Zhi-Xiang Xu, MD, PhD
Rank: Assistant Professor
Campus Address: WTI 520D
2/2001-11/2004 Postdoctoral Fellow, Department Molecular Pathology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX (Dr. Kun-Sang Chang)
12/2004-11/2009 Assistant Professor (Research), Department of Molecular Therapeutics (Department of Systems Biology), The University of Texas M. D. Anderson Cancer Center, Houston, TX.
11/2009-present Assistant Professor (tenure track), Division of Hematology / Oncology & Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL
The objectives in Dr. Xu's lab are to identify the molecular mechanisms underlying tumor suppressor function and to develop pharmacological agents that can modulate or mimic tumor suppressors for cancer prevention and treatment. Specifically, the lab currently has three research directions:
(1) Tumor suppressor and genomic stability: (A) To investigate mechanisms of how tumor suppressors, such as LKB1 (also known as serine/threonine kinase 11, STK11), PML, and p53, regulate genomic stability; (B) To determine LKB1-related protein signatures and signaling networks under stressed conditions and identify novel LKB1-interacting proteins; (C) To define LKB1 expression (mutation) in tumors and its relationship to patient outcomes and therapeutic response.
(2) Cell death---Autophagy and Necrosis: (A) To determine the role of autophagy in LKB1-mediated genomic stabilization; (B) To screen and characterize genes that regulate autophagy and necrosis in mammalian cells; (C) To determine the role of autophagy and necrosis in tumorigenesis and targeted therapy.
(3) Molecular therapeutics: To develop pharmacologic agents targeting the LKB1-AMPK-mTOR pathway for cancer prevention and treatment.
1. Xu HG, Zhai YX, Chen J, Lu Y, Wang JW, Quan CS, Zhao RX, Xiao X, He Q, Werle KD, Kim HG, Lopez R, Cui R, Liang J, Li YL, Xu ZX. LKB1 reduces ROS-mediated cell damage via activation of p38. Oncogene 2014 Sep 29. doi: 10.1038/onc.2014.315. [Epub ahead of print] PMID: 25263448
2. Jian W, Xu HG, Chen J, Xu ZX, Levitt JM, Stanley JA, Yang ES, Lerner SP, Sonpavde G. 2014. Activity of CEP-9722, a poly (ADP-ribose) polymerase inhibitor, in urothelial carcinoma correlates inversely with homologous recombination repair response to DNA damage. Anticancer Drugs 25: 878-886.
3. Werle KD, Chen J, Xu HG, Zhao RX, Cui R, Liang J, Xu ZX. Liver Kinase B1 regulates the centrosome via PLK1. Cell Death Disease 2014; 5: e1157
4. Lu C, Chen J, Xu HG, Zhou X, He Q, Li YL, Jiang G, Shan Y, Xue B, Zhao RX, Wang Y, Werle KD, Cui R, Liang J, Xu ZX. MIR106B and MIR93 Prevent Removal of Bacteria from Epithelial Cells by Disrupting ATG16L1-Mediated Autophagy. Gastroenterology 2014; 146 (1): 188-99.
5. Zhao RX, Xu ZX. Targeting the LKB1 Tumor Suppressor. Current Drug Targets 2014; 15(1): 32-52
6. Wang Y, Wang JW, Xiao X, Shan Y, Xue B, Jiang G, He Q, Chen J, Xu HG, Zhao RX, Werle KD, Cui R, Liang J, Li YL, Xu ZX. Piperlongumine Induces Autophagy by Targeting p38 Signaling, Cell Death Disease 2013; 4: e824
7. Liu F, Cao J, Sullivian K, Shen J, Ryu B, Xu ZX, Liu X, Cui R. Stat3 targeted therapies overcome the acquired resistance to vemurafenib in melanomas. J Invest Dermatol 2013; 133(8): 2041-9. PMID: 23344460
8. Liu F, Cao J, Lv J, Dong L, Pier E, Xu GX, Wang RA, Xu ZX, Goding C, Cui R. TBX2 expression is regulated by PAX3 in the melanocyte lineage. Pigment Cell Melanoma Res 2013; 26(1): 67-77. PMID: PMC3527652
9. Xiao XX, He Q, Lu C, Werle KD, Zhao RX, Chen J, Davis BC, Cui R, Liang J, Xu ZX. Metformin impairs the growth of LKB1-intact cervical cancer cells. Gynecol Oncol. 2012; 127(1): 249-55.
