University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Michelle Arkin, PhD

Michelle Arkin, PhD

Professor, Department of Pharmaceutical Chemistry, UCSF

Cancer Center Program Memberships

Experimental Therapeutics

Research Summary

Michelle’s lab develops innovative approaches to screen for chemical tools and drug leads, using biophysical approaches like fragment-based drug discovery and biological approaches including high-content imaging with primary cells and organisms. Our goal is to demonstrate ‘druggability’ of new target classes and to use our compounds to discover new targets for drug discovery. Areas of interest include protein-protein interactions, allosteric and scaffolding sites in enzymes, and orphan and neglected diseases. Michelle is Associate Director of the Small Molecule Discovery Center, a collaborative research and core lab that includes a high-throughput screening facility (smdc.ucsf.edu).

Education

1990, Bryn Mawr College, Bryn Mawr, PA, B.A., Chemistry
1997, California Institute of Technology, Pasadena, CA, Ph.D., Chemistry
1999, Genentech, Inc, South San Francisco, CA and Sunesis Pharmaceuticals, Redwood City, CA, Postdoctoral fellowship, Protein Engineering


Professional Experience

  • 1999 - 2007
    Scientist, Staff Scientist, Senior Scientist, Associate Director of Cell Biology, Sunesis Pharmaceuticals, South San Francisco, CA
  • 2007 - present
    Associate Director, Biology, Small Molecule Discovery Center, UCSF
  • 2007 - 2013
    Assistant Adjunct Professor, Pharmaceutical Chemistry, UCSF
  • 2011 - 2013
    Associate Adjunct Professor, Pharmaceutical Chemistry, UCSF
  • 2014 - 2017
    Associate Professor in Residence, Pharmaceutical Chemistry, UCSF
  • 2017 - present
    Professor in Residence, Pharmaceutical Chemistry, UCSF

Honors & Awards

  • 1991
    European Traveling Fellowship, Bryn Mawr College
  • 1991-1992
    Blodgett Fellowship, General Electric Foundation
  • 1992-1995
    National Science Foundation Predoctoral Fellowship
  • 1995-1997
    National Institutes of Health Traineeship
  • 1997-1999
    Daymon Runyon-Walter Winchell Cancer Research Postdoctoral Fellowship
  • 2010
    Keynote address, Drug Discovery Chemistry, Protein-Protein Interactions (San Diego)
  • 2012
    Keynote speaker, EFMC-ISMC (Berlin)
  • 2013
    Keynote speaker, PPI-NET (London)
  • 2013
    Finalist, SLAS Innovation Award

