Stephen Waxman
Stephen G. Waxman | |
---|---|
MIT (1975-1978) |
Stephen George Waxman (born 1945) is an American
Early life and education
Stephen Waxman was born on August 17, 1945, and grew up in Newark, New Jersey. His father was a court reporter and his mother a housewife. Waxman received his BA from
Research
Stephen Waxman became interested in
Following medical school, a Ph.D. degree, internship and residency in neurology, Waxman turned his focus to nerve injury and to
Building on his interest in nerve injury and his expertise on sodium channels, Waxman made a series of important discoveries about pain after injury to the nervous system. He was the first to show that after nerve injury, the damaged nerve cells send erroneous pain signals to the brain because they turn on the genes for the wrong types of sodium channels,[12] a phenomenon that Waxman likened to “putting type D batteries into a portable radio that needs AA batteries”. These studies provided a major clue to understanding neuropathic pain.
Waxman’s next major studies – carried out at a time when the opiate epidemic was causing deaths around the country – helped to propel the search for new, non-addictive
As part of his push to understand these peripheral channels and the
Waxman was particularly proud of a study in which he used atomic-level modeling to advance pharmacogenomics[20] in a paper that was accompanied by an editorial stating “there are still relatively few examples in medicine where molecular reasoning has been rewarded with a comparable degree of success”.[21] He used computer modeling to assess the ways that different ion channels collaborate like members of a symphony to modulate the messaging of pain-signaling neurons. Waxman also studied why some individuals seem to tolerate pain better than others. Using human stem cells to model painful disease, Waxman pinpointed several “pain resilience” genes.[22] Waxman’s studies propelled a generation of clinical studies on a new class of medications aimed at relieving pain by blocking Nav1.7 and Nav1.8.[23][24]
Awards and distinctions
Waxman has been the recipient of many distinctions:[25]
- 1973 - Trygve Tuve Memorial Award for Outstanding Contributions in the Biomedical Sciences, NIH
- 1975 - Research Career Development Award, NINCDS
- 1987 - Established Investigator, National Multiple Sclerosis Society
- 1991 - Distinguished Alumnus Award, Albert Einstein College of Medicine
- 1991 - Fellow, Royal Society of Medicine
- 1993 - Member, Dana Alliance for Brain Initiatives
- 1994 - Listed in The Best Doctors in America.
- 1995 - The Adrian Lecture (Xth International Congress of Clinical Neurophysiology)
- 1996 - Elected to Institute of Medicine, National Academy of Sciences
- 1999 - Landmark Award for Biomedical Research
- 1999 - Wartenberg Award, American Academy of Neurology
- 1999 - Honorary Senior Fellow, Institute of Neurology, London
- 2000 - Dystel Prize for Research on Multiple Sclerosis, American Academy of Neurology/NMSS
- 2004 - Reingold Award, National Multiple Sclerosis Society
- 2005 - Honorary Member, Association of British Neurologists
- 2009 - W.I. McDonald Award, British Multiple Sclerosis Society
- 2009 - William S Middleton Award (highest scientific honor of the U.S. Capitol).
