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. Admasu TD, Kim K, Rae M, Avelar R, Gonciarz RL, Rebbaa A, Pedro de Magalh?es 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
  2. 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 Jan 14; 249:115110.  View on PubMed
  3. 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 Jan 10; 120(2):e2212931120.  View on PubMed
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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 �-lactamase. FEBS Lett. 2021 12; 595(24):2981-2994.  View on PubMed
  12. 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
  13. 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
  14. 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
  15. Gonciarz RL, Collisson EA, Renslo AR. Ferrous Iron-Dependent Pharmacology. Trends Pharmacol Sci. 2021 01; 42(1):7-18.  View on PubMed
  16. Zhao N, Huang Y, Wang YH, Muir RK, Chen YC, Wei J, Hooshdaran N, Viswanath P, Seo Y, Ruggero D, Renslo AR, Evans MJ. Ferronostics: Measuring Tumoral Ferrous Iron with PET to Predict Sensitivity to Iron-Targeted Cancer Therapies. J Nucl Med. 2021 07 01; 62(7):949-955.  View on PubMed
  17. J?lkov? A, Rube?ov? P, Fanfrl?k J, Fajtov? P, Rez?cov? P, Brynda J, Lep??k M, Mertl?kov?-Kaiserov? H, Emal CD, Renslo AR, Roush WR, Horn M, Caffrey CR, Mare? M. Druggable Hot Spots in the Schistosomiasis Cathepsin B1 Target Identified by Functional and Binding Mode Analysis of Potent Vinyl Sulfone Inhibitors. ACS Infect Dis. 2021 05 14; 7(5):1077-1088.  View on PubMed
  18. Chen YC, Oses-Prieto JA, Pope LE, Burlingame AL, Dixon SJ, Renslo AR. Reactivity-Based Probe of the Iron(II)-Dependent Interactome Identifies New Cellular Modulators of Ferroptosis. J Am Chem Soc. 2020 11 11; 142(45):19085-19093.  View on PubMed
  19. Blank BR, Gonciarz RL, Talukder P, Gut J, Legac J, Rosenthal PJ, Renslo AR. Antimalarial Trioxolanes with Superior Drug-Like Properties and In Vivo Efficacy. ACS Infect Dis. 2020 07 10; 6(7):1827-1835.  View on PubMed
  20. Bashore C, Jaishankar P, Skelton NJ, Fuhrmann J, Hearn BR, Liu PS, Renslo AR, Dueber EC. Cyanopyrrolidine Inhibitors of Ubiquitin Specific Protease 7 Mediate Desulfhydration of the Active-Site Cysteine. ACS Chem Biol. 2020 06 19; 15(6):1392-1400.  View on PubMed

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