Junran Zhang, MD, PhD

Assistant Professor
Department of Radiation Oncology
School of Medicine
Co-Director
Department of Radiation Shared Resources
Case Comprehensive Cancer Center
School of Medicine
Member
Molecular Oncology Program
Case Comprehensive Cancer Center

Research Information

Research Projects

DNA double strand breaks (DSBs) are the most dangerous type of DNA lesion, because incorrectly repaired DSB can result in genomic instability, a major driving force in the onset and development of cancer. Cells that are deficient in DNA DSB repair are sensitive to ionizing radiation (IR) and chemotherapeutic drugs that cause DNA DSBs. Therefore, perturbations of DSB repair that promote carcinogenesis by causing genomic instability may also be the Achilles' heel of cancer. Understanding the molecular mechanisms that are involved in DNA DSB responses has become a central topic in cancer biology and radiation biology.

The goal of my research is to identify the molecular mechanisms maintaining genomic stability and to explore novel strategies targeting cancer cells by studying responses to DNA DSB formation.

‌Three major ongoing research projects in my group:

  • Delineate the role of RNF126 in DNA DSB response and its implications in cancer therapy.
  • Determine the mechanisms controlling homologous recombination-mediated repair in response to replication stress, especially at Common Fragile Sites (CFSs). CFSs are the genomic regions prone to form breaks during replication stress and are frequent targets of genomic alterations in both tumors and precancerous lesions.
  • Identify novel factors sensitizing cancer cells to ionizing radiation and to CHK1 inhibitors using Decode pooled lentiviral shRNA screening libraries.

Publications

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Bibliography (Selected from 48 publications)

Zhang, Y., Lai, J., Du, Z., Gao, J., Yang, S., Gorityala, S., Xiong, X., Deng, O., Ma, Z., Yan, C., Susana, G., Xu, Y. and Zhang, J. (2016) Targeting radioresistant breast cancer cells by single agent CHK1 inhibitor via enhancing replication stressOncotarget. 2016 Jun 7;7(23):34688-702. doi: 10.18632/oncotarget.9156.

Yang, H.Y., Barbi, J., Wu, C.Y., Zheng, Y., Vignali, P.D., Wu, X., Tao, J.H., Park, B.V., Bandara, S., Novack, L., Ni, X., Yang, X., Chang, K.Y., Wu, R.C., Zhang, J., Yang, C.W., Pardoll, D.M., Li, H. and Pan, F. (2016) MicroRNA-17 Modulates Regulatory T Cell Function by Targeting Co-regulators of the Foxp3 Transcription FactorImmunity. 2016 Jul 19;45(1):83-93. doi: 10.1016/j.immuni.2016.06.022.

Wang, Y., Deng, O., Feng, Z., Du, Z., Xiong, X., Lai, J., Yang, X., Xu, M., Wang, H., Taylor, D., Yan, C., Chen, C., Difeo, A., Ma, Z. and Zhang, J. (2016) RNF126 promotes homologous recombination via regulation of E2F1-mediated BRCA1 expressionOncogene. 2016 Mar 17;35(11):1363-72. doi: 10.1038/onc.2015.198. Epub 2015 Aug 3.

Hedrich, W.D., Xiao, J., Heyward, S., Zhang, Y., Zhang, J., Baer, M.R., Hassan, H.E. and Wang, H. (2016) Activation of the Constitutive Androstane Receptor Increases the Therapeutic Index of CHOP in Lymphoma TreatmentMol Cancer Ther. 2016 Mar;15(3):392-401. doi: 10.1158/1535-7163.MCT-15-0667. Epub 2016 Jan 28.

Graziano, S., Johnston, R., Deng, O., Zhang, J. and Gonzalo, S. (2016) Vitamin D/vitamin D receptor axis regulates DNA repair during oncogene-induced senescenceOncogene. 2016 Oct 13;35(41):5362-5376. doi: 10.1038/onc.2016.77. Epub 2016 Apr 4.

Cui, H., Li, X., Han, C., Wang, Q.E., Wang, H., Ding, H.F., Zhang, J. and Yan, C. (2016) The Stress-responsive Gene ATF3 Mediates Dichotomous UV Responses by Regulating the Tip60 and p53 ProteinsJ Biol Chem. 2016 May 13;291(20):10847-57. doi: 10.1074/jbc.M115.713099. Epub 2016 Mar 18.

Xiong, X., Du, Z., Wang, Y., Feng, Z., Fan, P., Yan, C., Willers, H. and Zhang, J. (2015) 53BP1 promotes microhomology-mediated end-joining in G1-phase cellsNucleic Acids Res. 2015 Feb 18;43(3):1659-70. doi: 10.1093/nar/gku1406. Epub 2015 Jan 13.

