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Stephen Waxman

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Stephen G. Waxman is an American neurologist and neuroscientist.[1] He served as Chairman of the Department of Neurology at Yale Medical School, and Neurologist-in-Chief at Yale-New Haven Hospital from 1986 until 2009.[2] As of 2018, he is the Bridget Flaherty Professor of Neurology, Neurobiology, and Pharmacology at Yale University.[1] He founded the Yale University Neuroscience & Regeneration Research Center in 1988 and is its Director.[3] He previously held faculty positions at Harvard Medical School, MIT, and Stanford Medical School.[2][4] He is also visiting professor at University College London.[5]

Waxman has built on the "molecular revolution" to study, at a fundamental level, how neurons and glial cells work within the normal nervous system, and why they do not work properly in various diseased states. His laboratory studies isolated nerve cells in culture,[6] and rodents with experimental autoimmune encephalomyelitis, a model of multiple sclerosis.[7] These studies have, for example, provided a basis for a clinical trial of the efficacy of phenytoin, a sodium channel blocker in patients with optic neuritis.[8]. Waxman's studies combine molecular genetics, molecular biology, and biophysics to show how specific ion channels relate to human pain.[9] He has been a member of an international coalition that showed that sodium channel mutations can cause of peripheral neuropathy.[10] He has used atomic-level modeling to study pharmacogenomics, at first in laboratory studies,[11] and has carried out early studies on genomically guided approaches to the treatment of pain.[12] A novel class of medications that target sodium channels in the peripheral nervous system, and that do not have potential for addiction, is based in part on his work and is currently being assessed in early-stage clinical trials. [13][14]

Biography

Waxman was born on August 17, 1945 in Newark, NJ, to Morris Waxman, a court reporter, and Beatrice Waxman. His BA was from Harvard (1967), and his MD (1971) and PhD (1972) degrees were from the Albert Einstein College of Medicine.[1] Following a residency in the Harvard Neurology Unit at Boston City Hospital, he joined the faculty of Harvard Medical School and MIT where he served, respectively, as Assistant Professor of Neurology and Visiting Assistant Professor of Biology from 1975 to 1977, then as Associate Professor of Neurology and Visiting Associate Professor of Biology from 1977 to 1978.[2] He moved to Stanford Medical School as Professor of Neurology in 1978 and, at Stanford, served as Chairman of the Neuroscience Program and Associate Chairman of Neurology.[4] He moved to Yale Medical School in 1986.[1]

Research

Waxman's early research examined the design principles of axons and defined the mechanism by which myelin insures rapid conduction of impulses along nerve fibers within the brain and spinal cord.[15]. He used electron microscopy, immunocytochemistry and electrophysiological methods to study the complex distribution of sodium and potassium channels along myelinated nerve fibers, and he subsequently investigated how this complex ion channel architecture is important for the transmission of nerve impulses along healthy nerve fibers, and after demyelination as occurs in multiple sclerosis.[16] He also showed that there is plasticity of the axon membrane in demyelinated nerve fibers, with myelin-poor axons having more sodium channels.[17][18]. This molecular remodeling supports recovery of impulse conduction that underlies remissions in multiple sclerosis. Together with Peter Stys and Bruce Ransom, he studied the role of sodium channels in the degeneration of axons,[6] and he went on to study the molecular identities of the sodium channels involved in axonal injury.[18]

He continues to research the molecular basis for pain after nerve injury. In a set of studies that combined molecular genetics, molecular biology and biophysics, he assessed the contribution of specific types of sodium channels to pain, both in experimental models, and also in the clinic.[19][9] These studies identified sodium channel Nav1.7 as a "volume knob" on pain-signaling neurons. Waxman was part of an international coalition that identified mutations in sodium channels predicted to cause common peripheral neuropathies.[10] He has investigated how a "precision medicine" approach can be applied to the treatment of pain, first in studies that used atomic-level modeling to advance pharmacogenomics in the laboratory,[11] and then in the clinic in a translational medicine approach;[12] these studies have been reviewed in an editorial in JAMA Neurology that stated "there are still relatively few examples in medicine where the molecular reasoning has been rewarded with a comparable degree of success".[20] A new class of medications targeting peripheral sodium channels, with no potential for addiction, is based in part on Waxman's work, and is currently being assessed in Phase II clinical trials.[13][14]

Publications and editorial work

Waxman has published more than 700 scientific papers.[citation needed] He has edited nine books on various aspects of neurology and neuroscience, and is the author of two textbooks, Spinal Cord Compression: Diagnosis and Principles of Management (with Thomas N. Byrne),[21] and Clinical Neuroanatomy (which has been translated into eight languages),[22] as well as the popular book, Chasing Men on Fire: The Story of the Search for a Pain Gene, which recounts his and others' research into the genetic basis of pain.[23][24]

As of 2018, he is the Editor-in-Chief of The Neuroscientist[25] and Neuroscience Letters,[26] and has also been editorial board member of Annals of Neurology, Brain, The Journal of Physiology, Nature Reviews Neurology, Trends in Molecular Medicine, and Trends in Neurosciences.

