Dr. Steele is a cellular and molecular neurobiologist and Assistant Professor in the Department of Biological Sciences at Humboldt State University. He teaches in the Principles of Biology and CellBiology undergraduate courses, and graduate seminars in his area of research.He received his Bachelor of Arts in Psychology from Kenyon College and Ph.D. inNeuroscience from the Icahn School of Medicine at Mount Sinai in New York City.Dr. Steele completed his postdoctoral training in Neurobiology at RockefellerUniversity with Dr. Paul Greengard (2000 Nobel Laureate), MolecularPharmacology at Amicus Therapeutics, and Stem Cell Biology at UC San Diego withDr. Larry Goldstein. In 2014, he co-founded the company OrPhi Therapeutics,which focuses on the development of therapies for rare neurological diseases. Heis an expert in the fields of molecular neurodegeneration, drug discovery, stem cell biology and genome engineering. His research at HSU focuses on the development of cell-based platforms for drug discovery in the rare neurological disease space, using a combination of human induced stem cells and CRISPR/Cas9 genome editing technologies. His research resulted in patents for drugs to treat Niemann-Pick Disease Type C1 and breakthroughs in understanding of the early molecular pathogenesis of Alzheimer’s disease. 

PEER-REVIEWED PUBLICATIONS

1.    Knight EM, Moreno CL, Hatami A, Albay R, Suzuki A, Beeri MS, Sano M,Purohit DP, Fam P, Maroukian M, Lublin A, Alberini CM, Katsel P, Ehrlich ME,Glabe CG, Haroutunian V, Gandy SE, SteeleJW. Effective anti-Alzheimer’s Ab therapy involves depletion of specific Ab oligomer subtypes. Neurol Neuroimmunol Neuroinflamm 2016 May10; 3(3):e237. PMID: 27218118; PMCID: PMC4864617

2.    Brautigam H, Moreno CL, SteeleJW, Bogush A, Dickstein DL, Kwok JB, Schofield PR, Thinakaran G, MathewsPM, Hof PR, Gandy SE, Ehrlich ME. Physiologically generated presenilin-1lacking exon 8 fails to rescue brain PS1-/-phenotype and forms complexes with wildtype PS1 and nicastrin. Sci Rep 2015 Nov26; 5:17042. PMID: 26608390; PMCID: PMC4660297

3.    Knight EM, Williams HN,Stevens AC, Kim SH, Kottwitz JC, Morant AD, Steele JW, Klein WL, Yanagisawa K, Boyd RE, Lockhart DJ, SjobergER, Ehrlich ME, Wustman BA, Gandy S. Evidence that small molecule enhancementof b-hexosaminidaseactivity corrects the behavioral phenotype in Dutch APP^E693Q micethrough reduction of ganglioside-bound Ab. Mol Psychiatry 2015 Feb; 20(1): 109-17. PMID: 25349165

4.    Kim SH*, Steele JW*,Ehrlich MW, Lee S, Clemenson G, Gage F, Carter T, Treuner K, Gadient R, WedelP, Barlow C, Glabe C, Gandy S. Proneurogenic group II mGluR antagonist improveslearning and reduces anxiety in Alzheimer Ab oligomer mouse. Mol Psychiatry 2014 Nov; 19(11):1235-42. PMID: 25113378; PMCID: PMC4217144 *Co-FirstAuthor

5.    Wang J, Land D, Ono K, Galvez J, Zhao W, Vempati P, Steele JW, Cheng A, Yamada M, Levine S,Mazzola P, Pasinetti GM. Molecular topology as a novel strategy for discoveryof drugs with Ablowering and anti-aggregation dual activities for Alzheimer’s disease. PLoS ONE2014 Mar 26; 9(3): e92750. PMID: 24671215; PMCID: PMC3966818.

