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Bing Xia, Ph.D.

Associate Professor

Division of Radiation Cancer Biology

Tel:    732-235-7410




    • BS 1992 - Wuhan University , P.R. China
    • Ph.D. 2001 - UMDNJ-Robert Wood Johnson Medical School
    • Postdoctoral Training: Dana-Farber Cancer Institute and Harvard Medical School

Research Interests:

DNA repair, homologous recombination, breast cancer, Fanconi anemia

DNA damages constantly occur inside the cell due to endogenous metabolic processes and/or exposure to external genotoxic agents. Among the various types of lesions that exist are double-strand breaks (DSBs), which, if unrepaired, can elicit chromosomal translocations and loss of chromosomal segments. These severe genomic aberrations often cause cell cycle arrest or cell death, but can also promote cellular transformation and evolution of cancer cells. Homologous recombination (HR) is a major mechanism to repair DSBs, and is also the only error-free process fulfilling this function. The two major breast cancer susceptibility proteins, BRCA1 and BRCA2, are critical to HR as well as cellular mechanisms that trigger certain cell cycle checkpoints following DNA damage. BRCA2, which controls the function of the recombination enzyme RAD51, is central to HR and therefore particularly important in the repair of DSBs by HR. A fraction of BRCA1 and BRCA2 interact with each other in the cell nucleus and likely function cooperatively in certain steps of DSB repair.

BRCA1 mutations almost exclusively predispose carriers to female breast cancer and ovarian cancer, whereas mutations in BRCA2 can lead to tumor development in a broader spectrum of organs including female breast, ovary, male breast, prostate, and pancreas. In addition, BRCA2 is also a Fanconi anemia (FA) protein. FA is a rare, recessive genetic syndrome characterized by certain congenital abnormalities, progressive bone marrow failure, and cancer susceptibility. The biological hallmark of FA cells is hypersensitivity to DNA interstrand crosslinks, which are likely processed into DSBs and subsequently repaired, at least in part, by HR. FA patients with BRCA2 deficiency tend to have distinct, severe phenotypes featuring the development of “embryonal” cancers such as medulloblastoma and Wilms tumor at very young ages.

We cloned a major BRCA2-binding protein, PALB2, which stands for “partner and localizer of BRCA2”. We found that PALB2 controls the intra-nuclear localization/chromatin association of BRCA2 and its repair as well as checkpoint functions. Importantly, together with others, we further demonstrated that the PALB2 gene, like BRCA2 , is also mutated in breast cancer and Fanconi anemia. Moreover, the phenotypes of FA patients with PALB2 mutations are identical to those with BRCA2 mutations, suggesting that PALB2 is of equal importance in terms of fundamental biological functions. Moreover, we recently found that PALB2 also directly interacts with BRCA1 and in such a way links the two BRCA proteins to form the central breast cancer suppression pathway.

Our lab is interested in the following research themes: 1) biochemical purification of the BRCA1/PALB2/BRCA2 complexes under different conditions and in different cell types, aiming to identify more players and reveal the dynamics and potential tissue specificity of the BRCA tumor suppression network; 2) structure-function analysis of BRCA2 and PALB2 in HR, DSB repair, interstrand crosslink repair, and DNA damage checkpoint response; 3) mechanistic details of the interplays among BRCA1, BRCA2, PALB2, RAD51 and other components of the network; 4) PALB2 - and BRCA2 - knockout and knockin mouse models; 5) identification and validation of clinically relevant BRCA2 and PALB2 mutations in collaborations with human genetics groups; and 6) trying to identify genes in the FA/BRCA network that may serve as new biomarkers for rational drug intervention and radiation therapy. Through these studies, we aim to discover the link(s) between the molecular actions of these proteins in the DNA damage response and their abilities to suppress tumorigenesis, and hopefully contribute to the clinical management and/or treatment of afore-mentioned diseases.

