Research Summary

My research group is engaged at the interface of chemistry and biology. As medicinal chemists, we design and synthesize small molecules that modulate disease pathology at the level of the enzyme, cell, and whole animal, with active projects in cancer, infectious disease, and neurodegeneration. Our group also developed a parallel synthetic methodology to produce a library of disulfide 'fragments', thereby enabling cysteine-disulfide (Tethering) screening at UCSF. Finally, we design, synthesize and validate novel small molecule probes for the study of labile ferrous iron in biology and disease. Most recently, we described the first of a new class of activity-based probes for proximity labelling of proteins in an iron-dependent fashion, thus enabling the first chemoproteomic studies of the labile iron 'interactome'.

Research Funding

  • August 10, 2026 - July 31, 2031 - Development of Broad-Spectrum Inhibitors of Serine and Metallo Carbapenemases of ESKAPE Pathogens , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI201855
  • January 1, 2023 - November 30, 2027 - Development of caspase-6 inhibitors for treatment of NASH , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01DK135289
  • April 1, 2021 - May 31, 2026 - Understanding efficacy and FE(II)-Promoted Activation of 1,2,4-Trioxolanes in cancer , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA260860
  • April 6, 2021 - March 31, 2026 - Evolution and inhibition of carbapenemase in beta-lactam resistance , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI161762
  • July 1, 2021 - March 31, 2025 - Developing a pretargeting strategy to detect Fe(II) for nuclear medicine applications , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01EB029429
  • September 30, 2023 - February 28, 2025 - Optimizing brain penetrance of caspase-6 inhibitors to treat neurodegenerative diseases , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R41AG078036
  • May 29, 2013 - August 31, 2023 - Chemical Methods for Ferrous Iron Dependent Drug Delivery , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI105106
  • February 1, 2019 - January 31, 2021 - Discovery of Novel Antimalarial Leads Targeting Translational Repression in Plasmodium parasites , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI135495
  • March 1, 2018 - January 31, 2021 - Expanding the Chemical Biology of K2P Channels with Selective Cellular and In vivo Probes , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01MH116278
  • December 4, 2017 - November 30, 2019 - Biophysical Fragment Screening and Structure Determination for Class A, B, and D Carbapenemases , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI135489
  • March 1, 2011 - February 28, 2013 - Chemical Methods for Ferrous Iron Targeted Drug Delivery , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21AI094433
  • January 1, 2009 - December 31, 2011 - Identification of Anti-HIV Lead Compounds Targeting Rev , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R41AI076087

Education

St. Olaf College, Northfield, MN, B.A., 05/1993, Chemistry
Massachusetts Institute of Technology, Ph.D., 05/1998, Organic Chemistry
The Scripps Research Institute, La Jolla, CA, Postdoctoral, 12/2000, Molecular Recognition