Awards

In 1996 Waxman was elected to the National Academy of Medicine.[27] His honors include the Tuve Award (NIH),[28] the Distinguished Alumnus Award (Albert Einstein College of Medicine),[29] the Dystel Prize and the Wartenberg Award (American Academy of Neurology),[30] the Middleton Award[31] and the Magnuson Award (Veterans Administration),[32] the Soriano Award (American Neurological Association),[33] and the British Physiological Society's Annual Prize.[34]

References

  1. ^ a b c d "Stephen George Waxman, MD, PhD > Neurology | Yale School of Medicine". medicine.yale.edu. Retrieved 2018-03-22.
  2. ^ a b c G., Waxman, Stephen (2001). Form and function in the brain and spinal cord : perspectives of a neurologist. Cambridge, Mass.: MIT Press. ISBN 0262232103. OCLC 43362046.{{cite book}}: CS1 maint: multiple names: authors list (link)
  3. ^ "Home > Center for Neuroscience and Regeneration Research | Yale School of Medicine". medicine.yale.edu. Retrieved 2018-03-22.
  4. ^ a b "About | Neurosciences PhD Program | Stanford Medicine". med.stanford.edu. Retrieved 2018-03-22.
  5. ^ "Stephen Waxman, MD, PhD | Yale and the World". world.yale.edu. Retrieved 2018-03-22.
  6. ^ a b Stys, P. K.; Waxman, S. G.; Ransom, B. R. (February 1992). "Ionic mechanisms of anoxic injury in mammalian CNS white matter: role of Na+ channels and Na(+)-Ca2+ exchanger". The Journal of Neuroscience: the Official Journal of the Society for Neuroscience. 12 (2): 430–439. ISSN 0270-6474. PMID 1311030.
  7. ^ Lo, Albert C.; Saab, Carl Y.; Black, Joel A.; Waxman, Stephen G. (November 2003). "Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo". Journal of Neurophysiology. 90 (5): 3566–3571. doi:10.1152/jn.00434.2003. ISSN 0022-3077. PMID 12904334.
  8. ^ Raftopoulos, Rhian; Hickman, Simon J.; Toosy, Ahmed; Sharrack, Basil; Mallik, Shahrukh; Paling, David; Altmann, Daniel R.; Yiannakas, Marios C.; Malladi, Prasad (March 2016). "Phenytoin for neuroprotection in patients with acute optic neuritis: a randomised, placebo-controlled, phase 2 trial". The Lancet. Neurology. 15 (3): 259–269. doi:10.1016/S1474-4422(16)00004-1. ISSN 1474-4465. PMID 26822749.
  9. ^ a b Waxman, Stephen G.; Dib-Hajj, Sulayman (December 2005). "Erythermalgia: molecular basis for an inherited pain syndrome". Trends in Molecular Medicine. 11 (12): 555–562. doi:10.1016/j.molmed.2005.10.004. ISSN 1471-4914. PMID 16278094.
  10. ^ a b Faber, Catharina G.; Lauria, Giuseppe; Merkies, Ingemar S. J.; Cheng, Xiaoyang; Han, Chongyang; Ahn, Hye-Sook; Persson, Anna-Karin; Hoeijmakers, Janneke G. J.; Gerrits, Monique M. (2012-11-20). "Gain-of-function Nav1.8 mutations in painful neuropathy". Proceedings of the National Academy of Sciences of the United States of America. 109 (47): 19444–19449. doi:10.1073/pnas.1216080109. ISSN 1091-6490. PMC 3511073. PMID 23115331.{{cite journal}}: CS1 maint: PMC format (link)
  11. ^ a b Yang, Yang; Dib-Hajj, Sulayman D.; Zhang, Jian; Zhang, Yang; Tyrrell, Lynda; Estacion, Mark; Waxman, Stephen G. (2012). "Structural modelling and mutant cycle analysis predict pharmacoresponsiveness of a Na(V)1.7 mutant channel". Nature Communications. 3: 1186. doi:10.1038/ncomms2184. ISSN 2041-1723. PMC 3530897. PMID 23149731.{{cite journal}}: CS1 maint: PMC format (link)
  12. ^ a b Geha, Paul; Yang, Yang; Estacion, Mark; Schulman, Betsy R.; Tokuno, Hajime; Apkarian, A. Vania; Dib-Hajj, Sulayman D.; Waxman, Stephen G. (2016-06-01). "Pharmacotherapy for Pain in a Family With Inherited Erythromelalgia Guided by Genomic Analysis and Functional Profiling". JAMA neurology. 73 (6): 659–667. doi:10.1001/jamaneurol.2016.0389. ISSN 2168-6157. PMID 27088781.
  13. ^ a b Cao, Lishuang; McDonnell, Aoibhinn; Nitzsche, Anja; Alexandrou, Aristos; Saintot, Pierre-Philippe; Loucif, Alexandre J. C.; Brown, Adam R.; Young, Gareth; Mis, Malgorzata (04-20-2016). "Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia". Science Translational Medicine. 8 (335): 335ra56. doi:10.1126/scitranslmed.aad7653. ISSN 1946-6242. PMID 27099175. {{cite journal}}: Check date values in: |date= (help)
