Edwin Rubel

Rubel completed his undergraduate and graduate education at Michigan State University. He received his MA in Psychology in 1967 for the thesis "Imprinting in the Quail, Coturnix coturnix".{{Cite thesis |last= Rubel |first= Edwin W |date= 1967 |title=Imprinting in the Quail, Coturnix coturnix |type= MA|url=https://doi.org/doi:10.25335/M5P843X3B |publisher=Michigan State University |doi= 10.25335/M5P843X3B |accessdate=October 26, 2021}} He received his PhD in Psychology in 1969 for his thesis entitled "A comparison of somatotopic organization in sensory neocortex of newborn kittens and adult cats",{{Cite thesis |last= Rubel |first= Edwin W |date= 1969 |url=https://doi.org/doi:10.25335/M5KK94M48 |type=PhD |title=A comparison of somatotopic organization in sensory neocortex of newborn kittens and adult cats |publisher=Michigan State University |doi= 10.25335/M5KK94M48 |accessdate=October 26, 2021}} published in the Journal of Comparative Neurology in 1971.{{Cite journal |last=Rubel |first=Edwin W |title=A comparison of somatotopic organization in sensory neocortex of newborn kittens and adult cats. |journal=J Comp Neurol |date=1971 |volume=143 |issue=4 |pages=447–480 |doi=10.1002/cne.901430404|pmid=11393201 |s2cid=15475388 }} His PhD advisors were John I. Johnson.{{cite web | title=John "Jack" Irwin Johnson, Ph.D.| website=MSU Division of Human Anatomy | url=https://anatomy.msu.edu/directory/faculty/view-staff-member/528 | ref={{sfnref | Division of Human Anatomy}} | access-date=2021-10-27}} and Glen I. Hatton.

Rubel's research is on methods and preparations to better understand the development, plasticity, pathology and potential repair of the inner ear and auditory pathways of the brain,{{Cite web |url=http://depts.washington.edu/rubelab/ |title=Rubel Lab |publisher=washington.edu |accessdate=May 13, 2017}} and has published over 300 papers.{{PubMedAuthorSearch|Rubel|EW}} He has made contributions to several different areas of auditory neuroscience.{{cite book |doi= 10.1007/978-3-319-21530-3_1 |chapter= Auditory System Development: A Tribute to Edwin W Rubel |title= Auditory Development and Plasticity |series= Springer Handbook of Auditory Research |year= 2017 |last1= Cramer |first1= Karina S. |last2= Coffin |first2= Allison B. |volume= 64 |pages= 1–15 |isbn= 978-3-319-21529-7 }} These include studies of the development and plasticity of neurons in the auditory brainstem, damage and regeneration of hair cells and protection of the mechanosensory cells in the inner ear for hearing and balance.

Auditory brainstem

Rubel and colleagues made considerable contributions to the study of the auditory brainstem, describing the anatomy, organization, development and plasticity of these structures in birds and mammals. Studies included descriptions of the tonotopic organization of brainstem nuclei in chick,{{cite journal |vauthors=Rubel EW, Parks TN |title=Organization and development of brain stem auditory nuclei of the chicken: tonotopic organization of n. magnocellularis and n. laminaris |journal=J Comp Neurol |date=1975 |volume=164 |issue=4 |pages=411–33 |doi=10.1002/cne.901640403 |pmid= 1206127 |s2cid=605374 }}{{cite journal |vauthors=Parks TN, Rubel EW |title=Organization and development of brain stem auditory nuclei of the chicken: organization of projections from n. magnocellularis to n. laminaris |journal=J Comp Neurol |date=1975 |volume=164 |issue=4 |pages=435–48 |doi=10.1002/cne.901640404 |pmid=1206128|s2cid=14288196 }} leading to identification of neural circuitry underlying interaural time differences.{{cite journal |vauthors=Young SR, Rubel EW |title=Frequency-specific projections of individual neurons in chick brainstem auditory nuclei |journal=J Neurosci |date=1983 |volume=3 |issue=7 |pages=1373–8 |doi=10.1523/JNEUROSCI.03-07-01373.1983 |pmid=6864252 |pmc=6564442 }}{{cite journal |vauthors=Overholt EM, Rubel EW, Hyson RL |title=A circuit for coding interaural time differences in the chick brainstem |journal=J Neurosci |date=1992 |volume=12 |issue=5 |pages=1698–708 |doi=10.1523/JNEUROSCI.12-05-01698.1992 |pmid=1578264 |pmc=6575867 }} His group also studied the effects of cochlear removal on brainstem organization in chick {{cite journal |vauthors=Born DE, Rubel EW |title=Afferent influences on brain stem auditory nuclei of the chicken: neuron number and size following cochlea removal |journal=J Comp Neurol |date=1985 |volume=231 |issue=4 |pages=435–45 |doi=10.1002/cne.902310403 |pmid=3968247|s2cid=8087908 |citeseerx=10.1.1.421.1525 }} and in gerbil,{{cite journal |vauthors=Hashisaki GT, Rubel EW |title=Effects of unilateral cochlea removal on anteroventral cochlear nucleus neurons in developing gerbils |journal=J Comp Neurol |date=1989 |volume=283 |issue=4 |pages=5–73 |doi=10.1002/cne.902830402 |pmid=2745749|s2cid=24876401 }} demonstrating a critical period for cochlear influences.

