Ph.D., Gifu University
Postdoctoral Fellow, University of Minnesota
Senior Research Scientist, Memorial Sloan-Kettering Cancer Center
Research in my lab focuses on molecular mechanisms of colorectal cancer (CRC) progression and drug resistance. In particular, our work is aimed at understanding the mechanistic basis of redundancy in oncoprotein-activated signaling pathways in CRC and how functional crosstalk among these pathways alters the therapeutic response of CRC. We have recently discovered that deregulated cap-dependent mRNA translation plays a critical role in integrating the oncogenic actions of the PI3K/AKT/mTOR and RAS/RAF/MEK/ERK signaling pathways for maintenance of tumor growth and metastatic progression of CRC, thereby altering the sensitivity of CRC to targeted therapy. We employ a combination of molecular, cellular, biochemical, genetic, pharmacologic, imaging, bioinformatic, animal and clinical association approaches to decipher the transcriptional and post-transcriptional mechanisms controlling gene expression and pathways important for the malignant transformation and metastatic progression of CRC, with the ultimate goal of developing novel biomarkers and therapies for improving the diagnosis and treatment of this disease. In addition, we are also interested in developing nature product-based small molecular inhibitors for targeting translational control of CRC and potentially other major cancers.
1. ACS IRG85-001-22
2. UK CCTS KL2TR000116
1. Mi W, Ye Q, Liu S, She QB. AKT inhibition overcomes rapamycin resistance by enhancing the repressive function of PRAS40 on mTORC1/4E-BP1 axis. Oncotarget 2015 Apr 23. [Epub ahead of print]
2. Hoff JT, Baldwin LA, Lefringhouse J, Zhang M, Liu Z, Erfani S, She QB, Jia C, Ueland FR, van Nagell JR, Wang C, Xu M, Kaetzel DM, Liu C, Luo J, Drapkin R, Zhou BP, Yang XH. CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling. Oncotarget 2014; 15: 12203-17.
3. Wang J, Ye Q, She QB. New insights into 4E-BP1-regulated translation in cancer progression and metastasis. Cancer Cell & Microenvironment 2014; 1: e331.
4. Nandurkar N, Zhang J, Ye Q, Ponomereva LV, She QB, Thorson JS. The identification of perillyl alcohol glycosides with improved antiproliferative activity. J Med Chem 2014; 57: 7478-84.
5. Cai W, Ye Q, She QB. Loss of 4E-BP1 function induces EMT and promotes cancer cell migration and invasion via translational activation of snail. Oncotarget 2014; 5: 6015-6027.
6. Ye Q, Cai W, Zhen Y, Evers BM, She QB. ERK and AKT signaling cooperate to translationally regulate survivin expression for metastatic progression of colorectal cancer. Oncogene 2014; 33: 1828-1839. (doi:10.1038/onc.2013.122; published online Apr 29, 2013)
7. Ye Q, She QB. Integration of AKT and ERK signaling pathways in cancer: biological and therapeutic implications. J Pharmacol Clin Toxicol 2013; 1: 1009.
8. Zhang Y, Wang X, Sunkara M, Ye Q, Ponomareva LV, She QB, Morris AJ, Thorson JS. A diastereoselective oxa-Pictet-Spengler-based strategy for (+)-frenolicin B and epi-(+)-frenolicin B synthesis. Org Lett 2013; 15: 5566-9.
9. Liu Y, Liu F, Yu H, Zhao X, Sashida G, Deblasio A, Harr M, She QB, Chen Z, Lin HK, Di Giandomenico S, Elf SE, Yang Y, Miyata Y, Huang G, Menendez S, Mellinghoff IK, Rosen N, Pandolfi PP, Hedvat CV, Nimer SD. Akt phosphorylates the transcriptional repressor bmi1 to block its effects on the tumor-suppressing ink4a-arf locus. Sci Signal 2012; 5: ra77.
10. Hanrahan AJ, Schultz N, Westfal ML, Sakr RA, Giri DD, Scarperi S, Janikariman M, Olvera N, Stevens EV, She QB, Aghajanian C, King TA, de Stanchina E, Spriggs DR, Heguy A, Taylor BS, Sander C, Rosen N, Levine DA, Solit DB. Genomic complexity and AKT-dependence in serous ovarian cancer. Cancer Discov 2012; 2: 56-67.
