Daniel K. Nomura is an American chemical biologist and Professor of Chemical Biology and Molecular Therapeutics at the University of California, Berkeley, in the Departments of Chemistry and Molecular & Cell Biology. His work employs chemoproteomic approaches to develop small molecule therapeutics and therapeutic modalities against traditionally "undruggable" proteins.[1]

Daniel K. Nomura
BornJuly 10th, 1981
Alma materUniversity of California, Berkeley; University of California, Berkeley
Scientific career
FieldsChemical Biology, Chemistry, Molecular and Cell Biology, Drug Discovery, Cancer Biology
Institutions
  • UC Berkeley
  • Innovative Genomics Institute
  • Novartis-Berkeley Translational Chemical Biology Institute

He is a member of the scientific advisory committee of the Mark Foundation for Cancer Research, a foundation set up by billionaire Alexander Knaster which funds early-stage cancer research. [2] He is also an Investment Advisory Partner for a16z, an Investment Advisor for Droia Ventures, and an iPartner with The Column Group.[3]

Research and education

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Nomura received his BA in Molecular and Cell Biology in 2003 and PhD in Molecular Toxicology in 2008 from UC Berkeley, studying under the mentorship of John Casida. He went on to perform his postdoctoral research with Ben Cravatt at Scripps Research in La Jolla, California. There he discovered a role for monoacylglycerol lipase in generating oncogenic signaling lipids that promote cancer[4] and in proinflammatory cascades that impact neurodegenerative disorders.[5] In 2011, Nomura started his independent research group at UC Berkeley. His work focuses on implementing chemoproteomic platforms to develop small molecule therapeutics against traditionally "undruggable" proteins. These approaches have led to the discovery of novel inhibitors and new ligands that expand the scope of proteolysis targeting chimeras (PROTACS),[6] which are bifunctional molecules that harness the cells ubiquitin-proteasome system to degrade targets of interest. Notable recent discoveries include an inhibitor of mTORC1,[7] a molecular glue between UBR7 and p53 that activates p53 tumor suppressor activity,[8] a covalent inhibitor against MYC,[9] novel covalent recruiters against E3 ubiquitin ligases such as RNF114, RNF4, and FEM1B for targeted protein degradation applications,[10][11][12] the Deubiquitinase Targeting Chimera (DUBTAC) platform for targeted protein stabilization,[13] and a chemical rational design strategy for developing molecular glue degraders.[14] In 2017, Nomura became the Director of the Novartis-Berkeley Translational Chemical Biology Institute,[15][16] which aims to develop chemical technologies and therapeutics against undruggable targets. Nomura is also co-founder of Frontier Medicines and Vicinitas Therapeutics.[17][18]

Awards

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  • 2019 Mark Foundation for Cancer Research ASPIRE award [19] [20]
  • 2022 National Cancer Institute Outstanding Investigator Award [21]

