Bo Xu, M.D., Ph.D.
M.D. The Norman Bethune University of Medical Sciences, Changchun, China (Medicine)
Hematology and Oncology Postdoctoral Research Fellowship, St Jude Children’s Research Hospital, Memphis, TN
After completing his postdoctoral training in the laboratory of Dr. Michael B. Kastan at St. Jude Children’s Research Hospital in Memphis, TN, Dr. Xu joined the Louisiana State University Health Sciences Center in New Orleans, Louisiana as a tenure-track Assistant Professor of Genetics and a member of the Stanley S. Scott Cancer Center. From May 2006 to August 2009, he served as the Principal Investigator and leader of the Laboratory of Molecular Radiobiology in the Department of Biochemistry and Molecular Biology at the Southern Research Institute in Birmingham, Alabama. While there, he also served as an adjunct Associate Professor of Pharmacology and Toxicology at the University of Alabama at Birmingham (UAB) and a member of the UAB Comprehensive Cancer Center. Dr. Xu accepted his current positions at the Houston Methodist Hospital and Research Institute in August 2009.
Dr. Xu’s research team focuses on studying molecular mechanisms that control cellular responses to DNA damage agents. These regulatory events are central to two of the major issues in the field of cancer biology: 1) how and when cancers start and progress, and 2) determinants of sensitivity of tumors to therapeutic interventions. In terms of cancer causation, the critical role for DNA damage responses is demonstrated by the fact that a number of human cancer susceptibility syndromes are caused by inherited mutations affecting proteins involved in DNA damage responses. For example, inherited mutations in damage-response genes can lead to skin cancers (Xeroderma pigmentosum genes), leukemia and lymphoma (ATM, NBS1 and Fanconi Anemia genes), breast and ovarian cancers (p53, BRCA1, BRCA2), colon cancers (mismatch repair genes), and brain tumors (p53). The epidemiological observation that exposure to environmental DNA damaging agents contributes to at least 80% of all human cancers further illustrates the importance of these damage responses in cancer causation. Since many cancer therapeutic interventions attempt to kill tumors by targeting the DNA, gene products involved in DNA damage response pathways are also predictably critical for determining therapeutic outcomes. Thus, elucidation of the mechanisms involved in DNA damage response pathways has obvious importance both for understanding cancer causation and for eliciting cancer cures.
DNA damage and repair, cell cycle checkpoints, spindle checkpoint, drug discovery, radiosensitization
Chunying Yang, Mike Lee, Jianwei Hao, Xiaoli Cui, Xiaojing Guo, Caroline Smal, Françoise Bontemps, Shumei Ma, Xiaodong Liu, David Engler, William B. Parker, and Bo Xu. Deoxycytidine kinase regulates the G2/M checkpoint through interaction with Cyclin-Dependent Kinase 1 in response to DNA damage. Nucleic Acids Research 2012 in pres
Chunying Yang, Xi Tang, Xiaojing Guo, Yohei Niikura, Katsumi Kitagawa, Kemi Cui, Stephen T.C. Wong, Li Fu, and Bo Xu. Aurora-B Mediated ATM Serine 1403 Phosphorylation Is Required For Mitotic ATM Activation and the Spindle Checkpoint. Mol Cell. 2011 Nov 18;44(4):597-608. Issue Highlight.
Liu J, Luo S, Zhao H, Liao J, Li J, Yang C, Xu B, Stern DF, Xu X, Ye K. Structural mechanism of the phosphorylation-dependent dimerization of the MDC1 forkhead-associated domain. Nucleic Acids Res. 2012 Jan 10. [Epub ahead of print]
Chunying Yang, Haibo Wang, Yiran Xu, Kathryn Brinkman, Stephen Wong and Bo Xu. The kinetochore protein Bub1 participates in the DNA damage response. DNA Repair (Amst). 2011 Nov 7 [Epub ahead of print].
Sun X, Yang C, Liu H, Wang Q, Wu SX, Li X, Xie T, Brinkman KL, Teh BS, Butler EB, Xu B*, Zheng S* co-corresponding author). Identification and Characterization of a Small Inhibitory Peptide That Can Target DNA-PKcs Autophosphorylation and Increase Tumor Radiosensitivity. Int J Radiat Oncol Biol Phys. 2012 May 15. [Epub ahead of print]
Ishiyama H, Hirayama T, Jhaveri P, Satoh T, Paulino AC, Xu B, Butler EB, Teh BS. Is There an Increase in Genitourinary Toxicity in Patients Treated With Transurethral Resection of the Prostate and Radiotherapy? A Systematic Review. Am J Clin Oncol. 2012 Jun 14. [Epub ahead of print]
Kathryn L. Brinkman, Bin S. Teh, Bo Xu*. A Review of Stereotactic Body Radiation Therapy (SBRT) from the Molecular Radiobiology Perspective. Journal of Radiation Oncology, 2012 in press
Dever SM, Golding SE, Rosenberg E, Adams BR, Idowu MO, Quillin JM, Valerie N, Xu B, Povirk LF, Valerie K. Mutations in the BRCT binding site of BRCA1 result in hyper-recombination. Aging (Albany NY). 2011 May;3(5):515-32.
