Dr. Ke Yu is a Professor of Cancer Pharmacology and Drug Discovery at Fudan University School of Pharmacy. Prior to Fudan in 2011, Dr Yu served as Princ Res Sci III at Wyeth Research (1996-2010), Associate Fellow at Novartis Pharma (1992-1996). Dr Yu’s research has focused on cancer therapy R&D providing biology leadership in advancing numerous first-in-class discovery projects. Dr Yu was a recipient of four R&D achievement awards by Wyeth Research (2004-2009) and was a recipient of ACS Heroes of Chemistry (2008) in recognition of achievement in development of TORISEL/CCI-779, a first-in-class mTOR inhibitor for treatment of cancer. Dr Yu authored over 60 publications in these research areas.
At Fudan School of Pharmacy, Dr Yu’s lab is working on 1) drug discovery programs targeting signaling kinases; 2) validation and drug discovery targeting several priority cell surface cancer genes; 3) current strategy include small molecule chemical inhibitors and large molecule biotherapeutics.
Drug discovery programs targeting signaling kinases; Validation and drug discovery targeting several priority cell surface cancer genes; Current strategy include small molecule chemical inhibitors and large molecule biotherapeutics.
Education & Academic Training
Postdoctoral Fellow (4/1991-8/1992) Cornell University Medical College, New York, NY
Postdoctoral Fellow (3/1988-10/1990) Massachusetts Institute of Technology, Cambridge, MA
Doctor of Philosophy (10/1982-3/1988) University of Chicago, Chicago, IL
Graduate student (1/1982-10/1982) Fudan University, Shanghai
Bachelor of Science (1/1982) Shanghai Normal University, Shanghai
Professional Experiences
Professor (3/2011-Present) Cancer Pharmacology, Fudan University School of Pharmacy, Shanghai
Vice President of Biology (4/2010-12/2010) Sundia MediTech Inc., Shanghai
Princ Res. Scientist III (7/1996-3/2010) Oncology Research, Wyeth Research, Pearl River, NY
Associate Fellow (9/1992-6/1996) Oncology Research, Novartis Pharmaceutical, East Hanover, NJ
Teaching Activities
Recent Progress on Pharmaceutical Research
Modern Drug Discovery
Drug Research Process & Management
Recent Projects
1. Exploratory research on cancer therapy target validation (2012-ongoing).
2. Discovery and preclinical development of a novel tissue factor (TF) monoclonal antibody drug-conjugate for cancer treatment (2012-ongoing).
3. Preclinical and clinical research of SCC-31, a novel and highly selective mTOR kinase small molecule inhibitor for treatment of solid caners (2013-2015, IND 2015), out-licensed 2015.
4. The role and mechanism of mTOR in regulating ATP citrate lyase in tumor metabolism (2014-2017).
5. Novel Smoothened inhibitors for therapeutic targeting of na?ve and drug-resistant hedgehog pathway-driven cancers (2012-2015).
6. Preclinical pharmacology of a novel dual inhibitor of oncogenic c-MET and EML4-ALK (2012-2014, IND 2014).
7. Discovery of novel & highly selective mTOR kinase inhibitors (2011-2013).
Honors & Awards
1. Fudan University School of Pharmacy “Dean’s Award” and “Research Excellence Award” (2017)
2. Fudan University School of Pharmacy “Dean’s Award” (2016)
3. The “Scientific Chinese Award” (2016)
4. American Chemical Society "2008 Heroes of Chemistry" Award (2008)
5. Wyeth Research "Development Track Achievement Award" (2009)
6. Wyeth Research "Development Track Achievement Award" (2008)
7. Wyeth Research "Development Team Award (2004)
8. National Institute of Health Postdoctoral Fellowships (1988-1992)
9. University of Chicago Graduate Student Scholarship (10/1982-3/1988)
Memberships
American Association of Science
American Association of Cancer Research
Selected Publications
1. Toral-Barza L, Zhang WG, Huang X, McDonald LA, Salaski EJ, Barbieri LR, Ding WD, Krishnamurthy G, Hu YB, Lucas J, Bernan VS, Cai P, Levin JI, Mansour TS, Gibbons JJ, Abraham RT, Yu K. Discovery of lactoquinomycin and related pyranonaphthoquinones as potent and allosteric inhibitors of AKT/PKB: mechanistic involvement of AKT catalytic activation loop cysteines. Mol Cancer Ther. 2007; 6:3028-38
2. He H, Janso JE, Yang HY, Bernan VS, Lin SL, Yu K. Culicinin D, an Antitumor Peptaibol Produced by the Fungus Culicinomyces clavisporus, Strain LL-12I252. J Nat Prod. 2007; 69(5):736-41
3. Shor B, Zhang WG, Toral-Barza L, Lucas J, Abraham RT, Gibbons J, Yu K. A new pharmacological action of CCI-779 involves FKBP12-independent inhibition of mTOR kinase activity and profound repression of global protein synthesis. Cancer Res. 2008; 68:2934-43