Wang, Z., Xu, D., Ding, H.F., Kim, J., Zhang, J., Hai, T. and Yan, C. (2015) Loss of ATF3 promotes Akt activation and prostate cancer development in a Pten knockout mouse modelOncogene34, 4975-4984.

Wang, Z., Kim, J., Teng, Y., Ding, H.F., Zhang, J., Hai, T., Cowell, J.K. and Yan, C. (2015) Loss of ATF3 promotes hormone-induced prostate carcinogenesis and the emergence of CK5CK8 epithelial cellsOncogene. 2016 Jul 7;35(27):3555-64. doi: 10.1038/onc.2015.417. Epub 2015 Nov 2.

Li, L., Li, H., Garzel, B., Yang, H., Sueyoshi, T., Li, Q., Shu, Y., Zhang, J., Hu, B., Heyward, S., Moeller, T., Xie, W., Negishi, M. and Wang, H. (2015) SLC13A5 is a novel transcriptional target of the pregnane X receptor and sensitizes drug-induced steatosis in human liverMol Pharmacol. 2015 Apr;87(4):674-82. doi: 10.1124/mol.114.097287. Epub 2015 Jan 27.

Krishnamurthy, N., Liu, L., Xiong, X., Zhang, J. and Montano, M.M. (2015) Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cellsCancer Biol Ther. 2015;16(4):518-27. doi: 10.1080/15384047.2015.1016661. Epub 2015 Apr 7.

Kan, C. and Zhang, J. (2015) BRCA1 Mutation: A Predictive Marker for Radiation Therapy? IInt J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):281-93. doi: 10.1016/j.ijrobp.2015.05.037. ASTRO issued a press release to highlight this manuscript to the national media

Cui, H., Guo, M., Xu, D., Ding, Z.C., Zhou, G., Ding, H.F., Zhang, J., Tang, Y. and Yan, C. (2015) The stress-responsive gene ATF3 regulates the histone acetyltransferase Tip60. Nat Commun. 2015 Apr 13;6:6752. doi: 10.1038/ncomms7752.

Chatterjee, P., Choudhary, G.S., Alswillah, T., Xiong, X., Heston, W.D., Magi-Galluzzi, C., Zhang, J., Klein, E.A. and Almasan, A. (2015) The TMPRSS2-ERG Gene Fusion Blocks XRCC4-Mediated Nonhomologous End-Joining Repair and Radiosensitizes Prostate Cancer Cells to PARP InhibitionMol Cancer Ther. 2015 Aug;14(8):1896-906. doi: 10.1158/1535-7163.MCT-14-0865. Epub 2015 May 29.

Brett-Morris, A., Wright, B.M., Seo, Y., Pasupuleti, V., Zhang, J., Lu, J., Spina, R., Bar, E.E., Gujrati, M., Schur, R., Lu, Z.R. and Welford, S.M. (2014) The polyamine catabolic enzyme SAT1 modulates tumorigenesis and radiation response in GBMCancer Res. 2014 Dec 1;74(23):6925-34. doi: 10.1158/0008-5472.CAN-14-1249. Epub 2014 Oct 2.

Zhang, J. (2013) The role of BRCA1 in homologous recombination repair in response to replication stress: significance in tumorigenesis and cancer therapyCell Biosci. 2013 Feb 6;3(1):11. doi: 10.1186/2045-3701-3-11. Most highly accessed article from that journal since its publication.

Li, Y., Chen, X., Wang, Z., Zhao, D., Chen, H., Chen, W., Zhou, Z., Zhang, J., Li, H. and Chen, C. (2013) The HECTD3 E3 ubiquitin ligase suppresses cisplatin-induced apoptosis via stabilizing MALT1Neoplasia15(1), 39-48.

Grotsky, D.A., Gonzalez-Suarez, I., Novell, A., Neumann, M.A., Yaddanapudi, S.C., Croke, M., Martinez-Alonso, M., Redwood, A.B., Ortega-Martinez, S., Feng, Z., Lerma, E., Ramon y Cajal, T., Zhang, J., Matias-Guiu, X., Dusso, A. and Gonzalo, S. (2013) BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cellsJ Cell Biol. 2013 Jan 21;200(2):187-202. doi: 10.1083/jcb.201204053.

Feng, Z. and Zhang, J. (2012) A dual role of BRCA1 in two distinct homologous recombination mediated repair in response to replication arrestNucleic Acids Res. 2012 Jan;40(2):726-38. doi: 10.1093/nar/gkr748. Epub 2011 Sep 27.

Redwood, A.B., Perkins, S.M., Vanderwaal, R.P., Feng, Z., Biehl, K.J., Gonzalez-Suarez, I., Morgado-Palacin, L., Shi, W., Sage, J., Roti-Roti, J.L., Stewart, C.L., Zhang, J. and Gonzalo, S. (2011) A dual role for A-type lamins in DNA double-strand break repairCell Cycle. 2011 Aug 1;10(15):2549-60. Epub 2011 Aug 1.