  14. ^ a b Zakrzewska, Joanna M.; Palmer, Joanne; Morisset, Valerie; Giblin, Gerard Mp; Obermann, Mark; Ettlin, Dominik A.; Cruccu, Giorgio; Bendtsen, Lars; Estacion, Mark (April 2017). "Safety and efficacy of a Nav1.7 selective sodium channel blocker in patients with trigeminal neuralgia: a double-blind, placebo-controlled, randomised withdrawal phase 2a trial". The Lancet. Neurology. 16 (4): 291–300. doi:10.1016/S1474-4422(17)30005-4. ISSN 1474-4465. PMID 28216232.
  15. ^ Waxman, SG; Bennett, MV (16 August 1972). "Relative conduction velocities of small myelinated and non-myelinated fibres in the central nervous system". Nature: New biology. 238 (85): 217–9. PMID 4506206.
  16. ^ Waxman, SG; Ritchie, JM (28 June 1985). "Organization of ion channels in the myelinated nerve fiber". Science. 228 (4707): 1502–7. PMID 2409596.
  17. ^ Waxman, SG (24 June 1982). "Membranes, myelin, and the pathophysiology of multiple sclerosis". The New England journal of medicine. 306 (25): 1529–33. doi:10.1056/NEJM198206243062505. PMID 7043271.
  18. ^ a b Craner, MJ; Newcombe, J; Black, JA; Hartle, C; Cuzner, ML; Waxman, SG (25 May 2004). "Molecular changes in neurons in multiple sclerosis: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger". Proceedings of the National Academy of Sciences of the United States of America. 101 (21): 8168–73. doi:10.1073/pnas.0402765101. PMID 15148385.
  19. ^ Rush, AM; Dib-Hajj, SD; Liu, S; Cummins, TR; Black, JA; Waxman, SG (23 May 2006). "A single sodium channel mutation produces hyper- or hypoexcitability in different types of neurons". Proceedings of the National Academy of Sciences of the United States of America. 103 (21): 8245–50. doi:10.1073/pnas.0602813103. PMID 16702558.
  20. ^ Pascual, JM (1 June 2016). "Understanding Atomic Interactions to Achieve Well-being". JAMA Neurology. 73 (6): 626–7. doi:10.1001/jamaneurol.2016.0546. PMID 27089464.
  21. ^ N., Byrne, Thomas (1990). Spinal cord compression : diagnosis and principles of management. Waxman, Stephen G. Philadelphia: F.A. Davis. ISBN 9780803614659. OCLC 21335109.{{cite book}}: CS1 maint: multiple names: authors list (link)
  22. ^ G.,, Waxman, Stephen. Clinical neuroanatomy. Preceded by: Waxman, Stephen G. (Twenty-eighth ed.). New York. ISBN 9780071847704. OCLC 967782029.{{cite book}}: CS1 maint: extra punctuation (link) CS1 maint: multiple names: authors list (link)
  23. ^ G., Waxman, Stephen (2018). Chasing Men on Fire : the Story of the Search for a Pain Gene. Cambridge, MA: The MIT Press. ISBN 9780262037402. OCLC 1028188541.{{cite book}}: CS1 maint: multiple names: authors list (link)
  24. ^ Tor Wager (2018). "The long search for the pain gene". Nature. 556: 308. doi:10.1038/d41586-018-04560-z.
  25. ^ "The Neuroscientist | SAGE Publications Inc". us.sagepub.com. Retrieved 2018-03-22.
  26. ^ Neuroscience Letters.
  27. ^ "Member - National Academy of Medicine". National Academy of Medicine. Retrieved 2018-03-22.
  28. ^ "US News Dr. Stephen Waxman, Neurology". {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  29. ^ "STEPHEN G. WAXMAN, M.D., PH.D | Alumni | Albert Einstein College of Medicine". www.einstein.yu.edu. Retrieved 2018-03-22.
  30. ^ "John Dystal Prize". {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  31. ^ "VA BLR&D Research Awards". www.research.va.gov. Retrieved 2018-03-22.
  32. ^ "VA RR&D Magnuson Award 2012". {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  33. ^ "Soriano Lectureship | American Neurological Association (ANA)". myana.org. Retrieved 2018-03-22.
  34. ^ Waxman, SG (2009). "Fire, Fantoms and Fugu: Sodium Channels from Squid to Clinic - The Physiological Society Annual Review Prize Lecture". Proceedings of the Physiological Society. Proc Physiol Soc 15. ISSN 1749-6187.

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