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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 damage, oxidative stress, autophagy, breast cancer

DNA damage constantly occurs due to both endogenous metabolic processes and external genotoxic agents. Among the various types of lesions in DNA are double-strand breaks (DSBs), which, if not repaired or inaccurately repaired, can result in loss of chromosomal segments, chromosomal translocations, or other types of genomic alterations. These alterations may 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. BRCA1 and BRCA2 are important tumor suppressor proteins playing essential roles in HR, DSB repair, and cell cycle checkpoint control. Inherited mutations in either gene substantially increase the risk of cancer development, particularly in the breast, ovary and pancreas.

In 2006, we reported the discovery of PALB2 as a major BRCA2 binding partner that controls its DNA damage response functions. Immediately after its discovery, we and others found PALB2 mutations in familial breast cancer and Fanconi anemia (FA), establishing PALB2 as a tumor suppressor and an FA protein in its own right. Subsequently, work from multiple laboratories, including ours, demonstrated that PALB2 also directly interacts with BRCA1 and links BRCA1 and BRCA2 in the HR/DSBR pathway. Later, PALB2 was also found to be mutated in familial pancreas cancer and ovarian cancer, among others, further establishing PALB2 as a BRCA-type tumor suppressor.

More recently, we have shown that PALB2 also participates in cellular redox regulation via direct binding to KEAP1, a sensor of oxidative stress and a powerful negative regulator of NRF2, a master antioxidant transcriptional factor. Interestingly, BRCA1 has also been implicated in the regulation of NRF2-mediated antioxidant response, suggesting that PALB2 and BRCA1 may function together or in parallel to regulate redox homeostasis and that oxidative stress may play a key role in tumor development following the loss of these tumor suppressors. Moreover, we have also found that autophagy, a key intracellular waste disposal, nutrient recycling and oxidative stress mitigation mechanism, may be an important facilitator of PALB2-associated tumor development.

Currently, our laboratory is pursuing the following lines of research: 1) mechanistic analyses of the BRCA1-PALB2-BRCA2 and KEAP1-NRF2 pathways in the DNA damage response and oxidative stress response; 2) mouse models of hereditary breast cancer, focusing on the roles of DNA damage, oxidative stress and autophagy in the cancer development process; and 3) functional characterization of clinically relevant BRCA1, BRCA2 and PALB2 mutations in DNA repair and therapy resistance. Through these studies, we aim to shed light on the molecular mechanisms and developmental path of BRCA/PALB2-associated cancers, and contribute to the prevention and treatment of the diseases.

Selected publications:

  • Lu K, Alcivar AL, Ma J, Foo TK, Zywea S, Mahdi A, Huo Y, Kensler TW, Gatza ML and Xia B. (2017) NRF2 induction supporting breast cancer cell survival is enabled by oxidative stress-induced DPP3-KEAP1 interaction. Cancer Res. In press.

  • Anantha RW, Simhadri S, Foo TK, Miao S, Liu J, Shen Z, Ganesan S and Xia B. (2017) Functional and mutational landscapes of BRCA1 for homology-directed repair and therapy resistance. eLife 2017;10.7554/eLife.21350

  • Foo TK, Tischkowitz M, Simhadri S, Boshari T, Zayed N, Burke KA, Berman SH, Blecua P, Riaz N, Huo Y, Ding YC, Neuhausen SL, Weigelt B, Reis-Filho JS, Foulkes WD and Xia B. (2017) Compromised BRCA1-PALB2 interaction is associated with breast cancer risk. Oncogene [Epub ahead of print] doi: 10.1038/onc.2017.46.
  • Orthwein A, Noordermeer SM, Wilson MD, Landry S, Enchev RI, Sherker A, Munro M, Pinder J, Salsman J, Dellaire G, Xia B, Peter M and Durocher D. (2015) A mechanism for the suppression of homologous recombination in G1 cells. Nature 528:422-6.
  • Simhadri S, Peterson S, Patel D, Huo Y, Cai H, Miller S, Ludwig T, Ganesan S, Bhaumik M, Bunting S, Jasin M and Xia B. (2014) Male fertility defect associated with a disruption of BRCA1-PALB2 interaction in mice. J Biol Chem 289:24617-29.
  • Huo Y, Cai H, Teplova I, Bowman-Colin C, Chen G, Price S, Barnard N, Ganesan S, Karantza V, White E and Xia B. (2013) Autophagy opposes p53-mediated tumor barrier to facilitate tumorigenesis in a model of PALB2-associated hereditary breast cancer. Cancer Discov 3:894-907.
  • Ma J, Cai H, Wu T, Sobhian B, Huo Y, Mehta M, Cheung KL, Ganesan S, Kong T, Zhang DD and Xia B. (2012) PALB2 interacts with KEAP1 to promote NRF2 nuclear accumulation and function. Mol Cell Biol 32:1506-17.
  • Tischkowitz, M and Xia B. (2010) PALB2/FANCN-recombining cancer and Fanconi anemia. Cancer Res 70:7353-9.
  • 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 author)
  • Erkko H*, Xia B*, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A, Kallioniemi A, Pylkäs K, Karppinen S, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Kataja V, Soini Y, Drapkin RI, Livingston DM and Winqvist R. (2007) A recurrent mutation in PALB2 in Finnish cancer families. Nature 446:316-319. (*co-first author)
  • Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H and de Winter, JP. (2007) Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Nat Genet 39:165-167.
  • Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, and Livingston DM. (2006) Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell 22:719-729.