Helmink, B.A., Tubbs, A.T., Dorsett, Y., Bednarski, J.J., Walker, L.M., Feng, Z., Sharma, G.G., McKinnon, P.J., Zhang, J., Bassing, C.H. and Sleckman, B.P. (2011) H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytesNature. 2011 Jan 13;469(7329):245-9. doi: 10.1038/nature09585. Epub 2010 Dec 15.

Chen, H., Ma, Z., Vanderwaal, R.P., Feng, Z., Gonzalez-Suarez, I., Wang, S., Roti Roti, J.L. and Gonzalo, S and Zhang, J., (2011) The mTOR inhibitor rapamycin suppresses DNA double-strand break repairRadiat Res. 2011 Feb;175(2):214-24. Epub 2010 Oct 26.

Shi, W., Feng, Z., Gonzalez-Suarez, I., Vanderwaal, R.P., Wu, X., Powell, S.N., Roti Roti, J.L. and Gonzalo, S and Zhang, J., (2010) The role of RPA2 phosphorylation in homologous recombination in response to replication arrestCarcinogenesis. 2010 Jun;31(6):994-1002. doi: 10.1093/carcin/bgq035. Epub 2010 Feb 3.

Shi, W., Ma, Z., Willers, H., Akhtar, K., Scott, S.P., Powell, S and Zhang, J.  (2008) Disassembly of MDC1 foci is controlled by ubiquitin-proteasome-dependent degradationJ Biol Chem. 2008 Nov 14;283(46):31608-16. doi: 10.1074/jbc.M801082200. Epub 2008 Aug 29.

Treszezamsky, A.D., Kachnic, L.A., Feng, Z., Zhang, J., Tokadjian, C. and Powell, S.N. (2007) BRCA1- and BRCA2-deficient cells are sensitive to etoposide-induced DNA double-strand breaks via topoisomerase IICancer Res. 2007 Aug 1;67(15):7078-81.

Zhuang, J., Zhang, J., Willers, H., Wang, H., Chung, J.H., van Gent, D.C., Hallahan, D.E., Powell, S.N. and Xia, F. (2006) Checkpoint kinase 2-mediated phosphorylation of BRCA1 regulates the fidelity of nonhomologous end-joiningCancer Res. 2006 Feb 1;66(3):1401-8. (The first two authors contributed equally to this work).

Pandita, R.K., Sharma, G.G., Laszlo, A., Hopkins, K.M., Davey, S., Chakhparonian, M., Gupta, A., Wellinger, R.J., Zhang, J., Powell, S.N., Roti Roti, J.L., Lieberman, H.B. and Pandita, T.K. (2006) Mammalian Rad9 plays a role in telomere stability, S- and G2-phase-specific cell survival, and homologous recombinational repairMol Cell Biol. 2006 Mar;26(5):1850-64.

Ma, Z., Gibson, S.L., Byrne, M.A., Zhang, J., White, M.F. and Shaw, L.M. (2006) Suppression of insulin receptor substrate 1 (IRS-1) promotes mammary tumor metastasisMol Cell Biol. 2006 Dec;26(24):9338-51. Epub 2006 Oct 9.

Zhang, J. and Powell, S.N. (2005) The role of the BRCA1 tumor suppressor in DNA double-strand break repairMol Cancer Res. 2005 Oct;3(10):531-9.

Zhang, J., Ma, Z., Treszezamsky, A. and Powell, S.N. (2005) MDC1 interacts with Rad51 and facilitates homologous recombinationNat Struct Mol Biol. 2005 Oct;12(10):902-9. Epub 2005 Sep 25.

Litman, R., Peng, M., Jin, Z., Zhang, F., Zhang, J., Powell, S., Andreassen, P.R. and Cantor, S.B. (2005) BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJCancer Cell. 2005 Sep;8(3):255-65.

Zhang, J., Willers, H., Feng, Z., Ghosh, J.C., Kim, S., Weaver, D.T., Chung, J.H., Powell, S.N. and Xia, F. (2004) Chk2 phosphorylation of BRCA1 regulates DNA double-strand break repairMol Cell Biol. 2004 Jan;24(2):708-18.

Feng, Z., Kachnic, L., Zhang, J., Powell, S.N. and Xia, F. (2004) DNA damage induces p53-dependent BRCA1 nuclear export. J Biol Chem. 2004 Jul 2;279(27):28574-84. Epub 2004 Apr 15.

Ma, Z.F., Wang, Z.Y., Zhang, J.R., Gong, P. and Chen, H.L. (2001) Carcinogenic potential of duodenal reflux juice from patients with long-standing postgastrectomyWorld J Gastroenterol. 2001 Jun;7(3):376-80.