Tsui-Fen Chou, Ph.D.

Tsui-Fen Chou, PhD

Assistant Professor of Pediatrics, David Geffen School of Medicine at UCLA
Division of Medical Genetics, Harbor-UCLA Medical Center

Contact

Developing new therapeutic targets for cancer

Research Description

Dr. Chou's lab employs a combination of chemical biology, quantitative proteomics, high throughput, high-content screenings, mutational analysis, and biochemical reconstitution to study the molecular mechanisms of protein function. Her research endeavors include identifying physiological substrates of an enzyme of unknown function, enzymatic and kinetic analysis of enzyme activity to identify key amino acid residues and developing small molecule inhibitors for targeted therapy. Her current focus is illuminating the mechanisms by which p97/VCP ATPase orchestrates two major protein clearance pathways, proteasome and autophagy, and regulates the activity of proteins involved in apoptosis. Her work has demonstrated that p97 interacting proteins influence the potency of p97 inhibitors. Dr. Chou is using novel p97 inhibitors in combination with genetic inhibition by RNAi or a dominant negative p97 mutant in proteomic experiments to identify substrates and investigate cell biological functions of p97. This work will discern underlying mechanisms that may lead to novel therapeutic targets and agents for cancer and neurodegenerative disease.
Theme Groups
Research Interests

Education

  • BS, 1999, School of Pharmacy, National Taiwan University, Taipei, Taiwan
  • PhD, 2006, University of Minnesota, Twin Cities

Recent and/or Significant Publications

  1. Gui, L., Zhang, X., Li, K., Frankowski, K.J., Li, S., Wong, D.E., Moen, D.R., Porubsky, P.R., Lin, H Lin, H.J., Schoene, F.J., and Chou, T.-F. “Evaluating p97 inhibitor analogues for potency against p97-p37 and p97-Npl4-Udf1 complexes” ChemMedChem 2016; 11(9): 953-957 PMID: 27043824
  2. Zhang X, Gui L, Zhang X, Bulfer SL, Sanghez V, Wong DE, Lee Y, Lehmann L, Lee JS, Shih PY, Lin HJ, Iacovino M, Weihl CC, Arkin MR, Wang Y, Chou T-F. “Altered cofactor regulation with disease-associated p97/VCP mutations.” Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):E1705-14, PMID: 25775548
  3. Fang, C., Gui, L., Zhang, X., Moen, D.R., Li, K., Frankowski, K. J., Lin, H.J., Schoene, F.J., and Chou, T.-F “Evaluating p97 inhibitor analogues for their domain-selectivity and potency against the p97-p47 complex” ChemMedChem, 2015, 10, 52-56. (PMID: 25377500)
  4. Chou, T.-F, Bulfer SL, Weihl CC, Li K, Lis LG, Walters MA, Schoenen FJ, Lin HJ, Deshaies RJ, Arkin MR. “Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains.” J Mol Biol. 2014 Jul 29;426(15):2886-99. PMID: 24878061
  5. Kato, M., Chou, T.-F, Yu, C.Z., Demodena, J., and Sternberg, P.W. “"LINKIN, a new transmembrane protein necessary for cell adhesion” eLife. 2014, e04449. (PMID:25437307)
  6. Chou, T.-F, Bulfer SL, Weihl CC, Li K, Lis LG, Walters MA, Schoenen FJ, Lin HJ, Deshaies RJ, Arkin MR. “Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains.” J Mol Biol. 2014 Jul 29;426(15):2886-99. PMID: 24878061
  7. Kato, M., Chou, T.-F, Yu, C.Z., Demodena, J., and Sternberg, P.W. “"LINKIN, a new transmembrane protein necessary for cell adhesion” eLife. 2014, e04449. (PMID:25437307)
  8. Chou, T.-F*., Li, K., Frankowski, K., Schoenen, F. J., and Deshaies, R. J*. “Structure-Activity Relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase” ChemMedChem. 2013, 8,297-312
  9. Chou, T.-F.*, Brown, S. J., Minond, D., Nordin, B.E., Li, K., Jones, A.C., Chase, P., Porubsky, P. R., Stoltz, B.M., Schoenen, F. J., Patricelli, M.P., Hodder, P., Rosen, H., and Deshaies, R. J*. “Reversible inhibitor of p97, DBeQ, impairs both ubiquitin-dependent and autophagic protein clearance pathways” Proc. Natl. Acad. Sci. USA. 2011, 108, 4834 - 4839.
  10. Chou, T.-F.*, and Deshaies, R. J*. “Quantitative cell-based protein degradation assays to identify and classify drugs that target the ubiquitin-proteasome system. J. Biol. Chem. 2011, 286, 16546 - 16554