Selected publications:

    • Zhang, F*, Ma, J*, Wu, J*, Ye, L, Cai, H, Xia, B # and Yu, X. # (2009) PALB2 Links BRCA1 and BRCA2 in the DNA Damage Response. Curr Biol 19: 524–529. ( # co-corresponding authors)
    • Sobhian, B., Shao, G., Lilly, D.R., Culhane, A., Moreau, L., Xia, B., Livingston , D.M. and Greenberg, R.A. (2007) Rap80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. Science 316:1198-1202.
    • Tischkowitz, M.*, Xia, B.*, Sabbaghian, N., Reis-Filho, J., Hamel, N., Li, G., van Beers, E., Li, L., Khalil, T., Quenneville, L., Omeroglu, A., Poll, A., Lepage, P., Wong, N., Nederlof, P., Ashworth, A., Rahman, N., Tonin, P.N., Narod, S.A., Livingston, D.M. and Foulkes, W.D. (2007) Analysis of PALB2/FANCN-associated breast cancer families. Proc Natl Acad Sci USA 104:6788-6793
    • Erkko, H.*, Xia, B.*, Nikkil, J., Schleutker, J., Syrjkoski, K., Mannermaa, A., Kallioniemi, A., Pylks, K., Karppinen, S., Rapakko, K., Miron, A., Sheng, Q., Li, G., Mattila, H., Bell, D.W., Haber, D.A., Grip, M., Jukkola-Vuorinen, A., Mustonen, A., Kere, J., Altonen, L.A., Kosma, V., Kataja, V., Soini, Y., Drapkin, R.I., Livingston, D.M. and Winqvist, R. (2007) A recurrent mutation in PALB2 in Finnish cancer families. Nature 446: 316-319
    • Xia, B.*, Dorsman, J.C.*, Ameziane, N., de Vries, Y., Rooimans, M.A., Sheng, Q. , Pals, G., Errami, A., Gluckman, E., Llera, J., Wang, W., Livingston, D.M. , Joenje, H. and de Winter, J.P . (2007) Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nature Genet 39:165-167
    • Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F.J., and Livingston , D.M. (2006) Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell 22: 719-729
    • Qing, G., Ma, L.C., Khorchid, A., Swapna, G.V., Mal, T.K., Takayama, M.M., Xia, B., Phadtare, S., Ke, H., Acton, T., Montelione, G.T., Ikura, M., and Inouye, M. (2004) Cold-shock induced high-yield protein production in Escherichia coli . Nature Biotechnol 22: 877-882.
    • Qing, G., Xia, B., and Inouye, M. (2004) Enhancement of translation initiation by A/T-rich sequences downstream of the initiation codon in Escherichia coli. J Mol Microbiol Biotechnol 6: 133-144.
    • Xia, B.*, Ke, H.* and Inouye, M. (2003) The role of RbfA in 16S rRNA processing and cell growth at low temperature in Escherichia coli . J Mol Biol 332 : 575-584.
    • Huang, Y.J., Swapna, G.V.T., Rajan, P.K., Ke, H., Xia, B., Shukla, K., Inouye, M. and Montelione G.T. (2003) Solution NMR structure of Ribosome Binding Factor A (RbfA), a cold-shock adaptation protein from Escherichia coli. J Mol Biol 327: 521-536.
    • Xia, B., Ke, H., Jiang, W. and Inouye, M. (2002) The Cold Box stem-loop proximal to the 5'-end of the Escherichia coli cspA gene stabilizes its mRNA at low temperature. J Biol Chem 277 : 6005-6011.
    • Swapna, G.V.T., Shukla, K., Huang, Y.J., Ke, H., Xia, B., Inouye, M. and Montelione, G.T. (2001) Resonance assignments for cold-shock protein ribosome-binding factor A (RbfA) for Escherichia coli . J Biomol NMR 21: 389-390.
    • Xia, B., Etchegaray, J.P. and Inouye, M. (2001) Nonsense mutations in cspA cause ribosome trapping leading to complete growth inhibition and cell death at low temperature in Escherichia coli . J Biol Chem 276:35581-35588.
    • Xia, B., Ke, H. and Inouye, M. (2001) Acquirement of cold sensitivity by a quadruple deletion of cspA family and its suppression by PNPase S1 domain in Escherichia coli . Mol Microbiol 40:179-188.
    • Bae,W., Xia, B., Inouye, M. and Severinov, K. (2000) Escherichia coli CspA-family RNA chaperones are transcription antiterminators. Proc Natl Acad Sci USA 97: 7784-7789.

       * These authors contribute equally to the work.