- 2009 - Annual Review Prize, A.L. Hodgkin)
- 2013 - Paul B. Magnuson Award for Outstanding Achievement in Rehabilitation Research, U.S. Department of Veterans Affairs
- 2013 - American Neurological Assoc/Annals of Neurology Prize for Distinguished Contribution to Clinical Neuroscience
- 2014 - Soriano Award, American Neurological Association
- 2018 - Julius Axelrod Prize, Society for Neuroscience
Selected Publications
Kriebel, M. E., Bennett, M. V. L., Waxman, S. G. and Pappas, G. D. Oculomotor neurons in fish: electrotonic coupling and multiple sites of impulse initiation. Science, 166:520-524, 1969. doi:10.1126/science.166.3904.520 PMID: 4309628
Waxman, S. G. Closely spaced nodes of Ranvier in the teleost brain. Nature, 227:283-284, 1970. doi:10.1038/227283a0 PMID: 5428197
Waxman, S. G. and Bennett, M. V. L. Relative conduction velocities of small myelinated and non- myelinated fibers in the central nervous system. Nature New Biology, 238:217-219, 1972. doi:10.1038/newbio238217a0 PMID: 4506206
Waxman, S. G. and Geschwind, N. Hypergraphia in temporal lobe epilepsy. Neurology, 14:629- 637, 1974. (reprinted in: Epilepsy and Behav, 6:282-91, 2005). doi:10.1016/j.yebeh.2004.11.022 PMID: 15710320
Swadlow, H. A. and Waxman, S. G. Observations on impulse conduction along central axons. Proceedings of the National Academy of Sciences – U.S.A., 72:5156-5159, 1975. doi:10.1073/pnas.72.12.5156 PMID: 1061101
Waxman, S. G. Prerequisites for conduction in demyelinated fibers. Neurology, 28:27-34, 1978. doi:10.1212/wnl.28.9_part_2.27 PMID: 568749
Swadlow, H. A., Geschwind, N. and Waxman, S. G. Commissural transmission in humans. Science, 204:530-531, 1979. doi:10.1126/science.432661 PMID 432661
Foster, R. E., Whalen, C. C. and Waxman, S. G. Reorganization of the axonal membrane of demyelinated nerve fibers: morphological evidence. Science, 210:661-663, 1980. doi:10.1126/science.6159685 PMID: 6159685
Kocsis, J. D. and Waxman, S. G. Absence of potassium conductance in central myelinated axons. Nature, 287:348-349, 1980. doi:10.1038/287348a0 PMID: 7421994
Malenka, R. C., Kocsis, J. D., Ransom, B. R. and Waxman, S. G. Modulation of parallel fiber excitability by postsynaptically mediated changes in extracellular potassium. Science, 214:339-341, 1981. doi:10.1126/science.7280695 PMID: 7280695
Waxman, S. G. Current concepts in neurology: membranes, myelin and the pathophysiology of multiple sclerosis. New England Journal of Medicine, 306:1529-1533, 1982. doi:10.1056/NEJM198206243062505 PMID: 7043271
Kocsis, J. D. and Waxman, S. G. Long-term regenerated nerve fibres retain sensitivity to potassium channel blocking agents. Nature, 304:640-642, 1983. doi:10.1038/304640a0 PMID: 6308475
Waxman, S. G. and Ritchie, J. M. Organization of ion channels in the myelinated nerve fiber. Science, 228:1502-1507, 1985. doi:10.1126/science.2409596 PMID: 2409596
Stys, P. K., Ransom, B. R., Waxman, S. G. and Davis, P. K. Role of extracellular calcium in anoxic injury of mammalian central white matter. Proceedings of the National Academy of Sciences – U.S.A., 87:4212-4216, 1990. doi:10.1073/pnas.87.11.4212 PMID: 2349231
Stys, P.K., Waxman, S.G. and Ransom, B.R. Ionic mechanisms of anoxic injury in mammalian CNS white matter: Role of Na+ channels and Na+-Ca2+ exchanger. Journal of Neuroscience, 12:430-439, 1992. doi:10.1523/JNEUROSCI.12-02-00430.1992 PMID: 1311030
