mediates AIMP2-activated age-dependent dopaminergic neuronal loss". Nature Neuroscience. 16 (10): 1392–400. doi:10.1038/nn.3500. PMC   3785563 . PMID   23974709.
  40. ↑ Andres-Mateos, E; Perier, C; Zhang, L; Blanchard-Fillion, B; Greco, TM; Thomas, B; Ko, HS; Sasaki, M; Ischiropoulos, H; Przedborski, S; Dawson, TM; Dawson, VL (11 September 2007). "DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase". Proceedings of the National Academy of Sciences of the United States of America. 104 (37): 14807–12. Bibcode:2007PNAS..10414807A. doi: 10.1073/pnas.0703219104 . PMC   1976193 . PMID   17766438.
  41. ↑ West, AB; Moore, DJ; Biskup, S; Bugayenko, A; Smith, WW; Ross, CA; Dawson, VL; Dawson, TM (15 November 2005). "Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity". Proceedings of the National Academy of Sciences of the United States of America. 102 (46): 16842–7. doi: 10.1073/pnas.0507360102 . PMC   1283829 . PMID   16269541.
  42. ↑ Smith, WW; Pei, Z; Jiang, H; Moore, DJ; Liang, Y; West, AB; Dawson, VL; Dawson, TM; Ross, CA (20 December 2005). "Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration". Proceedings of the National Academy of Sciences of the United States of America. 102 (51): 18676–81. Bibcode:2005PNAS..10218676S. doi: 10.1073/pnas.0508052102 . PMC   1317945 . PMID   16352719.
  43. ↑ Lee, BD; Shin, JH; VanKampen, J; Petrucelli, L; West, AB; Ko, HS; Lee, YI; Maguire-Zeiss, KA; Bowers, WJ; Federoff, HJ; Dawson, VL; Dawson, TM (September 2010). "Inhibitors of leucine-rich repeat kinase-2 protect against models of Parkinson's disease". Nature Medicine. 16 (9): 998–1000. doi:10.1038/nm.2199. PMC   2935926 . PMID   20729864.
  44. ↑ Martin, I; et al. (10 April 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.
  45. ↑ Xiong, Y; Yuan, C; Chen, R; Dawson, TM; Dawson, VL (14 March 2012). "ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2". The Journal of Neuroscience. 32 (11): 3877–86. doi:10.1523/JNEUROSCI.4566-11.2012. PMC   3319331 . PMID   22423108.
  46. ↑ Mao, X; et al. (30 September 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.
  47. ↑ 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.
  48. ↑ "Valina L. Dawson - Google Scholar Citations". Scholar.google.com. Retrieved 23 October 2018.
  49. ↑ "Valina L. Dawson received the 2019 Debrecen Award for Molecular Medicine". unideb.hu. Retrieved 27 November 2019.
  50. ↑ "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". Xiangya.com.cn. Retrieved 23 October 2018.
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