Michelle Arkin, PhD

Professor
P_Pharmaceutical Chemistry
+1 415 514-4313

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 co-Director of the Small Molecule Discovery Center, a collaborative research and core lab that includes a high-throughput screening facility and medicinal chemistry (smdc.ucsf.edu).

Publications

Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine.

Proceedings of the National Academy of Sciences of the United States of America

Maciag AE, Yang Y, Sharma AK, Turner DM, DeHart CJ, Abdelkarim H, Fan L, Smith BP, Kumari V, Dyba M, Rigby M, Castillo Badillo JA, Adams L, Fornelli L, Fox S, Brafman A, Turbyville T, Gillette W, Messing S, Agamasu C, Wolfe AL, Gysin S, Chan AH, Simanshu DK, Esposito D, Chertov O, Stephen AG, Arkin M, Renslo A, Kelleher NL, Gaponenko V, Lightstone FC, Nissley DV, McCormick F

Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy.

Science advances

Detomasi TC, Degotte G, Huang S, Suryawanshi RK, Diallo A, Lizzadro L, Zaptero-Belinchón FJ, Taha TY, Li J, Richards AL, Hantz ER, Alam Z, Montano M, McCavitt-Malvido M, Gumpena R, Partridge JR, Correy GJ, Matsui Y, Charvat AF, Glenn IS, Rosecrans J, Revalde JL, Anderson D, Hultquist JF, Arkin MR, Neitz RJ, Swaney DL, Krogan NJ, Shoichet BK, Verba KA, Ott M, Renslo AR, Craik CS

2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy.

Neurobiology of disease

Peck A, Dadi A, Yavarow Z, Alfano LN, Anderson D, Arkin MR, Chou TF, D'Ambrosio ES, Diaz-Manera J, Dudley JP, Elder AG, Ghoshal N, Hart CE, Hart MM, Huryn DM, Johnson AE, Jones KB, Kimonis V, Kiskinis E, Lee EB, Lloyd TE, Mapstone M, Martin A, Meyer H, Mozaffar T, Onyike CU, Pfeffer G, Pindon A, Raman M, Richard I, Rubinsztein DC, Schiava M, Schütz AK, Shen PS, Southworth DR, Staffaroni AM, Taralio-Gravovac M, Weihl CC, Yao Q, Ye Y, Peck N

Truncated tau accumulates before hyperphosphorylated tau and in relatively distinct neuronal subpopulations in entorhinal cortex and inferior temporal gyrus in Alzheimer’s disease patients.

Alzheimer's & Dementia

Ian Michael Oh, Song Hua Li, Felipe Luiz Pereira, Prabhleen Kaur, Anya Raju, Rushil Jerfy, Claudia Kimie Suemoto, Renata Elaine Paraizo Leite, Vitor Ribeiro Paes, Roberta Diehl Rodriguez, Andrew J. Ambrose, Salvatore Spina, William W. Seeley, Bruce L. Miller, Michelle R. Arkin, Lea T. Grinberg

Fragment-based Differential Targeting of PPI Stabilizer Interfaces.

Journal of medicinal chemistry

Guillory X, Wolter M, Leysen S, Neves JF, Kuusk A, Genet S, Somsen B, Morrow J, Rivers E, van Beek L, Patel J, Goodnow R, Schoenherr H, Fuller N, Cao Q, Doveston RG, Brunsveld L, Arkin MR, Castaldi MP, Boyd H, Landrieu I, Chen H, Ottmann C

Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration.

Nature immunology

Ryu JK, Rafalski VA, Meyer-Franke A, Adams RA, Poda SB, Rios Coronado PE, Pedersen LØ, Menon V, Baeten KM, Sikorski SL, Bedard C, Hanspers K, Bardehle S, Mendiola AS, Davalos D, Machado MR, Chan JP, Plastira I, Petersen MA, Pfaff SJ, Ang KK, Hallenbeck KK, Syme C, Hakozaki H, Ellisman MH, Swanson RA, Zamvil SS, Arkin MR, Zorn SH, Pico AR, Mucke L, Freedman SB, Stavenhagen JB, Nelson RB, Akassoglou K

Assay Guidance Manual: Quantitative Biology and Pharmacology in Preclinical Drug Discovery.