Selected Publications

  1. Kim J, Correy GJ, Hall BW, Rachman MM, Mailhot O, Togo T, Gonciarz RL, Jaishankar P, Neitz RJ, Hantz ER, Doruk YU, Stevens MGV, Diolaiti ME, Reid R, Gopalkrishnan S, Krogan NJ, Renslo AR, Ashworth A, Shoichet BK, Fraser JS. Large-scale prospective evaluation of co-folding across hundreds of Mac1-ligand complexes and three virtual screens. Elife. 2026 Oct 12; 15. View on PubMed
  2. Biswas I, Wang Q, McCann JT, Tchesnokov EP, Nguyen L, Saini M, Cantero J, Revalde JL, Götte M, Renslo AR, Neitz RJ, Arkin MR, Arnold E, Ruiz FX. Discovery of non-nucleoside inhibitors of the enterovirus D68 3D polymerase through crystallographic fragment and high-throughput biochemical screening. bioRxiv. 2026 Jul 10. View on PubMed
  3. Feng X, Zhang S, Wang Y, Kurlagunda T, Sit A, Jaishankar P, Yang P, Sakane S, Park SY, Wisessaowapak C, Nguyen K, Yan J, Pothulu H, Dinh C, Chu F, Ren Y, Zhang B, Secrest P, Han L, Hung CW, Veeragandham P, Skorobogatko Y, Kisseleva T, Gordts PLSM, Renslo AR, Zhao P, Majithia AR, Saltiel AR. Dietary cholesterol activates a Ral-dependent pathway driving LDLR turnover. Nature. 2026 Aug; 656(8127):452-462. View on PubMed
  4. Inniss NL, Rzhetskaya M, Kich RP, Gleason E, Taha TY, Zapatero-Belinchón FJ, Rosecrans J, Pedrero-Classen V, Huang K, Degotte G, Lizzadro L, Pattie J, Renslo AR, Minasov G, Ott M, Bachta KER, Satchell KJF, Hultquist JF. Repurposing drug screen for the identification of helicase inhibitors from viruses of pandemic concern. SLAS Discov. 2026 08; 41:100311. View on PubMed
  5. Ponnusamy V, Randall DR, Lee ZH, Das NK, Zhao L, Buscher K, Solanki S, Renslo AR, Hsu PP, Shah YM. Labile iron pool dynamics do not drive ferroptosis in colorectal cancer cells. J Biol Chem. 2026 May; 302(5):111357. View on PubMed
  6. Jacobs LMC, Jaishankar P, Zheng J, Hantz ER, Lee I, Narramneni K, Poore N, Torres N, Jackson JK, Williams O, Darch SE, Shaw LN, Chen Y, Renslo AR. Structure-Based Design of Reversible, Quinoline-2(1H)‑one Inhibitors of Serine- and Metallo-Carbapenemases. ACS Omega. 2026 Mar 10; 11(9):15316-15327. View on PubMed
  7. Lizzadro L, Li J, Taha TY, Degotte G, Detomasi TC, Zapatero-Belinchon FJ, Hantz ER, Huang S, Matsui Y, Henderson WR, McCann JT, Montano M, Rosecrans J, Torres Pomares DF, McGovern BL, Diaz-Tapia R, Benjamin J, Gordon ME, Suazo ID, Settineri NS, Diallo A, Krogan NJ, Shoichet BK, Verba KA, Albrecht R, García-Sastre A, White KM, Ott M, Craik CS, Renslo AR. Discovery of Coronavirus Main Protease Inhibitors with Enhanced Brain Exposure and Potent Oral Efficacy in SARS-CoV-2 and MERS Infection Models. J Med Chem. 2026 Jan 22; 69(2):1530-1551. View on PubMed
  8. Kim J, Correy GJ, Hall BW, Rachman MM, Mailhot O, Togo T, Gonciarz RL, Jaishankar P, Neitz RJ, Hantz ER, Doruk YU, Stevens MGV, Diolaiti ME, Reid R, Gopalkrishnan S, Krogan NJ, Renslo AR, Ashworth A, Shoichet BK, Fraser JS. Large scale prospective evaluation of co-folding across 557 Mac1-ligand complexes and three virtual screens. bioRxiv. 2025 Dec 29. View on PubMed
  9. Seo L, Farran I, Aslam A, Li X, Jaishankar P, Ashworth A, Fraser JS, Renslo AR, Wankowicz SA. Crystallographic Ensembles Reveal the Structural Basis of Binding Entropy in SARS-CoV2 Macrodomain. bioRxiv. 2025 Dec 23. View on PubMed
  10. Jaishankar P, Correy GJ, Matsui Y, Togo T, Rachman MM, Stevens MGV, Hantz ER, Zheng J, Diolaiti ME, Montano M, Taha TY, Rosecrans J, Pampel J, Krogan NJ, Shoichet BK, Ashworth A, Ott M, Fraser JS, Renslo AR. Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy In Vivo. J Med Chem. 2026 Jan 08; 69(1):553-573. View on PubMed
