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

  • April 6, 2021 - March 31, 2026 - Evolution and inhibition of carbapenemase in beta-lactam resistance , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI161762
  • April 1, 2021 - March 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
  • 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
  • May 29, 2013 - August 31, 2023 - Chemical Methods for Ferrous Iron Dependent Drug Delivery , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01AI105106

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. Visser EJ, Jaishankar P, Sijbesma E, Pennings MAM, Vandenboorn EMF, Guillory X, Neitz RJ, Morrow J, Dutta S, Renslo AR, Brunsveld L, Arkin MR, Ottmann C. From tethered to freestanding stabilizers of 14-3-3 protein-protein interactions via fragment linking. Angew Chem Int Ed Engl. 2023 Jul 16; e202308004.  View on PubMed
  2. Togo T, Tram L, Denton LG, ElHilali-Pollard X, Gu J, Jiang J, Liu C, Zhao Y, Zhao Y, Zheng Y, Zheng Y, Yang J, Fan P, Arkin MR, Härmä H, Sun D, Canan SS, Wheeler SE, Renslo AR. Systematic Study of Heteroarene Stacking Using a Congeneric Set of Molecular Glues for Procaspase-6. J Med Chem. 2023 Jul 05.  View on PubMed
  3. Fink EA, Bardine C, Gahbauer S, Singh I, Detomasi TC, White K, Gu S, Wan X, Chen J, Ary B, Glenn I, O'Connell J, O'Donnell H, Fajtová P, Lyu J, Vigneron S, Young NJ, Kondratov IS, Alisoltani A, Simons LM, Lorenzo-Redondo R, Ozer EA, Hultquist JF, O'Donoghue AJ, Moroz YS, Taunton J, Renslo AR, Irwin JJ, García-Sastre A, Shoichet BK, Craik CS. Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors. Protein Sci. 2023 08; 32(8):e4712.  View on PubMed
  4. Van Horn KS, Wang D, Medina-Cleghorn D, Lee PS, Bryant C, Altobelli C, Jaishankar P, Leung KK, Ng RA, Ambrose AJ, Tang Y, Arkin MR, Renslo AR. Engaging a Non-catalytic Cysteine Residue Drives Potent and Selective Inhibition of Caspase-6. J Am Chem Soc. 2023 05 10; 145(18):10015-10021.  View on PubMed
  5. Blank BR, Gut J, Rosenthal PJ, Renslo AR. Artefenomel Regioisomer RLA-3107 Is a Promising Lead for the Discovery of Next-Generation Endoperoxide Antimalarials. ACS Med Chem Lett. 2023 Apr 13; 14(4):493-498.  View on PubMed
  6. Admasu TD, Kim K, Rae M, Avelar R, Gonciarz RL, Rebbaa A, Pedro de Magalhães J, Renslo AR, Stolzing A, Sharma A. Selective ablation of primary and paracrine senescent cells by targeting iron dyshomeostasis. Cell Rep. 2023 Feb 06; 42(2):112058.  View on PubMed
  7. Gonciarz RL, Sakhamuri S, Hooshdaran N, Kumar G, Kim H, Evans MJ, Renslo AR. Elevated labile iron in castration-resistant prostate cancer is targetable with ferrous iron-activatable antiandrogen therapy. Eur J Med Chem. 2023 Mar 05; 249:115110.  View on PubMed
  8. Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko DS, Moroz YS, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS. Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2. Proc Natl Acad Sci U S A. 2023 01 10; 120(2):e2212931120.  View on PubMed
  9. Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko D, Moroz Y, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS. Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2. bioRxiv. 2022 Jul 28.  View on PubMed
  10. Shimizu H, Renslo AR. Systematic Exploration of Passive Permeability in Tetrapeptides with Hydrogen-Bond-Accepting Amino Acid Side Chains. ChemMedChem. 2022 08 17; 17(16):e202200204.  View on PubMed
  11. Sacco MD, Defrees K, Zhang X, Lawless W, Nwanochie E, Balsizer A, Darch SE, Renslo AR, Chen Y. Structure-Based Ligand Design Targeting Pseudomonas aeruginosa LpxA in Lipid A Biosynthesis. ACS Infect Dis. 2022 07 08; 8(7):1231-1240.  View on PubMed
  12. Hulce KR, Jaishankar P, Lee GM, Bohn MF, Connelly EJ, Wucherer K, Ongpipattanakul C, Volk RF, Chuo SW, Arkin MR, Renslo AR, Craik CS. Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine. Cell Chem Biol. 2022 05 19; 29(5):785-798.e19.  View on PubMed
  13. Jiang H, Muir RK, Gonciarz RL, Olshen AB, Yeh I, Hann BC, Zhao N, Wang YH, Behr SC, Korkola JE, Evans MJ, Collisson EA, Renslo AR. Ferrous iron-activatable drug conjugate achieves potent MAPK blockade in KRAS-driven tumors. J Exp Med. 2022 04 04; 219(4).  View on PubMed
  14. Gunderson EL, Bryant C, Bulman CA, Fischer C, Luo M, Vogel I, Lim KC, Jawahar S, Tricoche N, Voronin D, Corbo C, Ayiseh RB, Manfo FPT, Mbah GE, Cho-Ngwa F, Beerntsen B, Renslo AR, Lustigman S, Sakanari JA. Pyrvinium Pamoate and Structural Analogs Are Early Macrofilaricide Leads. Pharmaceuticals (Basel). 2022 Feb 02; 15(2).  View on PubMed
  15. Chen J, Gonciarz RL, Renslo AR. Correction: Expanded scope of Griesbaum co-ozonolysis for the preparation of structurally diverse sensors of ferrous iron. RSC Adv. 2021 Nov 10; 11(58):36625.  View on PubMed
  16. Kemp MT, Nichols DA, Zhang X, Defrees K, Na I, Renslo AR, Chen Y. Mutation of the conserved Asp-Asp pair impairs the structure, function, and inhibition of CTX-M Class A β-lactamase. FEBS Lett. 2021 12; 595(24):2981-2994.  View on PubMed
  17. Chen J, Gonciarz RL, Renslo AR. Expanded scope of Griesbaum co-ozonolysis for the preparation of structurally diverse sensors of ferrous iron. RSC Adv. 2021 Oct 18; 11(54):34338-34342.  View on PubMed
  18. Kim GJ, Mo H, Liu H, Wu Z, Chen S, Zheng J, Zhao X, Nucum D, Shortland J, Peng L, Elepano M, Tang B, Olson S, Paras N, Li H, Renslo AR, Arkin MR, Huang B, Lu B, Sirota M, Guo S. A zebrafish screen reveals Renin-angiotensin system inhibitors as neuroprotective via mitochondrial restoration in dopamine neurons. Elife. 2021 09 22; 10.  View on PubMed
  19. Gonciarz RL, Renslo AR. Emerging role of ferrous iron in bacterial growth and host-pathogen interaction: New tools for chemical (micro)biology and antibacterial therapy. Curr Opin Chem Biol. 2021 04; 61:170-178.  View on PubMed
  20. Gonciarz RL, Collisson EA, Renslo AR. Ferrous Iron-Dependent Pharmacology. Trends Pharmacol Sci. 2021 01; 42(1):7-18.  View on PubMed

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