Research Summary

My career in science has been spent in pursuit of molecules which can have profound and disease- modifying impacts on human health. This goal requires knowledge of chemical synthesis, PK/ADME, screening technologies, and emerging biophysical disciplines that are redefining molecule design. As the suite of tools available for characterization of the interaction of small molecules within a biological matrix has expanded, so to has the need to be able to evaluate complex - and sometimes conflicting - data. I have a particular interest in the application of physics-based computation to assess selectivity in ligand binding and the application of AI to accelerate computationally expensive DFT calculation.
Prior to joining UCSF, I led the fragment-based discovery effort at Élan Pharmaceuticals, focused on inhibiting Beta-secretase. While at Élan, I was involved with medicinal chemistry efforts targeting Parkinson’s (alpha-synuclein, LRRK, PLK), Alzheimer’s (gamma-secretase and JNK3), and chronic neuropathic pain (BK1).

Education

Ph.D., 09/2003 - Organic Chemistry, University of Michigan
B.Sc., 05/1994 - Chemistry / Music, Georgetown University

Selected Publications

  1. 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. Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MPro inhibitors with potent in vivo efficacy. Sci Adv. 2025 Apr 25; 11(17):eadt7836.  View on PubMed
  2. Suryawanshi RK, Jaishankar P, Correy GJ, Rachman MM, O'Leary PC, Taha TY, Zapatero-Belinchón FJ, McCavittMalvido M, Doruk YU, Stevens MGV, Diolaiti ME, Jogalekar MP, Richards AL, 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. 2024 Aug 29.  View on PubMed
  3. Ortiz G, Longbotham JE, Qin SL, Zhang MY, Lee GM, Neitz RJ, Kelly MJS, Arkin MR, Fujimori DG. Identifying ligands for the PHD1 finger of KDM5A through high-throughput screening. RSC Chem Biol. 2024 Mar 06; 5(3):209-215.  View on PubMed
  4. Konstantinidou M, Visser EJ, Vandenboorn E, Chen S, Jaishankar P, Overmans M, Dutta S, Neitz RJ, Renslo AR, Ottmann C, Brunsveld L, Arkin MR. Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments. J Am Chem Soc. 2023 09 20; 145(37):20328-20343.  View on PubMed
  5. 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 through Fragment Linking. Angew Chem Int Ed Engl. 2023 09 11; 62(37):e202308004.  View on PubMed
  6. Kenanova DN, Visser EJ, Virta JM, Sijbesma E, Centorrino F, Vickery HR, Zhong M, Neitz RJ, Brunsveld L, Ottmann C, Arkin MR. A Systematic Approach to the Discovery of Protein-Protein Interaction Stabilizers. ACS Cent Sci. 2023 May 24; 9(5):937-946.  View on PubMed
  7. 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
  8. 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
  9. Wolfe AR, Neitz RJ, Burlingame M, Suzuki BM, Lim KC, Scheideler M, Nelson DL, Benet LZ, Caffrey CR TPT sulfonate, a single, oral dose schistosomicidal prodrug: In vivo efficacy, disposition and metabolic profiling.  View on PubMed
  10. LaPorte MG, Burnett JC, Colombo R, Bulfer SL, Alverez C, Chou TF, Neitz RJ, Green N, Moore WJ, Yue Z, Li S, Arkin MR, Wipf P, Huryn DM. Optimization of Phenyl Indole Inhibitors of the AAA+ ATPase p97. ACS Med Chem Lett. 2018 Nov 08; 9(11):1075-1081.  View on PubMed
