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Sharon B Cantor PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentMolecular, Cell and Cancer Biology
AddressUniversity of Massachusetts Medical School
364 Plantation Street, LRB
Worcester MA 01605
Phone508-856-4421
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentMolecular, Cell and Cancer Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentCancer Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program


    Collapse Biography 
    Collapse education and training
    University of Michigan, Ann Arbor, Ann Arbor, MI, United StatesBSBiology
    Sackler School of Graduate Biomedical Sciences, Boston, MA, United StatesPHDBiochemistry

    Collapse Overview 
    Collapse overview


    See Cantor Lab Website



    Hereditary Breast Cancer



    Photo: Sharon Cantor



    Research in our group is focused on understanding how cells normally function to maintain genomic integrity and suppress cancer. In particular, we focus on the hereditary breast and ovarian cancer genes, BRCA1, BRCA2 and FANCJ (also known as BACH1 or BRIP1). FANCJ was named the BRCA1 Associated C-terminal Helicase (BACH1) because of its direct interaction with the C-terminal BRCA1-BRCT repeats and its ability to unwind the strands of DNA in an energy-dependent reaction. Human genetic studies resulted in the identification of two early-onset breast cancer patients with germ-line sequence changes in the FANCJ coding region. When these sequence changes were studied in vitro, both mutations resulted in a defective FANCJ protein. Interestingly, the (P47A) mutant disrupted and the (M299I) mutant enhanced the enzyme activity implicating that too little or too much enzyme activity predisposes to disease.



    Similar to BRCA2, FANCJ is also mutated in the cancer prone syndrome, Fanconi anemia (FA). FA is a chromosomal instability syndrome characterized by cellular hypersensitivity to DNA crosslinking agents, such as cisplatin. FA is a multi-genetic disease with at least 13 complementation groups identified and referred to as FA-A through FA-N. BRCA2 is the FANCD1 gene mutated in the FA-D1 complementation group whereas FANCJ is mutated in the FA-J complementation group. So far, FA associated mutations in FANCJ appear to be enzyme inactivating or disrupt FANCJ expression.



    Research indicates that proteins functioning in the so-called, FA-BRCA pathway suppress cancer because of roles in preserving the integrity of the genome. The FA-BRCA proteins function to repair DNA lesions, such as DNA inter-strand crosslinks through several activities including the promotion of homologous recombination (HR). HR is a relatively error-free mechanism to repair DNA double strand breaks. In addition, the FA-BRCA pathway has roles in promoting DNA damage tolerance through translesion synthesis, a typically error-prone mechanism. By functioning together in large complexes, the FA-BRCA proteins can reverse toxic DNA crosslinks with minimal error generation and restart replication forks.



    The laboratory is interested in a range of repair-related topics including (i) the role of FANCJ in DNA repair, DNA damage tolerance, and checkpoint signaling and how these functions contribute to tumor suppression (ii) how FANCJ function is regulated by direct interactions with BRCA1 and MLH1, a mismatch repair protein, (iii) the relationship between FANCJ, BRCA1, and MLH1 in DNA crosslink repair, (iv) identifying novel FANCJ protein modifications or interacting partners that contribute to the function of FANCJ in the DNA damage response and (v) understanding the underlying defects associated with loss of function of proteins in the BRCA-FA pathway and whether these defects can be suppressed.



    The long-term objective of our research is to use our basic understanding of the FA-BRCA pathway to identify clinical applications in the treatment of FA-BRCA associated cancers or syndromes.



    Collapse Rotation Projects



    Rotation projects are available to study the role of the BACH1/FANCJ DNA helicase in the DNA damage response and tumor suppression.  We have uncovered that FANCJ contributes to both error-free and error-prone DNA damage response pathways.   Error-prone pathways are essential for cells to survive certain forms of DNA damage.  However, when not properly regulated error-prone pathways contribute to genomic instability, cancer, and chemoresistance. Our data indicate that dysregulation of error-prone pathways is a consequence of FANCJ breast cancer mutations.  Moreover, we identified DNA damage induced post-translational modifications that regulate FANCJ function and its contribution to DNA damage pathway choice. Rotation projects include dissecting whether FANCJ clinical mutations interfere with FANCJ post-translational modifcations.  Do FANCJ clinical mutants exclusively promote error-prone lesion processing? In addition, we are interested in elucidating the mechanism by which FANCJ contributes to DNA repair pathway choice.  In particular, FANCJ could contribute to repair choice using its DNA helicase/ translocase activity. The goal will be to analyze whether FANCJ unwinds DNA substrates and/or displacing proteins, to enhance DNA lesion processing by a distinct set of repair factors. 



