Larry A. Sklar, Ph.D.

photo of Larry Sklar

The Maralyn S. Budke and Robert E. Anderson Distinguished Endowed Chair in Cancer Drug Discovery

Director, UNM Center for Molecular Discovery

Email: LSklar@salud.unm.edu
Lab Website: Larry A. Sklar: Research


Interests:

  • Signal transduction, cell adhesion, leukocyte biology
  • High throughput technologies for molecular assembly and drug discovery. Targets include GPCRs, Integrins, Efflux Transporters, GTPases
  • Precision Medicine in Cancer
  • Drug Repurposing in Cancer, Infectious disease and Inflammation, Neurodegenerative Diseases, Cardiovascular and Metabolic Diseases
  • Combinatorial libraries for discovery

Big questions:

  • How can we exploit canonical and non-canonical ligand binding sites for cell adhesion, signaling, and transporter molecules as targets for drug discovery?
  • How do we move these discoveries into clinical trials and precision medicine?

Methodology:

  • Real-time analysis of molecular interactions
  • High throughput screening

Education and Certification Information

Helen Hay Whitney Postdoctoral Fellow
Department of Medicine
The Methodist Hospital
Houston, TX
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Helen Hay Whitney Postdoctoral Fellow
Division of Natural Sciences
University of California at Santa Cruz
Santa Cruz, CA
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Ph.D. in Chemistry
Stanford University
Palo Alto, CA
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B.S. in Chemistry
University of Chicago
Chicago, IL
1966-l970


Selected Publications:

  • Jerec W. Ricci, Debbie Lovato, Virginia Severns, Larry A. Sklar, Richard S. Larson. Novel ABCG2 antagonists reverse topotecan-mediated chemotherapeutic resistance in ovarian carcinoma xenografts. Cancer Research Molecular Cancer Therapeutics

  • D. Whitt, Adam B. Keeton, Bernard D. Gary, Larry Sklar, Zhe-Sheng Chen and Gary A. Piazza. Sulindac Sulfide Selectively Increases Sensitivity of ABCC1 Expressing Tumor Cells to Doxorubicin and Glutathione Depletion

  • David B. Sykes 1,2, Youmna S. Kfoury 1, François E. Mercier 1, Mathias J. Wawer 3, Jason M. Law 3, Esha Jain 1, Mark K. Haynes 4, Timothy A. Lewis 3, Amir Schajnovitz 10, Dongjun Lee 1, Hanna Meyer 5, Kerry A. Pierce 6, Nicola J. Tolliday 3, Anna Waller 4, Steven Ferrara 3, Detlef Stoeckigt 5, Katrina L. Maxcy 1, Julien M. Cobert 1, Jacqueline Bachand 1, Brian A. Szekely 1, Siddhartha Mukherjee 7, Larry A. Sklar 4, Joanne D. Kotz 3, Clary B. Clish 6, Ruslan I. Sadrayev 1,8, Paul A. Clemons 3, Andreas Janzer 5, Stuart L. Schreiber 3, David T. Scadden 1,2,9,10. Inhibition of dihydroorotate dehydrogenase overcomes differentiation blockade in acute myeloid leukemia (in press CCR)

  • Yang JJ, Ursu O, Lipinski CA, Sklar LA, Oprea TI, Bologa CG. Badapple: promiscuity patterns from noisy evidence. J Cheminform. 2016 May 28;8:29. doi: 10.1186/s13321-016-0137-3. eCollection 2016. PubMed PMID: 27239230; PubMed Central PMCID: PMC4884375.

  • Perez DR, Smagley Y, Garcia M, Carter MB, Evangelisti A, Matlawska-Wasowska K, Winter SS, Sklar LA, Chigaev A. Cyclic AMP efflux inhibitors as potentialtherapeutic agents for leukemia. Oncotarget. 2016 Apr 25. doi: 10.18632/oncotarget.8986. [Epub ahead of print] PubMed PMID: 27129155.

  • Oprea TI, Sklar LA, Agola JO, Guo Y, Silberberg M, Roxby J, Vestling A, Romero E, Surviladze Z, Murray-Krezan C, Waller A, Ursu O, Hudson LG, Wandinger-Ness A. Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases. PLoS One. 2015 Nov 11;10(11):e0142182. doi: 10.1371/journal.pone.0142182. eCollection 2015. PubMed PMID: 26558612; PubMed Central PMCID: PMC4641600.