Stys, P.K., Sontheimer, H., Ransom, B.R. and Waxman, S.G. Non-inactivating, TTX-sensitive Na+ conductance in rat optic nerve axons. Proceedings of the National Academy of Sciences – U.S.A., 90:6976-6980, 1993. doi:10.1073/pnas.90.15.6976 PMID: 8394004
Waxman, S.G., Kocsis, J.D. and Black, J.A. Type III sodium channel mRNA is expressed in embryonic but not adult spinal sensory neurons, and is re-expressed following axotomy. Journal of Neurophysiology, 72:466-471,1994. doi:10.1152/jn.1994.72.1.466 PMID: 7965028
Utzschneider, D.A., Archer, D.R., Kocsis, J.D., Waxman, S.G. and Duncan, I.D. Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat. Proceedings of the National Academy of Sciences – U.S.A., 91:53-57, 1994. doi:10.1073/pnas.91.1.53 PMID: 8278406
Waxman, S.G. Demyelinating diseases: New pathological insights, new therapeutic targets. New England Journal of Medicine, 338:323-325, 1998. doi:10.1073/pnas.91.1.53 PMID: 9445415
Dib-Hajj, S.D., Tyrrell, L., Black, J.A., Waxman, S.G. NaN, a novel voltage-gated Na channel preferentially expressed in peripheral sensory neurons and down-regulated following axotomy. Proceedings of the National Academy of Sciences – U.S.A., 95:8963-8968, 1998. doi:10.1073/pnas.95.15.8963 PMID: 9671787
Tanaka, M., Cummins, T.R., Ishikawa, K., Black, J.A., Ibata, Y., Waxman, S.G. Molecular and functional remodeling of electrogenic membrane of hypothalamic neurons in response to changes in their input. Proceedings of the National Academy of Sciences – U.S.A., 96:1088-1093, 1999. doi:10.1073/pnas.96.3.1088 PMID: 9927698
Black, J. A., Dib-Hajj, S., Baker, D., Newcombe, J., Cuzner, M. L., Waxman, S. G. Sensory neuron specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis. Proceedings of the National Academy of Sciences – U.S.A., 97: 11598-11602, 2000. doi:10.1073/pnas.97.21.11598 PMID: 11027357
Waxman, S. G. Transcriptional channelopathies: an emerging class of disorders. Nature Reviews – Neuroscience, 2: 652-659, 2001. doi:10.1038/35090026 PMID: 11533733
Craner, M.J., Newcombe, J., Black, J.A., Hartle, C., Cuzner, M.L., Waxman, S.G. Molecular changes in neurons in MS: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+ /Ca2+ exchanger. Proceedings of the National Academy of Sciences – U.S.A., 101: 8168-8173, 2004. doi:10.1073/pnas.0402765101 PMID: 15148385
Dib-Hajj, S.D., Rush, A.M., Cummins, T.R., Hisama, F.M., Novella, S., Tyrrell, L., Marshall, L., Waxman, S.G. Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons. Brain, 128:1847-1854, 2005. doi:10.1093/brain/awh514 PMID: 15958509
Waxman, S.G., Dib-Hajj, S.D. Erythermalgia: molecular basis for an inherited pain syndrome. Trends in Molecular Medicine, 11 (12): 555-562, 2005. doi:10.1016/j.molmed.2005.10.004 PMID: 16278094
Waxman, S.G. Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nature Reviews – Neuroscience, 5: 932-942 (2006). doi:10.1038/nrn2023 PMID: 17115075
Waxman, S.G. A channel sets the gain on pain. Nature, 444: 831-832, 2006. doi:10.1038/444831a PMID: 17167466
Rush, A.M., Dib-Hajj, S.D., Liu, S., Cummins, T.R, Black, J.A., Waxman, S.G. A single sodium channel mutation produces hyper-or hypoexcitability in different types of neurons. Proceedings of the National Academy of Sciences – U.S.A., 103: 8245-8250, 2006. doi:10.1073/pnas.0602813103 PMID: 16702558
Waxman, S.G. Channel, neuronal, and clinical function in sodium channelopathies: From genotype to phenotype. Nature Neuroscience, 10:405-410, 2007. doi:10.1038/nn1857 PMID: 17387329