11. Xing F, Persaud Y, Pratilas CA, Taylor BS, Janakiraman M, She QB, Gallardo H, Liu C, Merghoub T, Hefter B, Dolgalev I, Viale A, Heguy A, De Stanchina E, Cobrinik D, Bollag G, Wolchok J, Houghton A, Solit DB. Concurrent loss of the PTEN and RB1 tumor suppressors attenuates RAF dependence in melanomas harboring (V600E)BRAF. Oncogene 2012; 31: 446-457.
12. She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, Solit, DB, Rosen N. 4E-BP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell 2010; 18: 39-51.
13. Halilovic E, She QB, Ye Q, Pagliarini R, Sellers WR, Solit DB, Rosen N. PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and mutant KRAS signaling. Cancer Res 2010; 70: 6804-6814.
14. Cherrin C, Haskell KM, Howell B, Jones R, Leander KR, Robinson, R, Watkins A, Bilodeau M, Hoffman J, Sanderson P, Hartman G, Mahan E, Prueksaritanont T, Jiang G, She QB, Rosen N, Sepp-Lorenzino L, DeFeo-Jones D, Huber HE. An allosteric Akt inhibitor effectively blocks Akt signaling and tumor growth with only transient effects on glucose and insulin levels in vivo. Cancer Biol Ther 2010; 9: 493-503.
15. She QB, Chandarlapaty S, Ye Q, Lobo J, Haskell KM, Leander KR, DeFeo-Jones D, Huber HE, Rosen N. Breast tumor cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signaling. PLoS ONE 2008; 3: e3065.
16. Nelander S, Wang WQ, Nilsson B, She QB, Pratilas C, Rosen N, Gennemark P, Sander C. Models from experiments: combinatorial drug perturbations of cancer cells. Mol Syst Biol 2008; 4: 216.
17. Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmstrom P, Memeo L, Isola J, Bendahl PO, Rosen N, Hibshoosh H, Ringner M, Borg A, Parsons R. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci USA 2007; 104: 7564-7569.
18. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 2006; 66: 1500-1508.
19. Rosen N, She QB. AKT and cancer--is it all mTOR? Cancer Cell 2006; 10: 254-256.
20. She, QB, Solit DB, Ye Q, O'Reilly KE, Lobo J, Rosen N. The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells. Cancer Cell 2005; 8: 287-297.
21. She QB, Solit D, Basso A, Moasser MM. Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells can be overcome through restoration of PTEN function or pharmacologic modulation of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling. Clin Cancer Res 2003; 9: 4340-4346.
22. She QB, Ma WY, Wang M, Kaji A, Ho CT, Dong Z. Inhibition of cell transformation by resveratrol and its derivatives: differential effects and mechanisms involved. Oncogene 2003; 22: 2143-2150.
23. She QB, Chen N, Bode AM, Flavell RA, Dong Z. Deficiency of c-Jun-NH(2)-terminal kinase-1 in mice enhances skin tumor development by 12-O-tetradecanoylphorbol-13-acetate. Cancer Res 2002; 62: 1343-1348.
24. She QB, Ma WY, Dong Z. Role of MAP kinases in UVB-induced phosphorylation of p53 at serine 20. Oncogene 2002; 21: 1580-1589.
25. She QB, Ma WY, Zhong S, Dong Z. Activation of JNK1, RSK2, and MSK1 is involved in serine 112 phosphorylation of Bad by ultraviolet B radiation. J Biol Chem 2002; 277: 24039-24048.
26. She QB, Huang C, Zhang Y, Dong Z. Involvement of c-jun NH(2)-terminal kinases in resveratrol-induced activation of p53 and apoptosis. Mol Carcinog 2002; 33: 244-250.
27. She QB, Bode AM, Ma WY, Chen NY, Dong Z. Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. Cancer Res 2001; 61: 1604-1610.
28. She QB, Chen N, Dong, Z. ERKs and p38 kinase phosphorylate p53 protein at serine 15 in response to UV radiation. J Biol Chem 2000; 275: 20444-20449.