Hair cell regeneration

Rubel and colleagues demonstrated that hair cell regeneration occurred in birds after exposure to aminoglycoside antibiotics{{ cite journal |vauthors=Cruz RM, Lambert PR, Rubel EW |title=Light microscopic evidence of hair cell regeneration after gentamicin toxicity in chick cochlea |journal=Arch Otolaryngol Head Neck Surg |date=1987 |volume=113 |issue=10 |pages=1058–62 |doi=10.1001/archotol.1987.01860100036017 |pmid=3620125}} or acoustic trauma,{{cite journal |vauthors=Ryals BM, Rubel EW |title=Hair cell regeneration after acoustic trauma in adult Coturnix quail|journal=Science |date=1988 |volume=240 |issue=4860 |pages=1774–6 |doi=10.1126/science.3381101 |pmid=3381101|bibcode=1988Sci...240.1774R}} paralleling studies by Cotanche{{cite journal |vauthors=Cotanche DA |title=Regeneration of hair cell stereociliary bundles in the chick cochlea following severe acoustic trauma |journal=Hear Res |date=1987 |volume=30 |issue=2–3 |pages=181–95 |doi=10.1016/0378-5955(87)90135-3 |pmid=3680064 |s2cid=4700764 }} and Corwin and Cotanche.{{cite journal |vauthors=Corwin JT, Cotanche DA |title=Regeneration of sensory hair cells after acoustic trauma |journal=Science |date=1988 |volume=240 |issue=4860 |pages=1772–4 |doi=10.1126/science.3381100 |pmid=3381100 |bibcode=1988Sci...240.1772C }} Prior to these studies it was generally believed that hair cell regeneration did not occur in warm-blooded animals.{{cite journal |vauthors=Rubel EW, Furrer SA, Stone JS |title=A brief history of hair cell regeneration research and speculations on the future |journal=Hear Res |date=2013 |volume=297 |pages=42–51 |doi=10.1016/j.heares.2012.12.014 |pmid=23321648 |pmc=3657556}}

Hair cell damage and prevention of hearing loss

With colleagues at the University of Washington and Fred Hutchinson Cancer Research Center, Rubel develop the zebrafish as a model system for understanding hair cell damage and regeneration.{{Cite news |url=https://www.wsj.com/articles/SB10001424052970204563304574320823841860910 |title=Can a Tiny Fish Save Your Ears? |newspaper=Wall Street Journal |date=5 August 2009 |publisher=wsj.com |accessdate=October 22, 2021|last1=Wang |first1=Shirley S. }}{{cite journal |vauthors=Harris JA, Cheng AG, Cunningham LL, MacDonald G, Raible DW, Rubel EW |title=Neomycin-induced hair cell death and rapid regeneration in the lateral line of zebrafish (Danio rerio) |journal=J Assoc Res Otolaryngol |date=2003 |volume=4 |issue=2 |pages=219–34 |doi=10.1007/s10162-002-3022-x |pmid=12943374 |pmc=3202713}} Studies identified mutations that altered susceptibility to ototoxic agents, and small molecule screens for compounds that prevent hair cell damage.{{cite journal |vauthors=Owens KN, Santos F, Roberts B, Linbo T, Coffin AB, Knisely AJ, Simon JA, Rubel EW, Raible DW |title=Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death |journal=PLOS Genet |date=2008 |volume=4 |issue=2 |pages=e1000020 |doi=10.1371/journal.pgen.1000020 |pmid=18454195 |pmc=2265478 |doi-access=free }} Through iterative chemistry, they developed a lead compound with improved otoprotective potency, improved pharmacokinetic properties and reduced off-target activity (ORC-13661).{{cite journal |vauthors=Chowdhury S, Owens KN, Herr RJ, Jiang Q, Chen X, Johnson G, Groppi VE, Raible DW, Rubel EW, Simon JA |title=Phenotypic Optimization of Urea-Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss |journal=J Med Chem |date=2018 |volume=61 |issue=1 |pages=84–97 |doi=10.1021/acs.jmedchem.7b00932 |pmid=28992413 |pmc=5889090}} This compound has been licensed to Oricula Therapeutics, co-founded by Rubel, and has been approved for use in humans by the FDA.{{cite web | title=Oricula Therapeutics Gets FDA Clearance for Clinical Trials with Investigational New Drug | website=Hearing News Watch | date=2018-02-07 | url=https://hearinghealthmatters.org/hearingnewswatch/2018/oricula-hearing-loss-drug-trial-orc-13661/ | ref={{sfnref | Hearing News Watch | 2018}} | access-date=2021-10-27}}

Rubel served on the advisory council of the National Institute on Deafness and Communication Disorders from 1991 to 1995. He became a Fellow of the American Association for the Advancement of Science in 1999. Rubel served as president of the Association for Research in Otolaryngology (ARO) in 1999, and was awarded the Award of Merit from the ARO in 2005.{{Cite web |url=http://depts.washington.edu/mednews/vol8/no46/rubel.html |title=Edwin Rubel wins otolaryngology association's highest award |publisher=washington.edu |accessdate=October 22, 2021}} He has served on the editorial boards of a number of journals including Hearing Research, Journal of Neuroscience and the Journal of Comparative Neurology.

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Category:University of Washington faculty

Category:American otolaryngologists

Category:Michigan State University alumni

Category:Living people

Category:1942 births