Waxman, S.G. Sodium channels and neuroprotection in MS: current status. Nature Clinical Neurology, 4:159-170, 2008. doi:10.1038/ncpneuro0735 PMID: 18227822
Faber, C.G., Hoeijmakers, J.G.J., Ahn, H.S., Cheng, X, Han, C., Choi, J.S., Estacion, M., Lauria, G., Vanhoutte, E.K., Gerrits, M.M., Dib-Hajj, S., Drenth, J.P.H., Waxman, S.G., and Merkies, I.S.J. Gain-of-function NaV1.7 mutations in idiopathic small fiber neuropathy. Annals of Neurology, 71(1):26-39, 2012. doi:10.1002/ana.22485 PMID: 21698661
Dib-Hajj, S.D., Yang, Y., Black, J.A., Waxman, S.G. The NaV1.7 sodium channel: from molecule to man. Nature Reviews Neuroscience, 14(1): 49-62, 2013. doi:10.1038/nrn3404 PMID: 23232607
Samad, O.A., Tan, A. M., Cheng, X., Foster, E., Dib-Hajj, S.D., Waxman, S.G. Virus-mediated shRNA knockdown of NaV1.3 in rat dorsal root ganglion attenuates nerve-injury induced neuropathic pain. Molecular Therapy, 21(1): 49-56, 2013. doi:10.1038/mt.2012.169 PMID: 22910296
Faber, C.G., Lauria, G., Merkies, I.S.J., Cheng, X., Han, C., Ahn, H-S., Persson, A-K., Hoeijmakers, J.G.J., Gerrits, M.M., Pierro, T., Lombardi, R., Kapetis, D., Dib-Hajj, S.D., and Waxman, S.G. Gain-of-function NaV1.8 mutations in painful neuropathy. Proceedings of the National Academy of Sciences – U.S.A., 109:19444-19449, 2012. doi:10.1073/pnas.1216080109 PMID: 23115331
Yang, Y., Dib-Hajj, S.D., Zhang, J., Zhang, Y., Tyrrell, L., Estacion, M., and Waxman, S.G. Structural modeling and mutant cycle analysis predict pharmacoresponsiveness of a NaV1.7 mutant channel. Nature Communications, 3: 1186, 2012. doi:10.1038/ncomms2184 PMID 23149731
Veeramah, K.R., O’Brien, J.E., Meisler, M.H., Cheng, X., Dib-Hajj, S.D., Waxman, S.G., Talwar, D., Girirajan, S., Eichler, E.E., Restifo, L.L., Erickson, R.P., Hammer, M.F. De novo pathogenic mutation of SCN8A identified by whole genome sequencing of a family quartet with infantile epileptic encephalopathy and SUDEP. American Journal of Human Genetics, 90(3): 502-510, 2012. doi:10.1016/j.ajhg.2012.01.006 PMID: 22365152
Shields, S.D., Butt, R.P., Dib-Hajj, S.D., and Waxman, S.G. Oral administration of PF-01247324, a subtype-selective Nav1.8 blocker, reverses cerebellar deficits in a mouse model of multiple sclerosis. PLoS One, 10(3): e0119067. 2015. doi:10.1371/journal.pone.0119067 PMID: 25747279
Dib-Hajj, S.D., Black, J.A., and Waxman, S.G. NaV1.9: A sodium channel linked to human pain. Nature Reviews – Neuroscience, 16: 511-19, 2015. doi:10.1038/nrn3977 PMID 26243570
Geha, P., Yang, Y., Estacion, M., Schulman, B.R., Tokuno, H., Apkarian, A.V., Dib-Hajj, S.D., Waxman, S.G. Pharmacotherapy for pain in a family with inherited erythromelalgia guided by genomic analysis and functional profiling. JAMA Neurology, 73(6):659-67, 2016. doi:10.1001/jamaneurol.2016.0389 PMID: 27088781
Cao, L., Nitzsche, N., McDonnell, A., Alexandrou, A., Saintot, P-P., Loucif, A.J.C., Brown, A.R., Young, G., Mis, M., Randall, A., Waxman, S.G., Stanley, P., Kirby, S., Tarabar, S., Gutteridge, A., Butt, R., McKernan, R.M., Whiting, R., Ali, Z., Bilsland, J., Stevens, E.B. Pharmacological reversal of pain phenotype in iPSC-derived sensory neurons and human subjects with inherited erythromelalgia. Sci. Transla. Med., 8(335): 335ra56, 2016. doi:10.1126/scitranslmed.aad7653 PMID: 27099175
