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 current projects in cancer, infectious disease, and neurodegeneration. As chemical biologists, we employ novel small molecule probes to better understand biological pathways and the mechanisms of small molecule therapeutics. Using such small molecule probes, we are exploring the mechanisms underlying the action of artemisinin and related antimalarial drugs. Finally, we are inventing and employing new platform technologies in an effort to expand the realm of druggable target space and drug-like chemical space. These technologies include fragment-based approaches to target protein-protein interfaces and allosteric modulation of enzymes, the use of novel unnatural amino acids to discover cell-permeable peptides, and new targeted prodrug approaches in cancer and infectious disease.

Research Funding

  • May 29, 2013 - August 31, 2023 - Chemical Methods for Ferrous Iron Dependent Drug Delivery, Principal Investigator. Sponsor: NIH/NIAID, 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/NIAID, 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/NIMH, 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/NIAID, Sponsor Award ID: R21AI135489

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. 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
  2. Gonciarz RL, Collisson EA, Renslo AR. Ferrous Iron-Dependent Pharmacology. Trends Pharmacol Sci. 2021 01; 42(1):7-18.  View on PubMed
  3. 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 Jul 01; 62(7):949-955.  View on PubMed
  4. Jílková A, Rubešová P, Fanfrlík J, Fajtová P, Rezácová P, Brynda J, Lepšík M, Mertlíková-Kaiserová H, Emal CD, Renslo AR, Roush WR, Horn M, Caffrey CR, Mareš 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
  5. 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
  6. 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
  7. 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
  8. Huff TC, Camarena V, Sant DW, Wilkes Z, Van Booven D, Aron AT, Muir RK, Renslo AR, Chang CJ, Monje PV, Wang G. Oscillatory cAMP signaling rapidly alters H3K4 methylation. Life Sci Alliance. 2020 01; 3(1).  View on PubMed
  9. Pemberton OA, Jaishankar P, Akhtar A, Adams JL, Shaw LN, Renslo AR, Chen Y. Heteroaryl Phosphonates as Noncovalent Inhibitors of Both Serine- and Metallocarbapenemases. J Med Chem. 2019 09 26; 62(18):8480-8496.  View on PubMed
  10. Griffin AL, Jaishankar P, Grandjean JM, Olson SH, Renslo AR, Baraban SC. Zebrafish studies identify serotonin receptors mediating antiepileptic activity in Dravet syndrome. Brain Commun. 2019; 1(1):fcz008.  View on PubMed
  11. Ehrnhoefer DE, Skotte NH, Reinshagen J, Qiu X, Windshügel B, Jaishankar P, Ladha S, Petina O, Khankischpur M, Nguyen YTN, Caron NS, Razeto A, Meyer Zu Rheda M, Deng Y, Huynh KT, Wittig I, Gribbon P, Renslo AR, Geffken D, Gul S, Hayden MR. Activation of Caspase-6 Is Promoted by a Mutant Huntingtin Fragment and Blocked by an Allosteric Inhibitor Compound. Cell Chem Biol. 2019 09 19; 26(9):1295-1305.e6.  View on PubMed
  12. Blank BR, Talukder P, Muir RK, Green ER, Skaar EP, Renslo AR. Targeting Mobilization of Ferrous Iron in Pseudomonas aeruginosa Infection with an Iron(II)-Caged LpxC Inhibitor. ACS Infect Dis. 2019 08 09; 5(8):1366-1375.  View on PubMed
  13. DeFrees K, Kemp MT, ElHilali-Pollard X, Zhang X, Mohamed A, Chen Y, Renslo AR. An Empirical Study of Amide-Heteroarene p-Stacking Interactions Using Reversible Inhibitors of a Bacterial Serine Hydrolase. Org Chem Front. 2019 Jun 07; 6(11):1749-1756.  View on PubMed
  14. Torelli NJ, Akhtar A, DeFrees K, Jaishankar P, Pemberton OA, Zhang X, Johnson C, Renslo AR, Chen Y. Active-Site Druggability of Carbapenemases and Broad-Spectrum Inhibitor Discovery. ACS Infect Dis. 2019 06 14; 5(6):1013-1021.  View on PubMed
  15. Muir RK, Zhao N, Wei J, Wang YH, Moroz A, Huang Y, Chen YC, Sriram R, Kurhanewicz J, Ruggero D, Renslo AR, Evans MJ. Measuring Dynamic Changes in the Labile Iron Pool in Vivo with a Reactivity-Based Probe for Positron Emission Tomography. ACS Cent Sci. 2019 Apr 24; 5(4):727-736.  View on PubMed
  16. Raleigh DR, Sever N, Choksi PK, Sigg MA, Hines KM, Thompson BM, Elnatan D, Jaishankar P, Bisignano P, Garcia-Gonzalo FR, Krup AL, Eberl M, Byrne EFX, Siebold C, Wong SY, Renslo AR, Grabe M, McDonald JG, Xu L, Beachy PA, Reiter JF. Cilia-Associated Oxysterols Activate Smoothened. Mol Cell. 2018 10 18; 72(2):316-327.e5.  View on PubMed
  17. Pope L, Arrigoni C, Lou H, Bryant C, Gallardo-Godoy A, Renslo AR, Minor DL. Protein and Chemical Determinants of BL-1249 Action and Selectivity for K2P Channels. ACS Chem Neurosci. 2018 12 19; 9(12):3153-3165.  View on PubMed
  18. Pemberton OA, Zhang X, Nichols DA, DeFrees K, Jaishankar P, Bonnet R, Adams J, Shaw LN, Renslo AR, Chen Y. Antibacterial Spectrum of a Tetrazole-Based Reversible Inhibitor of Serine ß-Lactamases. Antimicrob Agents Chemother. 2018 08; 62(8).  View on PubMed
  19. Tsai JC, Miller-Vedam LE, Anand AA, Jaishankar P, Nguyen HC, Renslo AR, Frost A, Walter P. Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule. Science. 2018 03 30; 359(6383).  View on PubMed
  20. Spangler B, Kline T, Hanson J, Li X, Zhou S, Wells JA, Sato AK, Renslo AR. Toward a Ferrous Iron-Cleavable Linker for Antibody-Drug Conjugates. Mol Pharm. 2018 05 07; 15(5):2054-2059.  View on PubMed

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