Education:
- 1995 - Postdoctoral Training - Biochemistry - Onyx Pharmaceuticals
- 1993 - Postdoctoral Training - Biochemistry - Cornell University
- 1993 - PhD - Biochemistry and Molecular Biology - Cornell University
- 1984 - BA - Biochemistry - University of Connecticut
Clinical/Research Interests:
Dr. Hart applies cutting-edge technologies to high throughput screening (HTS)/rational design-based drug discovery, as well as target discovery. He has directed gene discovery and drug discovery programs in industry and non-profit and academic settings, including at Onyx Pharmaceuticals, Millenium Pharmaceuticals, the Buck Institute, and UT Health San Antonio. These activities used advanced high-throughput screening technologies to support gene target or drug discovery campaigns across aging- and geroscience-relevant therapeutic areas. Dr. Hart has contributed over 70 publications, cited more than 11,000 times, and through gene and drug discovery activities, he has contributed to 75 funded grants, including two NCI Designated Cancer Center funded applications and two NCATS Clinical and Translational Science Awards (CTSA) renewals.
Dr. Hart is the Director of the Center for Therapeutic Sciences (CTS), an inter-institutional hub for drug and target discovery at OUHSC. Under his direction, CTS enables (a) the mapping of genetic pathways driving human disease through CRISPR Whole-Genome High-Throughput Screening (HTS) and (b) the translation of basic science discoveries into therapeutics through HTS/structure-guided design-based small molecule discovery. These activities use sophisticated, robotically integrated detection and imaging instrumentation in high- and ultra-high throughput formats to screen arrayed whole-genome human and mouse sgRNA CRISPR or small molecule libraries.
Select Publications:
Van Skike CE, Lin AL, Roberts Burbank R, Halloran JJ, Hernandez SF, Cuvillier J, Soto VY, Hussong SA, Jahrling JB, Javors MA, Hart MJ, Fischer KE, Austad SN, Galvan V. mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging. Aging Cell. 2020 Jan;19(1):e13057. doi: 10.1111/acel.13057. Epub 2019 Nov 6. PubMed PMID: 31693798; PubMed Central PMCID: PMC6974719.
De La Chapa JJ, Singha PK, Self KK, Sallaway ML, McHardy SF, Hart MJ, McGuff HS, Valdez MC, Ruiz F 2nd, Polusani SR, Gonzales CB. The novel capsazepine analog, CIDD-99, significantly inhibits oral squamous cell carcinoma in vivo through a TRPV1-independent induction of ER stress, mitochondrial dysfunction, and apoptosis. J Oral Pathol Med. 2019 May;48(5):389-399. doi: 10.1111/jop.12843. Epub 2019 Apr 4. PubMed PMID: 30825343; PubMed Central PMCID: PMC6506371.
De La Chapa J, Valdez M, Ruiz F 3rd, Gonzales K, Mitchell W, McHardy SF, Hart M, Polusani SR, Gonzales CB. Synthesis and SAR of novel capsazepine analogs with significant anti-cancer effects in multiple cancer types. Bioorg Med Chem. 2019 Jan 1;27(1):208-215. doi: 10.1016/j.bmc.2018.11.040. Epub 2018 Nov 29. PubMed PMID: 30528162.
De La Chapa J, Singha PK, Sallaway M, Self K, Nasreldin R, Dasari R, Hart M, Kornienko A, Just J, Smith JA, Bissember AC, Gonzales CB. Novel polygodial analogs P3 and P27: Efficacious therapeutic agents disrupting mitochondrial function in oral squamous cell carcinoma. Int J Oncol. 2018 Dec;53(6):2627-2636. doi: 10.3892/ijo.2018.4585. Epub 2018 Oct 5. PubMed PMID: 30320372; PubMed Central PMCID: PMC6203145.
Yi C, Li G, Ivanov DN, Wang Z, Velasco MX, Hernández G, Kaundal S, Villarreal J, Gupta YK, Qiao M, Hubert CG, Hart MJ, Penalva LOF. Luteolin inhibits Musashi1 binding to RNA and disrupts cancer phenotypes in glioblastoma cells. RNA Biol. 2018;15(11):1420-1432. doi: 10.1080/15476286.2018.1539607. Epub 2018 Nov 18. PubMed PMID: 30362859; PubMed Central PMCID: PMC6284574.
Zhang SY, Clark NE, Freije CA, Pauwels E, Taggart AJ, Okada S, Mandel H, Garcia P, Ciancanelli MJ, Biran A, Lafaille FG, Tsumura M, Cobat A, Luo J, Volpi S, Zimmer B, Sakata S, Dinis A, Ohara O, Garcia Reino EJ, Dobbs K, Hasek M, Holloway SP, McCammon K, Hussong SA, DeRosa N, Van Skike CE, Katolik A, Lorenzo L, Hyodo M, Faria E, Halwani R, Fukuhara R, Smith GA, Galvan V, Damha MJ, Al-Muhsen S, Itan Y, Boeke JD, Notarangelo LD, Studer L, Kobayashi M, Diogo L, Fairbrother WG, Abel L, Rosenberg BR, Hart PJ, Etzioni A, Casanova JL. Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection. Cell. 2018 Feb 22;172(5):952-965.e18. doi: 10.1016/j.cell.2018.02.019. PubMed PMID: 29474921; PubMed Central PMCID: PMC5886375.