4. Yu K, Toral-Barza L, Shi C, Zhang WG, Lucas J, Shor B, Kim J, Verheijen J, Curran K, Malwitz DJ, Cole DC, Ellingboe J, Ayral-Kaloustian S, Mansour TS, Gibbons JJ, Abraham RT, Nowak P, Zask A. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res. 2009; 69:6232-40
5. Zask A, Verheijen JC, Curran K, Kaplan J, Richard DJ, Nowak P, Malwitz DJ, Brooijmans N, Bard J, Svenson K, Lucas J, Toral-Barza L, Zhang WG, Hollander I, Gibbons JJ, Abraham RT, Ayral-Kaloustian S, Mansour TS, Yu K. ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines. J Med Chem. 2009; 52:5013-16
6. Nowak P, Cole DC, Brooijmans N, Bursavich MG, Curran KJ, Ellingboe JW, Gibbons JJ, Hollander I, Hu Y, Kaplan J, Malwitz DJ, Toral-Barza L, Verheijen JC, Zask A, Zhang WG, Yu K. Discovery of Potent and Selective Inhibitors of the Mammalian Target of Rapamycin (mTOR) Kinase. J Med Chem. 2009; 52:7081-89
7. Gibbons JJ, Abraham RT, Yu K. Mammalian Target of Rapamycin: Discovery of Rapamycin Reveals a Signaling Pathway Important for Normal and Cancer Cell Growth. Seminars in Oncology 2009; 36:3-17
8. Shor B, Gibbons JJ, Abraham RT, Yu K. Targeting mTOR globally in cancer: Thinking beyond rapamycin. Cell Cycle 2009; 8:3831-37
9. Yu K, Shi C, Toral-Barza L, Lucas J, Shor B, Kim JE, Zhang WG, Mahoney R, Gaydos C, Tardio L, Kim SK, Conant R, Curran K, Kaplan J, Verheijen J, Ayral-Kaloustian S, Mansour TS, Abraham RT, Zask A, and Gibbons JJ. Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2. Cancer Res. 2010; 70:621-31
10. Zask A, Kaplan J, Verheijen JC, Richard DJ, Curran K, Brooijmans N, Bennett EM, Toral-Barza L, Hollander I, Ayral-Kaloustian S, Yu K. Morpholine derivatives greatly enhance the selectivity of mammalian target of rapamycin (mTOR) inhibitors. J Med Chem. 2009; 52:7942-45
11. Ayral-Kaloustian S, Gu J, Lucas J, Cinque M, Gaydos C, Zask A, Chaudhary I, Wang J, Di L, Young M, Ruppen M, Mansour TS, Gibbons JJ, Yu K. Hybrid Inhibitors of Phosphatidylinositol-3-Kinase (PI3K) and the Mammalian Target of Rapamycin (mTOR): Design, Synthesis, and Superior Antitumor Activity of Novel Wortmannin-Rapamycin Conjugates. J Med Chem. 2010; 53:452-59
12. Shor B, Wu J, Shakey Q, Toral-Barza L, Follettie M, Yu K. Requirement of mTOR kinase for the regulation of Maf1 phosphorylation and control of RNA polymerase III-dependent transcription in cancer cells. J Biol Chem. 2010; 285:15380-92
13. Eng C, Yu K, Lucas J, White E, Abraham RT. Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci Signal. 2010; 3(119):ra31
14. Yu K and Toral-Barza L. Biochemical and pharmacological inhibition of mTOR by rapamycin and an ATP-competitive mTOR inhibitor. Methods Mol Biol. 2012;821:15-28
15. Gopalsamy A, Bennett EM, Shi M, Zhang WG, Bard J, Yu K. Identification of pyrimidine derivatives as hSMG-1 inhibitors. Bioorg Med Chem Lett. 2012; 22:6636-41
16. Meng L, Shu M, Chen Y, Yang D, He Q, Zhao H, Feng Z, Liang C, Yu K. A novel lead compound CM-118: antitumor activity and new insight into the molecular mechanism and combination therapy strategy in c-Met- and ALK-dependent cancers. Cancer Biol Ther. 2014; 15:721-34
17. Chen Y, Qian J, He Q, Zhao H, Toral-Barza L, Shi C, Zhang X, Wu J, Yu K. mTOR complex-2 stimulates acetyl-CoA and de novo lipogenesis through ATP citrate lyase in HER2/PIK3CA-hyperactive breast cancer. Oncotarget 2016; 7:25224-40
18. Qian J, Chen Y, Meng T, Ma L, Meng L, Wang X, Yu T, Zask A, Shen J, Yu K. Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer. Oncotarget 2016; 7:67071-86
19. Zhang X, Li Q, Zhao H, Ma L, Meng T, Qian J, Jin R, Shen J, Yu K. Pathological expression of tissue factor confers promising antitumor response to a novel therapeutic antibody SC1 in triple negative breast cancer and pancreatic adenocarcinoma. Oncotarget 2017; 8:59086-102
20. Li Q, Zhao H, Zhang X, Lang H, Yu K. Novel Smoothened inhibitors for therapeutic targeting of na?ve and drug-resistant hedgehog pathway-driven cancers. Acta Pharmacologica Sinica 2018 May 18. doi: 10.1038/s41401-018-0019-5. [Epub ahead of print]
Recent Patents
1. Benzimidazole compound with antitumour activity as well as preparation method and application thereof, ZL201310139335.7
2. Benzimidazole amide compound as well as preparation method and application thereof, ZL201310186206.3
3. Pyridopyrimidine or pyrimidopyrimidine compound, preparation method, pharmaceutical composition, and use thereof, ZL201310068888.8
4. Tissue factor-targeted monoclonal antibodies, preparation method, and use thereof, PCT/CN2017/074163
5. Tissue factor-targeted antibody-drug conjugates, PCT/CN2017/087779
