Alexander Gow, PhD

Alexander Gow, PhD

agow@med.wayne.edu; ai7965@wayne.edu

313 577-9404; 313 577-9402 (lab)

313 577-1632 (fax)

Alexander Gow, PhD

Narrative Bio

Dr. Alexander Gow is a tenured Professor in the Department of Neurology at Wayne State University School of Medicine. He is also tenured Professor and Associate Director of the Center for Molecular Medicine and Genetics and tenured Professor in the Carman and Ann Adams Department of Pediatrics in the School of Medicine. He relocated from Mount Sinai School of Medicine in New York to Wayne State University in 2000 as Assistant Professor in the Center for Molecular Medicine and Genetics, Department of Neurology and Carman and Ann Adams Department of Pediatrics. He was promoted and tenured in 2003 and promoted to full Professor in 2010. He also received the Charles H. Gershenson Distinguished Faculty Fellow award in 2010. He has served/serves on study sections at the National Institutes of Health (NIDCD and NHLBI), the National Multiple Sclerosis Society, the Italian Government Board of Experts and the US-Israel Binational Science Foundation. At Wayne State School o Medicine, he served for 8 years in the Executive committee of the Faculty Senate.

Dr Gow has an active research laboratory funded by multiple NIH awards from NINDS and NIDCD as well as continuous funded from the National Multiple Sclerosis Society since 1995. He has also received multiple funding awards from local foundations including the William and Marie Carls Foundation, Detroit Medical Center Foundation and the Children’s Foundation of Michigan. He has delivered platform presentations at a number of national and international conferences including the Gordon conference on Myelin in 1992 (discussant), 1994, 1996 and 2008. He described the mechanism of disease for the first misfolded protein disease in 1994 (Pelizaeus Merzbacher disease) and developed a bioassay to predict disease severity in patients in 2006; was first to demonstrate the prosurvival properties of the CHOP transcription factor in the unfolded protein response in 2002; was first to demonstrate the function of the claudin family of tight junction proteins in 1999, and; was first to demonstrate a mechanism by which dysfunctional CNS myelin triggers abnormal behavior and neurotransmitter imbalance in mice as a potential etiology for neuropsychiatric disease in humans in 2018.

Research Summary:
Dr Gow’s research laboratory (http://genetics.wayne.edu/faculty/alexander-gow) is focused on several areas of CNS myelin during development and in disease states and incorporates the auditory pathway as a means of understanding myelin function. The lab takes a multipronged systems approach to studying myelin, including molecular, cell and developmental biology in knockout, knockin and transgenic mice, behavior, confocal and electron microscopy, neurophysiology and evoked potentials, proteomics, genomics and computational modeling. The current projects are divided broadly into:
(1) behavioral studies associated with dysfunctional myelin which is caused by the absence of claudin 11 tight junctions in the compact myelin;
(2) characterization of tight junction-associated proteins in CNS myelin sheaths, and;
(3) generation and characterization of mouse models of the leukodystrophy, Pelizaeus Merzbacher disease, and progressive multiple sclerosis with respect to behavioral, cognitive and memory deficits.