6.    Steele JW, BrautigamH, Short JA, Sowa A, Shi M, Yadav A, Weaver CM, Westaway D, Fraser PE, StGeorge-Hyslop PH, Gandy S, Hof PR, Dickstein DL. Early fear memory defects areassociated with altered synaptic plasticity and molecular architecture in theTgCRND8 Alzheimer’s disease mouse model. J Comp Neurol 2014 Jul; 522(10):2319-35. PMID: 24415002; PMCID: PMC4251468.

7.    Sproul AA,Jacob S, Pre D, Kim SH, Nestor MW, Navarro-Sobrino M, Santa-Maria I, Zimmer M,Aubry A, Steele JW, Kahler DJ,Dranovsky A, Arancio O, Crary JF, Gandy S, Noggle SA. Characterization andmolecular profiling of PSEN1 familial Alzheimer’s disease iPSC-derived neuralprogenitors. PLoS ONE 2014 Jan 8; 9(1): e84547. PMID: 24416243;PMCID: PMC3885572.

8.    Lane RF, Steele JW, Ehrlich ME, Attie AD, GandyS. Protein sorting motifs in the cytoplasmic tail of SorCS1 control generationof Alzheimer’s amyloid-beta. J Neurosci 2013 Apr 17; 33(16): 7099-7107, PMID:23595767, PMCID: PMC3696125

9.    De GasperiR, Gama-Sosa MA, Kim SH, Steele JW,Shaughness MC, Maudlin-Jeronimo E, Hall AA, DeKosky ST, McCarron RM, NambiarMP, Gandy S, Ahlers ST, Elder GA. Acute blast injury reduces brain amyloid-betain two rodent species. Front Neurol. 2012; 3:177. PMID: 23267342, PMCID:PMC3527696

10.  Brautigam H, SteeleJW, Westaway D, Fraser P, St George-Hyslop P, Gandy S, Hof PR, DicksteinDL. The isotropic fractionator provides evidence for differential loss ofhippocampal neurons in two mouse models of Alzheimer’s disease. MolNeurodegener. 2012 Nov 22;7(1):58. PMID: 23173713, PMCID: PMC3551697.

11.  Bharadwaj P, Verdile G, Barr RK, Gupta V, Steele JW, Lachenmayer ML, Yue Z,Ehrlich ME, Petsko G, Ju S, Ringe D, Sankovich SE, Caine JM, Macreadie IG,Gandy S, Martins RN. Latrepirdine (Dimebon™) enhances autophagy and reducesintracellular GFP-Abeta42 levels in yeast. J Alzheimers Dis. 2012;32(4):949-67. PMID: 22903131, PMCID: PMC3529125.

12.  Steele JW, Ju S, Lachenmayer ML, Liken J, Stock A, KimSH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Pharadwaj P, Gupta V, Barr R,Friss A, Dolios G, Wang R, Ringe D, Protter AA, Martins RN, Ehrlich ME, Yue Z,Petsko GA, Gandy S. Latrepirdine stimulates autophagy and reduces accumulationof alpha-synuclein in cells and in mouse brain. Mol Psychiatry. 2013 Aug;18(8):882-8. [Epub Aug 7 2012] PMID: 22869031, PMCID: PMC3523214.

13.  Steele JW, Lachenmayer ML, Ju S, Stock A, Liken J, KimSH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Bharadwaj P, Gupta V, Barr R,Friss A, Dolios G, Wang R, Ringe D, Fraser P, Westaway D, St George-Hyslop PH,Szabo P, Relkin NR, Buxbaum JD, Glabe CG, Protter AA, Martins RN, Ehrlich ME,Petsko GA, Yue Z, Gandy S. Latrepirdine improves cognition and arrestsprogression of neuropathology in an Alzheimer’s mouse model. Mol Psychiatry.2013 Aug; 18(8):889-97. [Epub Jul 31 2012] PMID: 22850627, PMCID: PMC3625697.

14.  McFarlane HG, SteeleJW, Vinion K, Bongiovanni R, Double M, Jaskiw GE. Acute lithiumadministration selectively lowers tyrosine levels in serum and brain. BrainResearch 2011 1420: 29-36. PMID: 21962398, PMCID: pending.