  11. Suryawanshi RK, Jaishankar P, Correy GJ, Rachman MM, O'Leary PC, Taha TY, Matsui Y, Zapatero-Belinchón FJ, McCavitt-Malvido M, Doruk YU, Stevens MGV, Diolaiti ME, Jogalekar MP, Chen H, Richards AL, Kongpracha P, Bali S, Montano M, Rosecrans J, Matthay M, Togo T, Gonciarz RL, Gopalkrishnan S, Neitz RJ, Krogan NJ, Swaney DL, Shoichet BK, Ott M, Renslo AR, Ashworth A, Fraser JS. The Mac1 ADP-ribosylhydrolase is a therapeutic target for SARS-CoV-2. Elife. 2025 Nov 19; 14. View on PubMed
  12. Jaishankar P, Correy GJ, Matsui Y, Togo T, Rachman MM, Stevens MGV, Hantz ER, Zheng J, Diolaiti ME, Montano M, Taha TY, Rosecrans J, Pampel J, Krogan NJ, Shoichet BK, Ashworth A, Ott M, Fraser JS, Renslo AR. Discovery of AVI-6451, a Potent and Selective Inhibitor of the SARS-CoV-2 ADP-Ribosylhydrolase Mac1 with Oral Efficacy in vivo. bioRxiv. 2025 Oct 14. View on PubMed
  13. Suryawanshi RK, Jaishankar P, Correy GJ, Rachman MM, O'Leary PC, Taha TY, Matsui Y, Zapatero-Belinchón FJ, McCavitt-Malvido M, Doruk YU, Stevens MGV, Diolaiti ME, Jogalekar MP, Chen H, Richards AL, Kongpracha P, Bali S, Montano M, Rosecrans J, Matthay M, Togo T, Gonciarz RL, Gopalkrishnan S, Neitz RJ, Krogan NJ, Swaney DL, Shoichet BK, Ott M, Renslo AR, Ashworth A, Fraser JS. The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2. bioRxiv. 2025 Oct 06. View on PubMed
  14. Ponnusamy V, Randall DR, Lee ZH, Das NK, Zhao L, Buscher K, Solanki S, Renslo AR, Hsu PP, Shah YM. Labile iron pool dynamics do not drive ferroptosis potentiation in colorectal cancer cells. bioRxiv. 2025 Sep 15. View on PubMed
  15. Klope MT, Talukder P, Blank BR, Chelebieva S, Chen J, Fontaine SD, Gonciarz RL, Jaishankar P, Lee GJ, Legac J, Mathur V, Narayan A, Okitwi M, Orena S, Settineri NS, Tapia JA, Taremwa Y, Tumwebaze PK, Vinod A, Burrows JN, Rosenthal PJ, Cooper RA, Renslo AR. Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance. Sci Adv. 2025 Aug 08; 11(32):eads9168. View on PubMed
  16. Flowers J, Echols N, Correy GJ, Jaishankar P, Togo T, Renslo AR, van den Bedem H, Fraser JS, Wankowicz SA. Expanding automated multiconformer ligand modeling to macrocycles and fragments. Elife. 2025 Jun 30; 14. View on PubMed
  17. Correy GJ, Rachman MM, Togo T, Gahbauer S, Doruk YU, Stevens MGV, Jaishankar P, Kelley B, Goldman B, Schmidt M, Kramer T, Radchenko DS, Moroz YS, Ashworth A, Riley P, Shoichet BK, Renslo AR, Walters WP, Fraser JS. Exploration of structure-activity relationships for the SARS-CoV-2 macrodomain from shape-based fragment linking and active learning. Sci Adv. 2025 May 30; 11(22):eads7187. View on PubMed
  18. 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. Blocking C-terminal processing of KRAS4b via a direct covalent attack on the CaaX-box cysteine. Proc Natl Acad Sci U S A. 2025 May 13; 122(19):e2410766122. View on PubMed
  19. Flowers J, Echols N, Correy G, Jaishankar P, Togo T, Renslo AR, van den Bedem H, Fraser JS, Wankowicz SA. Expanding Automated Multiconformer Ligand Modeling to Macrocycles and Fragments. bioRxiv. 2025 Apr 30. View on PubMed
  20. Detomasi TC, Degotte G, Huang S, Suryawanshi RK, Diallo A, Lizzadro L, Zapatero-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. Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy. Sci Adv. 2025 04 25; 11(17):eadt7836. View on PubMed

Go to UCSF Profiles, powered by CTSI