  • Chauhan S, Ahmed Z, Bradfute SB, Arko-Mensah J, Mandell MA, Won Choi S, Kimura T, Blanchet F, Waller A, Mudd MH, Jiang S, Sklar L, Timmins GS, Maphis N, Bhaskar K, Piguet V, Deretic V. Pharmaceutical screen identifies novel target processes for activation of autophagy with a broad translational potential. Nat Commun. 2015 Oct 27;6:8620. doi: 10.1038/ncomms9620. PubMed PMID: 26503418; PubMed Central PMCID: PMC4624223.

  • Wu Y, Stauffer SR, Stanfield RL, Tapia PH, Ursu O, Fisher GW, Szent-Gyorgyi C, Evangelisti A, Waller A, Strouse JJ, Carter MB, Bologa C, Gouveia K, Poslusney M, Waggoner AS, Lindsley CW, Jarvik JW, Sklar LA. Discovery of Small-Molecule Nonfluorescent Inhibitors of Fluorogen-Fluorogen Activating Protein Binding Pair. J Biomol Screen. 2015 Oct 6. pii: 1087057115609145. [Epub ahead of print] PubMed. PMID: 26442911.

  • Zhao Z, Haynes MK, Ursu O, Edwards BS, Sklar LA, Zweifach A. A high-throughput phenotypic screen of cytotoxic T lymphocyte lytic granule exocytosis reveals candidate immunosuppressants. J Biomol Screen. 2015 Mar;20(3):359-71. doi: 10.1177/1087057114557620. Epub 2014 Nov 7. PubMed PMID: 25381253; PubMed Central PMCID: PMC4523125.

  • Pinilla C, Edwards BS, Appel JR, Yates-Gibbins T, Giulianotti MA, Medina-Franco JL, Young SM, Santos RG, Sklar LA, Houghten RA. Selective agonists and antagonists of formylpeptide receptors: duplex flow cytometry and mixture-based positional scanning libraries. Mol Pharmacol. 2013 Sep;84(3):314-24. doi: 10.1124/mol.113.086595. Epub 2013 Jun 20. PubMed PMID: 23788657.

  • Santos RG, Appel JR, Giulianotti MA, Edwards BS, Sklar LA, Houghten RA, Pinilla C. The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors. Molecules. 2013 May 30;18(6):6408-24. doi: 10.3390/molecules18066408. PubMed PMID: 23722730.

  • Medina-Franco JL, Edwards BS, Pinilla C, Appel JR, Giulianotti MA, Santos RG, Yongye AB, Sklar LA, Houghten RA. Rapid scanning structure-activity relationships in combinatorial data sets: identification of activity switches. J Chem Inf Model. 2013 Jun 24;53(6):1475-85. doi: 10.1021/ci400192y. Epub 2013 Jun 7. PubMed PMID: 23705689; PubMed Central PMCID: PMC3715655.

  • Strouse JJ, Ivnitski-Steele I, Waller A, Young SM, Perez D, Evangelisti AM, Ursu O, Bologa CG, Carter MB, Salas VM, Tegos G, Larson RS, Oprea TI, Edwards BS, Sklar LA. Fluorescent substrates for flow cytometric evaluation of efflux inhibition in ABCB1, ABCC1, and ABCG2 transporters. Anal Biochem. 2013 Jun 1;437(1):77-87. doi: 10.1016/j.ab.2013.02.018. Epub 2013 Mar 5. PubMed PMID: 23470221; PubMed Central PMCID: PMC3785545.

  • Hong L, Kenney SR, Phillips GK, Simpson D, Schroeder CE, Nöth J, Romero E, Swanson S, Waller A, Strouse JJ, Carter M, Chigaev A, Ursu O, Oprea T, Hjelle B, Golden JE, Aubé J, Hudson LG, Buranda T, Sklar LA, Wandinger-Ness A. Characterization of a Cdc42 protein inhibitor and its use as a molecular probe. J Biol Chem. 2013 Mar 22;288(12):8531-43. doi:10.1074/jbc.M112.435941. Epub 2013 Feb 4. PubMed PMID: 23382385; PubMed Central PMCID: PMC3605667.

  • Wu Y, Tapia PH, Fisher GW, Waggoner AS, Jarvik J, Sklar LA. High-throughput flow cytometry compatible biosensor based on fluorogen activating protein technology. Cytometry A. 2013 Feb;83(2):220-6. doi: 10.1002/cyto.a.22242. Epub 2013 Jan 9. PubMed PMID: 23303704; PubMed Central PMCID: PMC3621705.