Office Address

3216 Scott Hall, 540 E Canfield, Detroit, MI 48201

Awards & Honors

Research Excellence Award, WSU School of Medicine 2013.
Scientific Advisory Board, Michigan BioTrust, Department of Community Health 2013.
Sustaining Member, Sigma Xi 2011.
Charles H. Gershenson Distinguished Faculty Fellowship 2010–2011.
Marquis Who’s Who 2010.
Research Excellence Award, WSU School of Medicine 2009.
11th percentile score on 1RC1NS068548-01 (PI – Gow) 2009.
School of Medicine Teaching Award, Wayne State University, MI, USA 2008.
Podium presentation, Gordon Conference: Myelin, Il Ciocco, Italy 2008.
Career Development Chair Award, WSU 2006.
Member, National Multiple Sclerosis Society, Study Section B 2006–2011.
Ad Hoc Member: National Institutes of Health, AUD study section 2005–2009.
Member, Sigma Xi 2005.
Treasurer, Executive Committee, Academic Senate, WSU, School of Medicine 2005.
Appointment to Board of Experts, Italian Committee for Research Evaluation (CIVR) 2005.
Research Excellence Award, Wayne State University School of Medicine 2004.
Tenured Associate Professor, Wayne State University 2004.
Scientific Advisory Committee, C.S. Mott Center for Human Growth & Development 2004.
Full Member, Karmanos Cancer Institute, Wayne State University 2003.
9.5th percentile score on 5R01-DC006262 (PI – Gow) 2003.
4th percentile score on 5R01-NS43783 (PI – Gow) 2002.
Podium presentation, Gordon Conference: Myelin, Il Ciocco, Italy 1996.
Podium presentation, Gordon Conference: Myelin, Oxnard, CA, USA 1994.
 

Undergraduate

Biochemistry, NSW Institute of Technology, Sydney, Australia, B.S. December 1979

Graduate

Neurobiology, NSW Institute of Technology, Sydney, Australia M.S. December 1983.
Ph.D. June 1990, Biochemistry, Queensland University, Brisbane, Australia.

Position Title

Professor, Center for Molecular Medicine and Genetics, Pediatrics and Neurology

Specialties

Myelin Biology,Neurodegenerative Disorders and White Matter Diseases

Fellowships

1990 – 1994, Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York.

Prior Appointments

Research Assistant New South Wales I. T., Sydney, Australia, 1980-1983
Research Assistant, Queensland University, Brisbane, Australia, 1983-1990
Assistant Professor, Mount Sinai School of Medicine, NY, 1995-2000

Interests

Protein misfolding diseases of the central and peripheral nervous systems, Pelizaeus-Merzbacher disease, myelinogenesis, demyelination, multiple sclerosis, myelin and saltatory conduction, myelin function and affective disorders, intercellular junctions, tight junctions and auditory function, tight junctions and male infertility, transcriptional regulation of claudin genes.

Publications

 (SELECTED)