10. Miki T, Xu ZX, Chen-Goodspeed M, Liu MG, Van Oort-Jansen A, Rea MA, Zhao Z, Cheng CC, Chang KS. PML regulates PER2 nuclear localization and circadian function. EMBO J, 2012; 31(6): 1427-39.
11. Dong L, Li Y, Cao J, Liu F, Pier E, Chen J, Xu Z, Chen C, Wang RA, Cui R. FGF2 regulates melanocytes viability through the STAT3-transactivated PAX3 transcription. Cell Death Differ. 2012; 19(4): 616-22
12. Haridas V, Xu ZX, Kitchen D, Michels P, and Gutterman JU. The anticancer plant triterpenoid, Avicin D, regulates glucocorticoid receptor signaling: Implications for cellular metabolism. PLoS ONE, 2011, 6(11): e28037.
13. Wang S, Wang H, Davis BC, Liang J, Cui R, Chen SJ, Xu ZX. PARP1 inhibitors attenuate AKT phosphorylation via the upregulation of PHLPP1. Biochem Biophys Res Commun. 2011; 412(2): 379-84.
14. Wang H, Haridas V, Gutterman JU, and Xu ZX. Natural triterpenoid avicins selectively induce tumor cell death (Review). Communicative & Integrative Biology 2010; 3(3): 205-208
15. Xu ZX, Ding T, Haridas V, Connolly F, Gutterman JU. A plant triterpenoid, avicin D, induces cell apoptosis by recruitment of Fas and downstream signaling molecules into lipid rafts. PLoS ONE 2009; 4(12):e8532.
16. Haridas V, Nishimura G, Xu Z-X, Connolly F, Hanausek M, et al. Avicin D: A Protein Reactive Plant Isoprenoid Dephosphorylates Stat 3 by Regulating Both Kinase and Phosphatase Activities. PLoS ONE 2009; 4(5): e5578.
17. Pan J, Chen B, Su CH, Xu ZX, Sun L, Lee MH, Yeung SC. Autophagy induced by farnesyltransferase inhibitors in cancer cells. Cancer Biol Ther 2008; 7(10): 1679-1684
18. Zhang C, Li B, Gaikwad A, Haridas V, Xu ZX, Gutterman J, and Duvic M. Avicin D selectively induces apoptosis and downregulates p-STAT-3, bcl-2, and survivin in cutaneous T-cell lymphoma cells. J Invest Dermatol 2008; 128(11): 2728-35.
19. Xu ZX, Liang J, Haridas V, Gaikwad A, Connolly FP, Mills GB, Gutterman JU. A plant triterpenoid induces tumor cell autophagy by activation of AMPK. Cell Death and Differentiation 2007, 14: 1948-1957
20. Liang J, Shao S, Xu ZX, Hennessy B, Ding ZY, Kondo S, Dumont D, Gutterman JU, Walker CL, Slingerland JM, Mills GB. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nature Cell Biology 2007; 9: 218-224
21. Lin SY, Rai R, Li K, Xu ZX, Elledge SJ. BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly. Proc Natl Acad Sci U S A 2005; 102: 15105-9
22. Pan J, She M, Xu ZX, Sun L, Yeung SCJ. Farnesyltransferase inhibitors induce DNA damage via reactive oxygen species in human cancer cells. Cancer Res 2005; 65(9): 3671-3681
23. Xu ZX, Zou WX, Lin P, Chang KS. A role for PML3 in centrosome duplication and genome stability. Mol Cell 2005; 17(5): 721-732
24. Xu ZX, Zhao RX, Ding T, Tran TT, Zhang W, Pandolfi PP, Chang KS. PML4 induces apoptosis by inhibition of Survivin expression. J Biol Chem 2004; 279(3): 1838-1844.
25. Wu WS, Xu ZX, Hittleman WN, Salomoni P, Pandolfi PP, Chang KS. Promyelocytic leukemia protein sensitizes tumor necrosis factor alpha-induced apoptosis by inhibition the NF-kappa B survival pathway. J Biol Chem 2003; 278(14): 12294-304.
26. Xu ZX, Timanova-Atanasova A, Zhao RX, Chang KS. PML colocalizes with and stabilizes the DNA damage response protein TopBP1. Mol Cell Biol 2003; 23(12): 4247-56.
27. Wu WS, Xu ZX, Ran RX, Feng M, Chang KS. Promyelocytic Leukemia Protein PML inhibits Nur77-mediated Transcription through Specific Functional Interaction. Oncogene 2002; 21(24): 3925-33.
28. Wu WS, Xu ZX, Chang KS. Promyelocytic leukemia protein represses A20-mediated transcription. J Biol Chem 2002; 277(35): 31734-9.