  • Florian AE, Lepensky CK, Kwon O, Haynes MK, Sklar LA, Zweifach A. Flow cytometry enables a high-throughput homogeneous fluorescent antibody-binding assay for cytotoxic T cell lytic granule exocytosis. J Biomol Screen. 2013 Apr;18(4):420-9. doi: 10.1177/1087057112466697. Epub 2012 Nov 15. PubMed PMID: 23160568.

  • Williamson EA, Damiani L, Leitao A, Hu C, Hathaway H, Oprea T, Sklar L, Shaheen M, Bauman J, Wang W, Nickoloff JA, Lee SH, Hromas R. Targeting the transposase domain of the DNA repair component Metnase to enhance chemotherapy. Cancer Res. 2012 Dec 1;72(23):6200-8. doi: 10.1158/0008-5472.CAN-12-0313. Epub 2012 Oct 22. PubMed PMID: 23090115.

  • Strouse JJ, Ivnitski-Steele I, Khawaja HM, Perez D, Ricci J, Yao T, Weiner WS, Schroeder CE, Simpson DS, Maki BE, Li K, Golden JE, Foutz TD, Waller A, Evangelisti AM, Young SM, Chavez SE, Garcia MJ, Ursu O, Bologa CG, Carter MB, Salas VM, Gouveia K, Tegos GP, Oprea TI, Edwards BS, Aubé J, Larson RS, Sklar LA. A selective ATP-binding cassette subfamily G member 2 efflux inhibitor revealed via high-throughput flow cytometry. J Biomol Screen. 2013 Jan;18(1):26-38. doi:10.1177/1087057112456875. Epub 2012 Aug 24. PubMed PMID: 22923785; PubMed Central PMCID: PMC3623016.

  • Thal DM, Homan KT, Chen J, Wu EK, Hinkle PM, Huang ZM, Chuprun JK, Song J, Gao E, Cheung JY, Sklar LA, Koch WJ, Tesmer JJ. Paroxetine is a direct inhibitor of g protein-coupled receptor kinase 2 and increases myocardial contractility. ACS Chem Biol. 2012 Nov 16;7(11):1830-9. doi: 10.1021/cb3003013. Epub 2012 Aug 21. PubMed PMID: 22882301; PubMed Central PMCID: PMC3500392.

  • Chigaev A, Sklar LA. Aspects of VLA-4 and LFA-1 regulation that may contribute to rolling and firm adhesion. Front Immunol. 2012;3:242. doi: 10.3389/fimmu.2012.00242. PubMed PMID: 22876249; PubMed Central PMCID: PMC3410440.

  • Polireddy K, Khan MM, Chavan H, Young S, Ma X, Waller A, Garcia M, Perez D, Chavez S, Strouse JJ, Haynes MK, Bologa CG, Oprea TI, Tegos GP, Sklar LA, Krishnamurthy P. A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6. PLoS One. 2012;7(7):e40005. doi: 10.1371/journal.pone.0040005. Epub 2012 Jul 10. PubMed PMID: 22808084; PubMed Central PMCID: PMC3393737.

  • Wu Y, Tapia PH, Fisher GW, Simons PC, Strouse JJ, Foutz T, Waggoner AS, Jarvik J, Sklar LA. Discovery of regulators of receptor internalization with high-throughput flow cytometry. Mol Pharmacol. 2012 Oct;82(4):645-57. Epub 2012 Jul 5. PubMed PMID: 22767611; PubMed Central PMCID: PMC3463215.

  • Agola JO, Hong L, Surviladze Z, Ursu O, Waller A, Strouse JJ, Simpson DS, Schroeder CE, Oprea TI, Golden JE, Aubé J, Buranda T, Sklar LA, Wandinger-Ness A. A competitive nucleotide binding inhibitor: in vitro characterization of Rab7 GTPase inhibition. ACS Chem Biol. 2012 Jun 15;7(6):1095-108. doi: 10.1021/cb3001099. Epub 2012 Apr 23. PubMed PMID: 22486388; PubMed Central PMCID: PMC3440014.

  • Edwards BS, Zhu J, Chen J, Carter MB, Thal DM, Tesmer JJ, Graves SW, Sklar LA. Cluster cytometry for high-capacity bioanalysis. Cytometry A. 2012 May;81(5):419-29. doi: 10.1002/cyto.a.22039. Epub 2012 Mar 21. PubMed PMID: 22438314; PubMed Central PMCID: PMC3331957.

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