Kim SK, Barron L, Hinck CS, Petrunak EM, Cano KE, Thangirala A, Iskra B, Brothers M, Vonberg M, Leal B, Richter B, Kodali R, Taylor AB, Du S, Barnes CO, Sulea T, Calero G, Hart PJ, Hart MJ, Demeler B, Hinck AP. An engineered transforming growth factor β (TGF-β) monomer that functions as a dominant negative to block TGF-β signaling. J Biol Chem. 2017 Apr 28;292(17):7173-7188. doi: 10.1074/jbc.M116.768754. Epub 2017 Feb 22. PubMed PMID: 28228478; PubMed Central PMCID: PMC5409485.
Galvan V, Hart MJ. Vascular mTOR-dependent mechanisms linking the control of aging to Alzheimer's disease. Biochim Biophys Acta. 2016 May;1862(5):992-1007. doi: 10.1016/j.bbadis.2015.11.010. Epub 2015 Nov 27. Review. PubMed PMID: 26639036; PubMed Central PMCID: PMC6762019.
Bai X, Wey MC, Fernandez E, Hart MJ, Gelfond J, Bokov AF, Rani S, Strong R. Rapamycin improves motor function, reduces 4-hydroxynonenal adducted protein in brain, and attenuates synaptic injury in a mouse model of synucleinopathy. Pathobiol Aging Age Relat Dis. 2015;5:28743. doi: 10.3402/pba.v5.28743. eCollection 2015. PubMed PMID: 26306821; PubMed Central PMCID: PMC4549373.
Zhang Q, Descamps O, Hart MJ, Poksay KS, Spilman P, Kane DJ, Gorostiza O, John V, Bredesen DE. Paradoxical effect of TrkA inhibition in Alzheimer's disease models. J Alzheimers Dis. 2014;40(3):605-617. doi: 10.3233/JAD-130017. PubMed PMID: 24531152; PubMed Central PMCID: PMC4091737.
Theendakara V, Patent A, Peters Libeu CA, Philpot B, Flores S, Descamps O, Poksay KS, Zhang Q, Cailing G, Hart M, John V, Rao RV, Bredesen DE. Neuroprotective Sirtuin ratio reversed by ApoE4. Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18303-8. doi: 10.1073/pnas.1314145110. Epub 2013 Oct 21. PubMed PMID: 24145446; PubMed Central PMCID: PMC3831497.
Lin AL, Zheng W, Halloran JJ, Burbank RR, Hussong SA, Hart MJ, Javors M, Shih YY, Muir E, Solano Fonseca R, Strong R, Richardson AG, Lechleiter JD, Fox PT, Galvan V. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease. J Cereb Blood Flow Metab. 2013 Sep;33(9):1412-21. doi: 10.1038/jcbfm.2013.82. Epub 2013 Jun 26. PubMed PMID: 23801246; PubMed Central PMCID: PMC3764385.
Pierce A, Podlutskaya N, Halloran JJ, Hussong SA, Lin PY, Burbank R, Hart MJ, Galvan V. Over-expression of heat shock factor 1 phenocopies the effect of chronic inhibition of TOR by rapamycin and is sufficient to ameliorate Alzheimer's-like deficits in mice modeling the disease. J Neurochem. 2013 Mar;124(6):880-93. doi: 10.1111/jnc.12080. Epub 2012 Dec 26. PubMed PMID: 23121022; PubMed Central PMCID: PMC6762020.
Halloran J, Hussong SA, Burbank R, Podlutskaya N, Fischer KE, Sloane LB, Austad SN, Strong R, Richardson A, Hart MJ, Galvan V. Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience. 2012 Oct 25;223:102-13. doi: 10.1016/j.neuroscience.2012.06.054. Epub 2012 Jun 28. PubMed PMID: 22750207; PubMed Central PMCID: PMC3454865.
Khan MH, Hart MJ, Rea SL. The role of MAP4K3 in lifespan regulation of Caenorhabditis elegans. Biochem Biophys Res Commun. 2012 Aug 24;425(2):413-8. doi: 10.1016/j.bbrc.2012.07.113. Epub 2012 Jul 27. PubMed PMID: 22846570.
Hart MJ, Glicksman M, Liu M, Sharma MK, Cuny G, Galvan V. Development of a high-throughput screen targeting caspase-8-mediated cleavage of the amyloid precursor protein. Anal Biochem. 2012 Feb 15;421(2):467-76. doi: 10.1016/j.ab.2011.11.020. Epub 2011 Dec 1. PubMed PMID: 22178911.
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