Profile picture for user sqi223

Qing-Bai She

Connect

859-323-2851
sqi223@uky.edu
HKRB 417

Positions

  • Professor, Department of Pharmacology & Nutritional Sciences
  • Markey Cancer Center

College Unit(s)

Other Affiliation(s)
  • Markey Cancer Center
  • Pharmacology and Nutritional Sciences Center Affiliated Faculty

Biography and Education

Education

Ph.D., Gifu University
Postdoctoral Fellow, University of Minnesota
Senior Research Scientist, Memorial Sloan-Kettering Cancer Center

Research

Research in our lab focuses on identifying and characterizing oncogenic factors and pathways that drive colorectal cancer (CRC) progression and influence therapeutic outcomes. We employ a combination of molecular cell biology, biochemistry, chemical biology, pharmacology, multiomics, and mouse modeling approaches to elucidate mechanistic basis of redundancy and crosstalk among oncoprotein-activated signaling and metabolic pathways and to understand how their functional interplay promotes CRC progression, metastasis and therapeutic resistance. By leveraging these insights, we seek to develop effective therapeutic strategies to enhance CRC treatment outcomes. Through molecular analysss of mRNA translation states, our work has contributed to the growing body of evidence demonstrating that dysregulated mTORC1/4E-BP1-mediated translational control plays a critical role in cell proliferation, survival, CRC progression, and metastasis, as well as in modulating cancer cell sensitivity to upstream kinase-targeted therapies. Specifically, we identify 4E-BP1 as a critical node integrating the oncogenic effects of the PI3K/AKT and RAS/RAF/MEK/ERK pathways during CRC progression. Furthermore, we have identified and developed a new class of natural product-based small-molecular inhibitors with unique mechanisms of action, targeting translational control in CRC and other types of cancer. Recently, our group identified two novel splice variants of neuropilin-1 (NRP1) that aggressively promote CRC metastasis by activating endosomal signaling. Additionally, we uncovered a novel role of spermine synthase (SMS), a polyamine biosynthetic enzyme, as a key metabolic regulator that facilitates CRC tumorigenesis through cooperation with MYC oncogenic signaling. We are currently further characterizing the role of NRP1 variants in driving CRC progression, metastasis, and therapeutic resistance, as well as investigating the biological and therapeutic consequences of SMS inhibition in CRC tumorigenesis. 

Selected Publications

  1. Cao Y, Ye Q, Ma M, She QB. Enhanced bypass of PD-L1 translation reduces the therapeutic response to mTOR kinase inhibitors. Cell Reports, 42:112764, 2023. PMCID: PMC10491412
  2. Hong, Liu T, Wan L, Fa P, Kumar P, Cao Y, Prasad C, Qiu Z, Liu J, Wang H, Li Z, Wang QE, Guo P, Guo D, Yilmaz AS, Lu L, Papandreou I, Jacob NK, Yan C, Zhang X, She QB, Ma Z, Zhang J. Targeting squalene epoxidase interrupts homologous recombination via the ER stress response and promotes radiotherapy efficacy. Cancer Res, 82:1298-1312, 2022. PMCID: PMC8983553
  3. Guo Y, Ye Q, Deng P, Cao Y, He D, Zhou Z, Wang C, Zaytseva YY, Schwartz CE, Lee EY, Evers BM, Morris AJ, Liu S, She QB. Spermine synthase and MYC cooperate to maintain colorectal cancer cell survival by convergent repression of Bim expression. Nat Commun, 11:3243, 2020. PMCID: PMC7320137
  4. Huang X, Ye Q, Chen M, Li A, Mi W, Fang Y, Zaytseva YY, O’Connor KL, Vander Kooi CW, Liu S, She QB. N-glycosylation-defective splice variants of neuropilin-1 promote metastasis by activating endosomal signals. Nat Commun, 10:3708, 2019. PMCID: PMC6697747 (selected by Faculty 1000 rated exceptional)
  5. Zhang Y, Ye Q, Ponomareva LV, Liu Y, Cao Y, Cui Z, Van Lanen, SG, Voss SR, She QB*, Thorson JS*. Total synthesis of griseusins and elucidation of the griseusin mechanism of action. Chem Sci, 10:7641-7648, 2019. PMCID: PMC6755659 (Edge Article; *Co-corresponding author)
  6. Ye Q, Zhang Y, Cao Y, Wang X, Guo Y, Chen J, Horn J,  Ponomareva LV, Chaiswing L, Shaaban KA, Wei Q, Anderson BD, St Clair KD, Zhu H, Leggas M, Thorson JS, She QB. Frenolicin B targets peroxiredoxin 1 and glutaredoxin 3 to trigger ROS/4E-BP1-mediated antitumor effects. Cell Chem Biol 26:366-377, 2019. PMCID: PMC6557261. (Featured Article
  7. Wang J, Ye Q, Cao Y, Guo Y, Huang X, Mi W, Liu S, Wang C, Yang HS, Zhou BP, Evers BM, She QB. Snail determines the therapeutic response to mTOR kinase inhibitors by transcriptional repression of 4E-BP1. Nat Commun 8:2207, 2017. PMCID: PMC5738350
  8. 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 6:13962-13977, 2015. PMCID: PMC4546444. (Priority Research Paper)
  9. 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 5:6015-6027, 2014. PMCID: PMC4171609
  10. 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 33:1828-1839, 2014. PMCID: PMC3966979
  11. 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 18:39-51, 2010. PMCID: PMC3286650
  12. 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 70:6804-6814, 2010.
  13. 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 3:e3065, 2010.
  14. Rosen N, She QB.  AKT and cancer--is it all mTOR?  Cancer Cell 10:254-256, 2006.
  15. 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 8:287-297, 2005.
  16. 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 9:4340-4346, 2003.
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