15.  Lane RF, Raines SM, Steele JW, Ehrlich ME, Lah JA, Small SA, Tanzi RE, Attie AD, GandyS. Diabetes-associated SorCS1 regulates Alzheimer’s amyloid-beta metabolism:evidence for involvement of SorL1 and the retromer complex. J. Neurosci. 30,13110-13115 (2010). PMID: 20881129; PMCID: PMC3274732.

16.  Gandy S, Simon AJ*, Steele JW*, Lublin AL*, Lah JJ, Walker LC, Levey AI, Krafft GA,Levy E, Checler F, Glabe C, Bilker WB, Abel T, Schmeidler J, Ehrlich ME. Daysto criterion as an indicator of toxicity associated with human alzheimeramyloid-beta oligomers. Ann Neurol. 2010 Aug; 68(2): 220-230. PMID: 20641005,PMCID: PMC3094694. *Denotes equal contribution.

17.  Steele JW, Kim SH, Cirrito JR, Verges DK, Restivo JL, WestawayD, Fraser P, Hyslop PS, Sano M, Bezprozvanny I, Ehrlich ME, Holtzman DM, GandyS. Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic,elevates extracellular amyloid-beta levels in vitro and in vivo. MolNeurodegener. 2009 Dec 17; 4: 51. PMID: 20017949; PMCID: PMC2806870.

REVIEW ARTICLES AND EDITORIALS

1.    Wustman, B.A, Steele,J.W., Sjoberg, E.R., Stevens, A.C. 2014. Bringing dead proteins back tolife. eLife. 2014; 3:e02189. PMID: 24520167; PMCID: PMC3920479.

2.    BharadwajPR, Bates KA, Porter T, Teimouri E, Perry G, Steele JW, Gandy S, Groth D, Martins RN, Verdile G. Latrepirdine:molecular mechanisms underlying potential therapeutic roles in Alzheimer’s andother neurodegenerative diseases. Transl Psychiatry 2013 Dec 3;3: e332. PMID:24301650; PMCID: PMC4030329.

3.    Steele JWand Gandy S. Latrepirdine improves cognition and arrests progression ofneuropathology in an Alzheimer’s mouse model. Autophagy 2013 April; 9(4): 1-2.PMID: 23380933; PMCID: PMC3627679

4.    Steele JW,Duberstein GK, Yue Z. Dimebon, a promising therapeutic with a problematicclinical history. Neurodegen. Dis. Manage 2013; 3(2): 1-4. PMID: pending; DOI:10.2217/nmt.13.5

5.    Steele JW,Fan E, Kelahmetoglu Y, Tian Y, Bustos V. Modulation of autophagy as atherapeutic target for Alzheimer’s disease. J Postdoc Res 2013 Feb; 1(2):21-34. PMID: pending; DOI:10.14304/surya.jpr.v1n2.3

6.    Steele JWand Gandy SE. Apomorphine and Alzheimer Abeta: roles for regulated -cleavage,autophagy, and antioxidation? Ann Neurol. 2011 Mar; 69(2): 221-225. PMID:21387363, PMCID: PMC3071294.

7.    Klionsky DJ, … , Steele JW,… , Zughaier SM. Guidelines for the use and interpretation of assays formonitoring autophagy, Third Edition. Autophagy 2016 Jan; 12(1): 1-222. PMID:26799652.

8.    Ordoñez MP and Steele JW.Modeling Niemann Pick Type C1 using human embryonic and induced pluripotentstem cells. Brain Res 2016 Mar; [Epub ahead of print]. PMID: 26972536; PMCID:PMC5018240.

BOOK CHAPTERS

1.    Steele JW,Goldstein LSB. Dynein and Kinesin (Version 2.0). Encyclopedia of Life Sciences(eLS). ACCEPTED July 30, 2015.

2. Lane RF, Shineman DW, Steele JW, Lee LH, Fillit HM. Beyond Amyloid: The Future of Therapeutics for Alzheimer’s Disease. Advances in Pharmacology 2012; 64: 213-71. PMID: 22840749