Clinical and translational science

Coussens NP, Sittampalam GS, Guha R, Brimacombe K, Grossman A, Chung TDY, Weidner JR, Riss T, Trask OJ, Auld D, Dahlin JL, Devanaryan V, Foley TL, McGee J, Kahl SD, Kales SC, Arkin M, Baell J, Bejcek B, Gal-Edd N, Glicksman M, Haas JV, Iversen PW, Hoeppner M, Lathrop S, Sayers E, Liu H, Trawick B, McVey J, Lemmon VP, Li Z, McManus O, Minor L, Napper A, Wildey MJ, Pacifici R, Chin WW, Xia M, Xu X, Lal-Nag M, Hall MD, Michael S, Inglese J, Simeonov A, Austin CP

Abstract SY23-03: Development and mechanistic characterization of USP7 deubiquitinase inhibitors.

Cancer research

Ingrid Wertz, Lorna Kategaya, Paola Di Lello, Lionel Rouge, Richard Pastor, Kevin R. Clark, Jason Drummond, Tracy Kleinheinz, Eva Lin, John-Paul Upton, Sumit Prakash, Johanna Heideker, Mark McCleland, Maria Stella Ritorto, Dario R. Alessi, Matthias Trost, Travis W. Bainbridge, Michael C. Kwok, Taylur P. Ma, Zachary Stiffler, Bradley Brasher, Yinyan Tang, Priya Jaishanker, Brian Hearn, Adam R. Renslo, Michelle R. Arkin, Frederick Cohen, Kebing Yu, Frank Peale, Florian Gnad, Matthew T. Chang, Christiaan Klijn, Elizabeth Blackwood, Scott E. Martin, William F. Forrest, James A. Ernst, Chudi Ndubaku, Xiaojing Wang, Maureen H. Beresini, Vickie Tsui, Carsten Schwerdtfeger, Robert A. Blake, Jeremy Murray, Till Maurer

USP7 small-molecule inhibitors interfere with ubiquitin binding.

Nature

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

P2X Receptors for ATP: Molecular Properties and Functional Roles.

Richard J. Evans, Ivano Bertini, Giacomo Parigi, Noel Wyn Davies, Victor J. Morris, Marc Willem van der Kamp, Kuniaki Nagayama, Rumiana Koynova, Boris Tenchov, Marc Willem van der Kamp, Abhinav Nath, Elizabeth Rhoades, Marc Willem van der Kamp, Julie S. Biteen, Ranieri Bizzarri, Kuo-Hsiang Tang, Robert E. Blankenship, Ingo Grotjohann, Petra Fromme, Iain L. McConnell, Gary W. Brudvig, Xiaojing Yang, Jacqueline M. Matthews, Derek Marsh, Alison Rodger, Benyamin Rahmani, Hossein Ghanbari, Spyridon Tzamtzis, Gaetano Burriesci, Alexander M. Seifalian, Matt J. Kipper, Stephen E. Harding, Terry Jones, Vivien Jane Coulson-Thomas, Tarsis F. Gesteira, Yvette May Coulson-Thomas, Helena B. Nader, Eija Lehtomaki, Joel P. Mackay, Simon Bernèche, Shi-Bing Yang, Lily Y. Jan, Sami Yunus, Alain M. Jonas, Boris Lakard, Roland Winter, Roland Winter, Assaf Friedler, Chen Katz, Lee Whitmore, Robert W. Janes, Jonathan Hirst, Jacqueline M. Matthews, Alison Rodger, Mikael Akke, Patrik Lundström, Gianfranco Gilardi, Andrew L. Lee, Jamie L. Kear, Gail E. Fanucci, Marc Willem van der Kamp, David R. Skoff, Martin T. Zanni, Robert H. Callender, R. Brian Dyer, Vijay Pande, Clare-Louise Towse, Valerie Daggett, Marc Willem van der Kamp, Gordon C. K. Roberts, Fuyuhiko Inagaki, Jonathan J. Ellis, Boštjan Kobe, Edda Kloppmann, Peter Hoenigschmid, Burkhard Rost, Ertan Eryilmaz, Dongsheng Liu, David Cowburn, Jon I. Mujika, Xabier Lopez, Anna Tramontano, Michael I. Sadowski, Daniel Barry Roche, Maria Teresa Buenavista, Liam James McGuffin, Michael I. Sadowski, Marina V. Rodnina, Jeffrey W. Peng, Marc R. Wilkins, Kleitos Sokratous, José P. Afonso, Preeti Chugha, Michelle Arkin, Gideon Schreiber, Arthur M. Lesk, Barbara Mulloy, Jeffrey J. Warren, James M. Mayer, Inés García-Rubio, Inés García-Rubio, Kandala V. R. Chary, Atul K. Srivastava, Chad Schwartz, Hui Zhang, Peixuan Guo, Russ Hille