Chunzhi Zhang, Chunsheng Kang, Ping Wang, Yongzhen Cao, Zhonghong Lv, Shizhu Yu, Guangxiu Wang, Anling Zhang, Zhifan Jia, Lei Han, Chunying Yang, Hiromichi Ishiyama, Bin S. Teh, Bo Xu, Peiyu Pu. MicroRNA-221/-222 regulate radiation sensitivity by targeting the PTEN pathway. International Journal Of Radiation Oncology, Biology and Physics. 2011 May 1;80(1):240-8.
Yuanhong Gao, Hiromichi Ishiyama, Mianen Sun, Kathryn Brinkman, Xiaozhen Wang, Julie Zhu, Weiyuan Mai, Ying Huang, Daniel Floryk, Michael Ittmann, Timothy C. Thompson, E. Brian Butler, Bo Xu, and Bin S. Teh. The alkylphospholipid, perifosine, radiosensitizes prostate cancer cells both in vitro and in vivo. Radiation Oncology. 2011 Apr 15;6(1):39.
Tang X, Hui ZG, Cui XL, Garg R, Kastan MB, Xu B. A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage. Mol Cell Biol. 2008 Apr;28(8):2559-66.
Cariveau MJ, Stackhouse M, Cui XL, Tiwari K, Waud W, Secrist JA 3rd, Xu B. Clofarabine acts as radiosensitizer in vitro and in vivo by interfering with DNA damage response. Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):213-20.
Cariveau MJ, Tang X, Cui XL, Xu B. Characterization of an NBS1 C-terminal peptide that can inhibit ataxia telangiectasia mutated (ATM)-mediated DNA damage responses and enhance radiosensitivity. Mol Pharmacol. 2007 Aug;72(2):320-6
Gasior SL, Wakeman TP, Xu B, Deininger PL. The human LINE-1 retrotransposon creates DNA double-strand breaks. J Mol Biol. 2006 Apr 14;357(5):1383-93.
Xu B, Kastan MB. Analyzing cell cycle checkpoints after ionizing radiation. Methods Mol Biol. 2004;281:283-92.
Wakeman TP, Kim WJ, Callens S, Chiu A, Brown KD, Xu B. The ATM-SMC1 pathway is essential for activation of the chromium[VI]-induced S-phase checkpoint. Mutat Res. 2004 Oct 4;554(1-2):241-51.
Arlt MF, Xu B, Durkin SG, Casper AM, Kastan MB, Glover TW. BRCA1 is required for common- fragile-site stability via its G2/M checkpoint function. Mol Cell Biol. 2004 Aug;24(15):6701-9.
Garg R, Geng CD, Miller JL, Callens S, Tang X, Appel B, Xu B. Molecular cloning and characterization of the catalytic domain of zebrafish homologue of the ataxia-telangiectasia mutated gene. Mol Cancer Res. 2004 Jun;2(6):348-53.
Garg R, Callens S, Lim DS, Canman CE, Kastan MB, Xu B. Chromatin association of rad17 is required for an ataxia telangiectasia and rad-related kinase-mediated S-phase checkpoint in response to low-dose ultraviolet radiation. Mol Cancer Res. 2004 Jun;2(6):362-9.
Lee JH, Xu B, Lee CH, Ahn JY, Song MS, Lee H, Canman CE, Lee JS, Kastan MB, Lim DS. Distinct functions of Nijmegen breakage syndrome in ataxia telangiectasia mutated-dependent responses to DNA damage. Mol Cancer Res. 2003 Jul;1(9):674-81.
Xu B, O'Donnell AH, Kim ST, Kastan MB. Phosphorylation of serine 1387 in Brca1 is specifically required for the Atm-mediated S-phase checkpoint after ionizing irradiation. Cancer Res. 2002 Aug 15;62(16):4588-91.
Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D'Andrea AD. Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Cell. 2002 May 17;109(4):459-72.
Kim ST, Xu B, Kastan MB. Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damage. Genes Dev. 2002 Mar 1;16(5):560-70.
Xu B, Kim St, Kastan MB. Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol. 2001 May;21(10):3445-50.
Lim DS, Kim ST, Xu B, Maser RS, Lin J, Petrini JH, Kastan MB. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature. 2000 Apr 6;404(6778):613-7.