    Collapse Post Docs

    A post-doctoral position is available immediately to study the role of genes found in a genome-wide RNAi screen to regulate the cellular response to the chemotherapy agent, cisplatin. The goal is to determine whether these genes function as tumor suppressor and/or regulate the mechanism of DNA repair processing.  The laboratory is interested in understanding the role of hereditary cancer genes of the BRCA-Fanconi anemia pathway in DNA damage repair and tumor suppression.  We seek motivated candidates with a PhD and background in cancer cell biology.  Experience in mouse cancer models is desirable. The exceptional training environment within the Department of Cancer Biology at UMASS Medical School offers a rigorous and interactive research environment covering several aspects of tumor biology.  Applicants should have excellent communication skills, and ability to conduct research independently and as a team. To apply, please send your CV with bibliography, a brief description of research experience and contact information for at least two references via email. 




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Paes Dias M, Tripathi V, van der Heijden I, Cong K, Manolika EM, Bhin J, Gogola E, Galanos P, Annunziato S, Lieftink C, Andújar-Sánchez M, Chakrabarty S, Smith GCM, van de Ven M, Beijersbergen RL, Bartkova J, Rottenberg S, Cantor S, Bartek J, Ray Chaudhuri A, Jonkers J. Loss of nuclear DNA ligase III reverts PARP inhibitor resistance in BRCA1/53BP1 double-deficient cells by exposing ssDNA gaps. Mol Cell. 2021 Sep 18. PMID: 34555355.
      View in: PubMed
    2. Cantor SB. Revisiting the BRCA-pathway through the lens of replication gap suppression: "Gaps determine therapy response in BRCA mutant cancer". DNA Repair (Amst). 2021 Aug 13; 107:103209. PMID: 34419699.
      View in: PubMed
    3. Cong K, Peng M, Kousholt AN, Lee WTC, Lee S, Nayak S, Krais J, VanderVere-Carozza PS, Pawelczak KS, Calvo J, Panzarino NJ, Turchi JJ, Johnson N, Jonkers J, Rothenberg E, Cantor SB. Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency. Mol Cell. 2021 Aug 05; 81(15):3227. PMID: 34358459.
      View in: PubMed
    4. Cong K, Peng M, Kousholt AN, Lee WTC, Lee S, Nayak S, Krais J, VanderVere-Carozza PS, Pawelczak KS, Calvo J, Panzarino NJ, Jonkers J, Johnson N, Turchi JJ, Rothenberg E, Cantor SB. Replication gaps are a key determinant of PARP inhibitor synthetic lethality with BRCA deficiency. Mol Cell. 2021 Jun 26. PMID: 34216544.
      View in: PubMed
    5. Lee WTC, Yin Y, Morten MJ, Tonzi P, Gwo PP, Odermatt DC, Modesti M, Cantor SB, Gari K, Huang TT, Rothenberg E. Single-molecule imaging reveals replication fork coupled formation of G-quadruplex structures hinders local replication stress signaling. Nat Commun. 2021 05 05; 12(1):2525. PMID: 33953191.
      View in: PubMed
    6. Calvo JA, Fritchman B, Hernandez D, Persky NS, Johannessen CM, Piccioni F, Kelch BA, Cantor SB. Comprehensive Mutational Analysis of the BRCA1-Associated DNA Helicase and Tumor-Suppressor FANCJ/BACH1/BRIP1. Mol Cancer Res. 2021 Feb 22. PMID: 33619228.
      View in: PubMed