  11. Banerjee S, Bartesaghi A, Merk A, Rao P, Bulfer SL, Yan Y, Green N, Mroczkowski B, Neitz RJ, Wipf P, Falconieri V, Deshaies RJ, Milne JL, Huryn D, Arkin M, Subramaniam S. 2.3 Å resolution cryo-EM structure of human p97 and mechanism of allosteric inhibition. Science. 2016 Feb 19; 351(6275):871-5.  View on PubMed
  12. Long T, Neitz RJ, Beasley R, Kalyanaraman C, Suzuki BM, Jacobson MP, Dissous C, McKerrow JH, Drewry DH, Zuercher WJ, Singh R, Caffrey CR Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1), a Potential Drug Target in Schistosoma mansoni.  View on PubMed
  13. Alverez C, Bulfer SL, Chakrasali R, Chimenti MS, Deshaies RJ, Green N, Kelly M, LaPorte MG, Lewis TS, Liang M, Moore WJ, Neitz RJ, Peshkov VA, Walters MA, Zhang F, Arkin MR, Wipf P, Huryn DM. Allosteric Indole Amide Inhibitors of p97: Identification of a Novel Probe of the Ubiquitin Pathway. ACS Med Chem Lett. 2016 Feb 11; 7(2):182-7.  View on PubMed
  14. Alverez C, Arkin MR, Bulfer SL, Colombo R, Kovaliov M, LaPorte MG, Lim C, Liang M, Moore WJ, Neitz RJ, Yan Y, Yue Z, Huryn DM, Wipf P. Structure-Activity Study of Bioisosteric Trifluoromethyl and Pentafluorosulfanyl Indole Inhibitors of the AAA ATPase p97. ACS Med Chem Lett. 2015 Dec 10; 6(12):1225-30.  View on PubMed
  15. Khare S, Roach SL, Barnes SW, Hoepfner D, Walker JR, Chatterjee AK, Neitz RJ, Arkin MR, McNamara CW, Ballard J, Lai Y, Fu Y, Molteni V, Yeh V, McKerrow JH, Glynne RJ, Supek F. Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease. PLoS Pathog. 2015 Jul; 11(7):e1005058.  View on PubMed
  16. Neitz RJ, Bryant C, Chen S, Gut J, Hugo Caselli E, Ponce S, Chowdhury S, Xu H, Arkin MR, Ellman JA, Renslo AR. Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas' disease. Bioorg Med Chem Lett. 2015 Nov 01; 25(21):4834-4837.  View on PubMed
  17. Chimenti MS, Bulfer SL, Neitz RJ, Renslo AR, Jacobson MP, James TL, Arkin MR, Kelly MJ. A Fragment-Based Ligand Screen Against Part of a Large Protein Machine: The ND1 Domains of the AAA+ ATPase p97/VCP. J Biomol Screen. 2015 Jul; 20(6):788-800.  View on PubMed
  18. Neitz RJ, Chen S, Supek F, Yeh V, Kellar D, Gut J, Bryant C, Gallardo-Godoy A, Molteni V, Roach SL, Khare S, Stinson M, Chatterjee AK, Robertson S, Renslo AR, Arkin M, Glynne R, McKerrow J, Siqueira-Neto JL. Lead identification to clinical candidate selection: drugs for Chagas disease. J Biomol Screen. 2015 Jan; 20(1):101-11.  View on PubMed
  19. Aubele DL, Hom RK, Adler M, Galemmo RA, Bowers S, Truong AP, Pan H, Beroza P, Neitz RJ, Yao N, Lin M, Tonn G, Zhang H, Bova MP, Ren Z, Tam D, Ruslim L, Baker J, Diep L, Fitzgerald K, Hoffman J, Motter R, Fauss D, Tanaka P, Dappen M, Jagodzinski J, Chan W, Konradi AW, Latimer L, Zhu YL, Sham HL, Anderson JP, Bergeron M, Artis DR Selective and brain-permeable polo-like kinase-2 (Plk-2) inhibitors that reduce α-synuclein phosphorylation in rat brain.  View on PubMed
  20. Ng RA, Sun M, Bowers S, Hom RK, Probst GD, John V, Fang LY, Maillard M, Gailunas A, Brogley L, Neitz RJ, Tung JS, Pleiss MA, Konradi AW, Sham HL, Dappen MS, Adler M, Yao N, Zmolek W, Nakamura D, Quinn KP, Sauer JM, Bova MP, Ruslim L, Artis DR, Yednock TA Design and synthesis of hydroxyethylamine (HEA) BACE-1 inhibitors: prime side chromane-containing inhibitors.  View on PubMed

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