1. Maheras KJ*, Peppi M, Ghoddoussi F, Galloway MP, Perrine SA, Gow A (2018) Axon Diameter-Dependent Saltatory Conduction Slowing Perturbs Behavior and Neurotransmitter Levels, Sci Rep, 8, 3798-3813.
2. Maheras KJ*, Pindolia K, Wolf B, Gow A (2017) Developmental Window of Sensorineural Deafness in Biotinidase-Deficient Mice, J Metabol Inherited Dis, doi: 10.1007/s10545-017-0049-z.
3. Southwood CM, Garshott DM, Richardson CR*, Seraji-Bozorgzad N, Fribley AM, Gow A (2017) Dimethyl Fumarate Ameliorates Myoclonus Stemming From Protein Misfolding In Oligodendrocytes, J Neurochem, DOI: 10.1111/jnc.14035.
4. Yellbay B, Gow A, Jamil H (2017) Ranking Novel Regulatory Genes in Gene Expression Profiles using NetExpress, SAC 2017, pp.24-27; doi:10.1145/3019612.3021289.
5. Southwood CM, Fykkolodziej B*, Maheras KJ*, Garshott DM, Estill M*, Fribley AM, Gow A (2016) Overexpression of CHOP in myelinating cells does not confer a significant phenotype under normal or metabolic stress conditions, J Neurosci, 36, 6803-6819.
6. Deninger AR, Breglio A, Maheras KJ*, LeDuc G, Cristiglio V, Deme B, Gow A, Kirschner DA (2015) Claudin-11 tight junctions in myelin are a barrier to diffusion and lack strong adhesive properties, Biophys J, 109, 1387-1397. doi:10.1016/j.bpj.2015.08.012
7. Laukka J, Stanley JA, Garbern JY, Trepanier A, Hobson G, Gow A, Kamholz J (2013) Water diffusion correlates with disease severity in Pelizaeus-Merzbacher disease, J Neurol Sci, 335, 75-81, PMC3969727.
8. Southwood CM, Fykkolodziej B*, Dachet F, Gow A (2013) Potential For Cell-mediated Immune Responses In Mouse Models Of Pelizaeus-Merzbacher Disease, Brain Sci, 3, 1417-1444, NIHMSID: 554476.
9. Maheras KJ*, Gow A (2013) Increased anesthesia time using 2,2,2-tribromoethanol-chloral hydrate with low impact on mouse psychoacoustics J Neurosci Methods, 219, 61-69. PMC3818901.
10. Southwood CM, Lipovich L, Gow A (2012) Tissue-Restricted Transcription from a Conserved Intragenic CpG Island in the Klf1 Gene. Biol Reprod, 87, 108, doi: 10.1095/ biolreprod.112.099879, PMC3509778.
11. Saporta MAC, Shy BR*, Patzko A, Bai Y, Pennuto M, Ferri C, Tinelli E, Saveri P, Kirschner D, Crowther M, Southwood CM, Wu X*, Gow A, Feltri ML, Wrabetz L, Shy ME (2012) MpzR98C arrests Schwann cell development in a mouse model of early-onset Charcot-Marie-Tooth 1B Brain, 135:2032-2047, PMC3381724.
12. Wu X*, Peppi M*, Vengalil MJ*, Maheras KJ*, Southwood CM, Bradley M, Gow A (2012) Transgene-Mediated Rescue of Spermatogenesis in Claudin 11-null Mice. Biol Reprod, 86, 131-139, PMC3364922.
13. Dore-Duffy P, Mehedi A, Wang X, Bradley M, Trotter R, Gow A (2011) Immortalized CNS pericytes are quiescent smooth muscle actin-negative and pluripotent. Microvasc Res, 82, 18-27, PMC3250068.
14. Mazaud-Guittot S, Meugnier E, Pesenti S, Wu X*, Vidal H, Gow A, Le Magueresse-Battistoni B (2010) Claudin11 deficiency results in loss of the Sertoli cell epithelial phenotype in the testis. Biol Reprod, 82, 202-213. PMC2802123.
15. Chen Y, Wu H, Hisami Koito H, Li J, Hoang J, Wang S, Escobar SS, Gow A, Arnett HA, Trapp BD, Karandikar NJ, Hsieh J, Lu QR (2009) The oligodendrocyte-specific G-protein coupled receptor GPR17 is a cell-intrinsic timer of myelination. Nat Neurosci, 12, 1394-1402. PMC2783566.
16. Gow A, Devaux J (2008) Function Of Tight Junctions In CNS Myelinated Axons: Computational Analysis. Neuron Glia Biol, 4, 307-317. PMC2957896.
17. Gould RM, Oakley T, Goldstone JV, Dugas JC, Brady ST, Gow A (2008) Vertebrate myelin sheaths are formed with proteins that most likely originated in vertebrate lineages. Neuron Glia Biol, 4, 137-152. NIHMSID: 512212.
18. Devaux J, Gow A (2008) Tight Junctions Potentiate The Insulative Properties Of Small CNS Myelinated Axons. J Cell Biol, 183, 909-921. PMC2592840.