Zakrzewska, J.M., Palmer, J., Morisset, V., Giblin, G.M.P., Obermann, M., Ettlin, D.A., Cruccu, G., Bendtsen, L., Estacion, M., Derjean, D., Waxman, S.G., Layton, G., Gunn, K., and Tate, S. Safety and efficacy of a NaV1.7-selective sodium channel blocker in trigeminal neuralgia: a double-blind, placebo-controlled, randomized withdrawal phase 2a trial. Lancet Neurology, 16(4):291-300, 2017. doi:10.1016/S1474-4422(17)30005-4 PMID: 28216232
Huang, J., Vanoye, C.G., Cutts, C., Goldberg, Y.P., Dib-Hajj, S.D., Cohen, C.J., Waxman, S.G., and George, A.L. Sodium channel NaV1.9 mutations associated with insensitivity to pain dampen neuronal excitability. Journal of Clinical Investigation, 127(7):2805-2814, 2017. doi:10.1172/JCI92373 PMID: 28530638
Akin, E.J., Higerd, G.P., Mis, M.S., Tanaka, B.S., Adi, T., Liu, S., Dib-Hajj, F.B., Waxman, S.G., and Dib-Hajj, S.D. Building sensory axons: delivery and distributions of NaV1.7 channels and effects of inflammatory mediators. Sci. Adv., 5(10):eaax4755. doi:10.1126/sciadv.aax4755 PMID: 31681845
Vrselja, Z., Daniele, S.G., Silbereis, J., Talpo, F., Morozov, Y.M., Sousa, A.M.M., Tanaka, B.S., Skarica, M., Pletikos, M., Kaur, N., Zhuang, Z.W., Liu, Z., Alkawadri, R., Sinusas, A.J., Latham, S., Waxman, S.G., and Sestan, N. Restoration of brain circulation and cellular functions hours postmortem. Nature, 568(7752):336-343, 2019. doi:10.1038/s41586-019-1099-1 PMID: 30996318
Mis., M., Yang, Y., Tanaka, B., Gomis-Perez, C., Liu, S., Dib-Hajj, F., Adi, T., Garcia-Milian, R., Schulman, B., Dib-Hajj, S., and Waxman, S. Resilience to pain: A peripheral component identified using induced pluripotent stem cells and dynamic clamp. Journal of Neuroscience, 39(3):382-392, 2019. doi:10.1523/JNEUROSCI.2433-18.2018 PMID: 30459225
Gualdani, R., Gailly, P., Yuan, J-H., Yerna, X., DiStefano, G., Truini, A., Cruccu,G., Dib-Hajj, S., and Waxman, S.G. A TRPM7 mutation linked to familial trigeminal neuralgia: omega current and hyperexcitablity of trigeminal ganglion neurons. Proceedings of the National Academy of Sciences – U.S.A., 119(38):e2119630119, 2022. doi:10.1073/pnas.2119630119 PMID: 36095216
Higerd-Rusli, G.P., Tyagi, S., Baker, C.A., Liu, S., Dib-Hajj, F.B., Dib-Hajj, S.D., and Waxman, S.G. Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity. Proceedings of the National Academy of Sciences – U.S.A., 120(11):e2215417120, 2023. doi:10.1073/pnas.2215417120 PMID: 36897973
Waxman, S.G. Targeting a Peripheral Sodium Channel to Treat Pain. New England Journal of Medicine, 389(5):466-469, 2023. doi:10.1056/NEJMe2305708 PMID: 37530829
References
- ^ a b "Stephen George Waxman, MD, PhD > Neurology | Yale School of Medicine". medicine.yale.edu. Retrieved 2018-03-22.
- ^ )
- ^ "Home > Center for Neuroscience and Regeneration Research | Yale School of Medicine". medicine.yale.edu. Retrieved 2018-03-22.
- ^ "About | Neurosciences PhD Program | Stanford Medicine". med.stanford.edu. Retrieved 2018-03-22.
- ^ "Stephen Waxman, MD, PhD | Yale and the World". world.yale.edu. Retrieved 2018-03-22.
- ^ url=https://journals.sagepub.com/editorial-board/NRO
- ^ url=https://medicine.yale.edu/profile/stephen_waxman/
- ISBN 978-0-12-366818-9, retrieved 2023-11-07
- PMID 5013596.
- ISSN 0028-0836.
- ISSN 0028-4793.
- PMID 7965028.
- ISSN 1471-003X.
- ISSN 1471-003X.
- ISSN 0028-3878.
- ISSN 1460-2156.
- ISSN 0364-5134.
- ISSN 0364-5134.
- PMID 23115331.
- ISSN 2168-6149.
- ISSN 2168-6149.
- PMID 30459225.
- ISSN 0028-4793.
- ISSN 0028-4793.
- ^ url=https://medicine.yale.edu/profile/stephen_waxman/