Selected Publications

  1. Kategaya L, Di Lello P, Rougé L, Pastor R, Clark KR, Drummond J, Kleinheinz T, Lin E, Upton JP, Prakash S, Heideker J, McCleland M, Ritorto MS, Alessi DR, Trost M, Bainbridge TW, Kwok MCM, Ma TP, Stiffler Z, Brasher B, Tang Y, Jaishankar P, Hearn BR, Renslo AR, Arkin MR, Cohen F, Yu K, Peale F, Gnad F, Chang MT, Klijn C, Blackwood E, Martin SE, Forrest WF, Ernst JA, Ndubaku C, Wang X, Beresini MH, Tsui V, Schwerdtfeger C, Blake RA, Murray J, Maurer T, Wertz IE. USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature. 2017 Oct 26; 550(7677):534-538.
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  2. Theofilas P, Ehrenberg AJ, Nguy A, Thackrey JM, Dunlop S, Mejia MB, Alho AT, Paraizo Leite RE, Rodriguez RD, Suemoto CK, Nascimento CF, Chin M, Medina-Cleghorn D, Cuervo AM, Arkin M, Seeley WW, Miller BL, Nitrini R, Pasqualucci CA, Filho WJ, Rueb U, Neuhaus J, Heinsen H, Grinberg LT. Probing the correlation of neuronal loss, neurofibrillary tangles, and cell death markers across the Alzheimer's disease Braak stages: a quantitative study in humans. Neurobiol Aging. 2017 Sep 20; 61:1-12.
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  3. Hallenbeck KK, Davies JL, Merron C, Ogden P, Sijbesma E, Ottmann C, Renslo AR, Wilson C, Arkin MR. A Liquid Chromatography/Mass Spectrometry Method for Screening Disulfide Tethering Fragments. SLAS Discov. 2017 Sep 01; 2472555217732072.
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  4. Carlson HK, Mullan MR, Mosqueda LA, Chen S, Arkin MR, Coates JD. High-Throughput Screening To Identify Potent and Specific Inhibitors of Microbial Sulfate Reduction. Environ Sci Technol. 2017 Jun 20; 51(12):7278-7285.
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  5. Burnett JC, Lim C, Peyser BD, Samankumara LP, Kovaliov M, Colombo R, Bulfer SL, LaPorte MG, Hermone AR, McGrath CF, Arkin MR, Gussio R, Huryn DM, Wipf P. A threonine turnstile defines a dynamic amphiphilic binding motif in the AAA ATPase p97 allosteric binding site. Org Biomol Chem. 2017 May 16; 15(19):4096-4114.
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  6. Pappalardo Z, Gambhir Chopra D, Hennings TG, Richards H, Choe J, Yang K, Baeyens L, Ang K, Chen S, Arkin M, German MS, McManus MT, Ku GM. A Whole-Genome RNA Interference Screen Reveals a Role for Spry2 in Insulin Transcription and the Unfolded Protein Response. Diabetes. 2017 Jun; 66(6):1703-1712.
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  7. Hallenbeck KK, Turner DM, Renslo AR, Arkin MR. Targeting Non-Catalytic Cysteine Residues Through Structure-Guided Drug Discovery. Curr Top Med Chem. 2017; 17(1):4-15.
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  8. Visperas PR, Wilson CG, Winger JA, Yan Q, Lin K, Arkin MR, Weiss A, Kuriyan J. Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen. SLAS Discov. 2017 Mar; 22(3):324-331.
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  9. Liu H, Chen S, Huang K, Kim J, Mo H, Iovine R, Gendre J, Pascal P, Li Q, Sun Y, Dong Z, Arkin M, Guo S, Huang B. A High-Content Larval Zebrafish Brain Imaging Method for Small Molecule Drug Discovery. PLoS One. 2016; 11(10):e0164645.
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  10. Gallagher CM, Garri C, Cain EL, Ang KK, Wilson CG, Chen S, Hearn BR, Jaishankar P, Aranda-Diaz A, Arkin MR, Renslo AR, Walter P. Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6a branch. Elife. 2016 Jul 20; 5.
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  11. Bulfer SL, Chou TF, Arkin MR. p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein-Protein Interactions. ACS Chem Biol. 2016 Aug 19; 11(8):2112-6.
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  12. Banerjee S, Bartesaghi A, Merk A, Rao P, Bulfer SL, Yan Y, Green N, Mroczkowski B, Neitz RJ, Wipf P, Falconieri V, Deshaies RJ, Milne JL, Huryn D, Arkin M, Subramaniam S. 2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. Science. 2016 Feb 19; 351(6275):871-5.
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  13. Alverez C, Bulfer SL, Chakrasali R, Chimenti MS, Deshaies RJ, Green N, Kelly M, LaPorte MG, Lewis TS, Liang M, Moore WJ, Neitz RJ, Peshkov VA, Walters MA, Zhang F, Arkin MR, Wipf P, Huryn DM. Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway. ACS Med Chem Lett. 2016 Feb 11; 7(2):182-7.
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  14. Suzawa M, Miranda DA, Ramos KA, Ang KK, Faivre EJ, Wilson CG, Caboni L, Arkin MR, Kim YS, Fletterick RJ, Diaz A, Schneekloth JS, Ingraham HA. A gene-expression screen identifies a non-toxic sumoylation inhibitor that mimics SUMO-less human LRH-1 in liver. Elife. 2015 Dec 11; 4.
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  15. Visscher M, Arkin MR, Dansen TB. Covalent targeting of acquired cysteines in cancer. Curr Opin Chem Biol. 2016 Feb; 30:61-67.
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  16. Alverez C, Arkin MR, Bulfer SL, Colombo R, Kovaliov M, LaPorte MG, Lim C, Liang M, Moore WJ, Neitz RJ, Yan Y, Yue Z, Huryn DM, Wipf P. Structure-Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97. ACS Med Chem Lett. 2015 Dec 10; 6(12):1225-30.
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  17. Frye SV, Arkin MR, Arrowsmith CH, Conn PJ, Glicksman MA, Hull-Ryde EA, Slusher BS. Tackling reproducibility in academic preclinical drug discovery. Nat Rev Drug Discov. 2015 11; 14(11):733-4.
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  18. Khare S, Roach SL, Barnes SW, Hoepfner D, Walker JR, Chatterjee AK, Neitz RJ, Arkin MR, McNamara CW, Ballard J, Lai Y, Fu Y, Molteni V, Yeh V, McKerrow JH, Glynne RJ, Supek F. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease. PLoS Pathog. 2015 Jul; 11(7):e1005058.
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  19. Ekins S, de Siqueira-Neto JL, McCall LI, Sarker M, Yadav M, Ponder EL, Kallel EA, Kellar D, Chen S, Arkin M, Bunin BA, McKerrow JH, Talcott C. Machine Learning Models and Pathway Genome Data Base for Trypanosoma cruzi Drug Discovery. PLoS Negl Trop Dis. 2015; 9(6):e0003878.
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  20. Neitz RJ, Bryant C, Chen S, Gut J, Caselli EH, Ponce S, Chowdhury S, Xu H, Arkin MR, Ellman JA, Renslo AR. Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas' disease. Bioorg Med Chem Lett. 2015 Nov 01; 25(21):4834-7.
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