References

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  1. ^ "Novartis and Berkeley researchers team up to tackle the industry's toughest drug targets". Chemical & Engineering News. Retrieved 2020-08-27.
  2. ^ "Daniel Nomura, PhD". 26 January 2021.
  3. ^ "Droia Ventures – Investing in Impact – Life Science". Droia Ventures – Investing in Impact. Retrieved 2022-11-21.
  4. ^ Nomura, Daniel K.; Long, Jonathan Z.; Niessen, Sherry; Hoover, Heather S.; Ng, Shu-Wing; Cravatt, Benjamin F. (2010-01-08). "Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis". Cell. 140 (1): 49–61. doi:10.1016/j.cell.2009.11.027. ISSN 1097-4172. PMC 2885975. PMID 20079333.
  5. ^ Nomura, Daniel K.; Morrison, Bradley E.; Blankman, Jacqueline L.; Long, Jonathan Z.; Kinsey, Steven G.; Marcondes, Maria Cecilia G.; Ward, Anna M.; Hahn, Yun Kyung; Lichtman, Aron H.; Conti, Bruno; Cravatt, Benjamin F. (2011-11-11). "Endocannabinoid hydrolysis generates brain prostaglandins that promote neuroinflammation". Science. 334 (6057): 809–813. Bibcode:2011Sci...334..809N. doi:10.1126/science.1209200. ISSN 1095-9203. PMC 3249428. PMID 22021672.
  6. ^ Jarvis, Lisa M. "Targeted protein degraders are redefining how small molecules look and act". Chemical & Engineering News. Retrieved 2020-08-27.
  7. ^ Chung, Clive Yik-Sham; Shin, Hijai R.; Berdan, Charles A.; Ford, Breanna; Ward, Carl C.; Olzmann, James A.; Zoncu, Roberto; Nomura, Daniel K. (August 2019). "Covalent targeting of the vacuolar H -ATPase activates autophagy via mTORC1 inhibition". Nature Chemical Biology. 15 (8): 776–785. doi:10.1038/s41589-019-0308-4. ISSN 1552-4469. PMC 6641988. PMID 31285595.
  8. ^ Isobe, Yosuke; Okumura, Mikiko; McGregor, Lynn M.; Brittain, Scott M.; Jones, Michael D.; Liang, Xiaoyou; White, Ross; Forrester, William; McKenna, Jeffrey M.; Tallarico, John A.; Schirle, Markus (2020-06-22). "Manumycin polyketides act as molecular glues between UBR7 and P53". Nature Chemical Biology. 16 (11): 1189–1198. doi:10.1038/s41589-020-0557-2. ISSN 1552-4469. PMC 7572527. PMID 32572277. S2CID 219976949.
  9. ^ Boike, Lydia; Cioffi, Alexander G.; Majewski, Felix C.; Co, Jennifer; Henning, Nathaniel J.; Jones, Michael D.; Liu, Gang; McKenna, Jeffrey M.; Tallarico, John A.; Schirle, Markus; Nomura, Daniel K. (2021-01-21). "Discovery of a Functional Covalent Ligand Targeting an Intrinsically Disordered Cysteine within MYC". Cell Chemical Biology. 28 (1): 4–13.e17. doi:10.1016/j.chembiol.2020.09.001. ISSN 2451-9456. PMC 7854864. PMID 32966806. S2CID 221888024.
  10. ^ Spradlin, Jessica N.; Hu, Xirui; Ward, Carl C.; Brittain, Scott M.; Jones, Michael D.; Ou, Lisha; To, Milton; Proudfoot, Andrew; Ornelas, Elizabeth; Woldegiorgis, Mikias; Olzmann, James A. (July 2019). "Harnessing the anti-cancer natural product nimbolide for targeted protein degradation". Nature Chemical Biology. 15 (7): 747–755. doi:10.1038/s41589-019-0304-8. ISSN 1552-4469. PMC 6592714. PMID 31209351.
  11. ^ Ward, Carl C.; Kleinman, Jordan I.; Brittain, Scott M.; Lee, Patrick S.; Chung, Clive Yik Sham; Kim, Kenneth; Petri, Yana; Thomas, Jason R.; Tallarico, John A.; McKenna, Jeffrey M.; Schirle, Markus; Nomura, Daniel K. (2019-11-15). "Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications". ACS Chemical Biology. 14 (11): 2430–2440. doi:10.1021/acschembio.8b01083. ISSN 1554-8929. PMC 7422721. PMID 31059647.
  12. ^ Henning, Nathaniel J.; Manford, Andrew G.; Spradlin, Jessica N.; Brittain, Scott M.; Zhang, Erika; McKenna, Jeffrey M.; Tallarico, John A.; Schirle, Markus; Rape, Michael; Nomura, Daniel K. (2022-01-19). "Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications". Journal of the American Chemical Society. 144 (2): 701–708. doi:10.1021/jacs.1c03980. ISSN 0002-7863. PMC 8928484. PMID 34994556.
  13. ^ Henning, Nathaniel J.; Boike, Lydia; Spradlin, Jessica N.; Ward, Carl C.; Liu, Gang; Zhang, Erika; Belcher, Bridget P.; Brittain, Scott M.; Hesse, Matthew J.; Dovala, Dustin; McGregor, Lynn M.; Valdez Misiolek, Rachel; Plasschaert, Lindsey W.; Rowlands, David J.; Wang, Feng (April 2022). "Deubiquitinase-targeting chimeras for targeted protein stabilization". Nature Chemical Biology. 18 (4): 412–421. doi:10.1038/s41589-022-00971-2. ISSN 1552-4469. PMC 10125259. PMID 35210618. S2CID 233745282.
  14. ^ Toriki, Ethan S.; Papatzimas, James W.; Nishikawa, Kaila; Dovala, Dustin; McGregor, Lynn M.; Hesse, Matthew J.; McKenna, Jeffrey M.; Tallarico, John A.; Schirle, Markus; Nomura, Daniel K. (2022-11-04). "Rational Chemical Design of Molecular Glue Degraders": 2022.11.04.512693. doi:10.1101/2022.11.04.512693. S2CID 253371370. {{cite journal}}: Cite journal requires |journal= (help)
  15. ^ "Novartis, UC Berkeley join forces for 'undruggable' targets". Fierce Biotech. 28 September 2017. Retrieved 2020-08-27.
  16. ^ Staff, Hyunkyu Michael Lee | (2017-10-02). "UC Berkeley researchers partners with Novartis to develop new cures". The Daily Californian. Retrieved 2020-08-28.
  17. ^ "C&EN's 2019 10 Start-Ups to Watch". Chemical & Engineering News. Retrieved 2020-08-27.
  18. ^ "Vicinitas Therapeutics Launches With $65 Million in Series A Financing to Advance Precision Medicines to Stabilize Key Proteins". Bloomberg.com. 2022-07-28. Retrieved 2022-11-21.
  19. ^ "Daniel Nomura, PhD". 26 January 2021.
  20. ^ "Daniel Nomura receives ASPIRE Award from the Mark Foundation | College of Chemistry".
  21. ^ "NCI Outstanding Investigator Award Recipients - NCI". www.cancer.gov. 2022-11-02. Retrieved 2022-12-04.