Feature review, Sedwick, C, J Cell Biol, 183, 752.
19. Sharma R*, Jiang H*, Zhong L*, Tseng J*, Gow A (2007) Minimal Role For Activating Transcription Factor 3 In The Oligodendrocyte Unfolded Protein Response in vivo. J Neurochem, 102, 1703-1712.
20. Sharma R*, Gow A (2007) Minimal role for caspase-12 in the unfolded protein response in oligodendrocytes in vivo. J Neurochem 101, 889-897.
21. Southwood CM, Olson K, Wu C-Y*, Gow A (2007) Novel alternatively-spliced ER retention signal in the cytoplasmic loop of proteolipid protein 1. J Neurosci Res, 85, 471-478.
22. Southwood CM, Peppi M*, Dryden S, Tainsky MA, Gow A (2007) Microtubule deacetylases, SirT2 and HDAC6, in the nervous system. Neurochem Res, 32, 187-195.
23. Nunes FD, Lopez LN, Lin HW, Davies C, Azevedo RB, Gow A, Kachar B (2006) Distinct sub-domain organization and molecular composition of a tight junction with cell-cell adhesion properties. J Cell Sci, 119, 4819-4827.
24. Hurst S, Garbern J, Trepanier A, Gow A (2006) Quantifying the carrier female phenotype in Pelizaeus-Merzbacher disease. Genet Med, 8, 371-378.
25. Xin M, Wu F-F, Ma Z, Gow A, Lu QR (2005) Myelinogenesis and axonal recognition by oligodendrocytes in brain are uncoupled in Olig1-null mice. J Neurosci, 25, 1354-1365.
26. Southwood CM, He C*, Garbern J, Kamholz J, Arroyo E, Gow A (2004) CNS Myelin Paranodes Require Nkx6-2 Homeoprotein Transcriptional Activity for Normal Structure. J Neurosci, 24, 11215-11225.
27. Gow A, Davies C, Southwood CM, Frolenkov G, Chrustowski M*, Ng L, Yamauchi D, Marcus DC, Kachar B (2004) Deafness in Claudin 11-null mice reveals the critical contribution of basal cell tight junctions to stria vascularis function. J Neurosci, 24(32), 7051-7062.
28. Shy M, Hobson G, Boespflug-Tanguy O, Garbern J, Sperle K, Jain M, Li W, Gow A, Rodriguez D, Bertini E, Mancias P, Krajewski K, Lewis RA, Kamholz J, members of the ENBDD (2003) Schwann cell expression of PLP1 but not DM20 is necessary to prevent neuropathy. Ann Neurol, 53, 354-365.
29. Southwood CM, Garbern J, Jiang W*, Gow A (2002) The unfolded protein response modulates disease severity in Pelizaeus-Merzbacher Disease. Neuron, 36, 585-596.
Feature review, Bradbury J (2003) Lancet Neurology, 2, 5.
Feature review, Forman et al, (2003) Trends Neurosci, 26, 407-410.
30. Stecca B*, Southwood CM, Gragerov A, Kelley KA, Friedrich VL, Gow A (2000) The evolution of lipophilin genes from invertebrates to tetrapods: DM-20 cannot replace proteolipid protein in CNS myelin. J Neurosci, 20, 4002-4010.
31. Gow A, Southwood CM, Li JS, Pariali M, Bronstein JM, Riordan GP, Brodie SE, Danias J, Kachar B, Lazzarini RA (1999) CNS Myelin And Sertoli Cell Tight Junction Strands Are Absent In Osp/Claudin 11-Null Mice. Cell, 99,649-659.
32. Gow A, Southwood CM, Lazzarini RA (1998) Disrupted proteolipid protein trafficking results in oligodendrocyte apoptosis in animal models of Pelizaeus-Merzbacher disease. J Cell Biol, 140, 925-934. PMC2141744.
33. Gow A, Gragerov A, Gard A, Colman DR, Lazzarini RA (1997) Conservation of topology, but not conformation, of the proteolipid proteins of the myelin sheath. J Neurosci, 17, 181-189.
34. Gow A, Lazzarini RA (1996) A cellular mechanism governing the severity of Pelizaeus-Merzbacher disease. Nat Genet, 13, 422-428.
35. Gow A, Friedrich Jr VL, Lazzarini RA (1994) Many naturally occurring mutations of myelin PLP impair its intracellular transport. J Neurosci Res, 37, 574-583.
36. Gow A, Friedrich Jr VL, Lazzarini RA (1992) Myelin basic protein gene contains separate enhancers for oligodendrocyte and Schwann cell expression. J Cell Biol, 119, 605-616.

 

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