    7. Nayak S, Calvo JA, Cantor SB. Targeting translesion synthesis (TLS) to expose replication gaps, a unique cancer vulnerability. Expert Opin Ther Targets. 2021 Jan 08; 1-10. PMID: 33416413.
      View in: PubMed
    8. Panzarino NJ, Krais JJ, Cong K, Peng M, Mosqueda M, Nayak SU, Bond SM, Calvo JA, Doshi MB, Bere M, Ou J, Deng B, Zhu LJ, Johnson N, Cantor SB. Replication Gaps Underlie BRCA-deficiency and Therapy Response. Cancer Res. 2020 Nov 12. PMID: 33184108.
      View in: PubMed
    9. Awate S, Sommers JA, Datta A, Nayak S, Bellani MA, Yang O, Dunn CA, Nicolae CM, Moldovan GL, Seidman MM, Cantor SB, Brosh RM. FANCJ compensates for RAP80 deficiency and suppresses genomic instability induced by interstrand cross-links. Nucleic Acids Res. 2020 Aug 14. PMID: 32797166.
      View in: PubMed
    10. Nayak S, Calvo JA, Cong K, Peng M, Berthiaume E, Jackson J, Zaino AM, Vindigni A, Hadden MK, Cantor SB. Inhibition of the translesion synthesis polymerase REV1 exploits replication gaps as a cancer vulnerability. Sci Adv. 2020 Jun; 6(24):eaaz7808. PMID: 32577513.
      View in: PubMed
    11. Cantor S. TPX2 joins 53BP1 to maintain DNA repair and fork stability. J Cell Biol. 2019 Jan 11. PMID: 30635354.
      View in: PubMed
    12. Peng M, Cong K, Panzarino NJ, Nayak S, Calvo J, Deng B, Zhu LJ, Morocz M, Hegedus L, Haracska L, Cantor SB. Opposing Roles of FANCJ and HLTF Protect Forks and Restrain Replication during Stress. Cell Rep. 2018 Sep 18; 24(12):3251-3261. PMID: 30232006.
      View in: PubMed
    13. Cantor SB, Calvo JA. Fork Protection and Therapy Resistance in Hereditary Breast Cancer. Cold Spring Harb Symp Quant Biol. 2018 Feb 22. PMID: 29472318.
      View in: PubMed
    14. Suzuki S, Racine RR, Manalo NA, Cantor SB, Raffel GD. Impairment of fetal hematopoietic stem cell function in the absence of Fancd2. Exp Hematol. 2016 Dec 01. PMID: 27915139.
      View in: PubMed
    15. Chaudhuri AR, Callen E, Ding X, Gogola E, Duarte AA, Lee JE, Wong N, Lafarga V, Calvo JA, Panzarino NJ, John S, Day A, Crespo AV, Shen B, Starnes LM, de Ruiter JR, Daniel JA, Konstantinopoulos PA, Cortez D, Cantor SB, Fernandez-Capetillo O, Ge K, Jonkers J, Rottenberg S, Sharan SK, Nussenzweig A. Erratum: Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature. 2016 Nov 17; 539(7629):456. PMID: 27680696.
      View in: PubMed
    16. Ray Chaudhuri A, Callen E, Ding X, Gogola E, Duarte AA, Lee JE, Wong N, Lafarga V, Calvo JA, Panzarino NJ, John S, Day A, Crespo AV, Shen B, Starnes LM, de Ruiter JR, Daniel JA, Konstantinopoulos PA, Cortez D, Cantor SB, Fernandez-Capetillo O, Ge K, Jonkers J, Rottenberg S, Sharan SK, Nussenzweig A. Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature. 2016 07 21; 535(7612):382-7. PMID: 27443740.
      View in: PubMed
    17. Cantor SB, Nayak S. FANCJ at the FORK. Mutat Res. 2016 Jun; 788:7-11. PMID: 26926912.
      View in: PubMed
    18. Guillemette S, Serra RW, Peng M, Hayes JA, Konstantinopoulos PA, Green MR, Cantor SB. Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4. Genes Dev. 2015 Mar 1; 29(5):489-94. PMID: 25737278.
      View in: PubMed
    19. Brosh RM, Cantor SB. Molecular and cellular functions of the FANCJ DNA helicase defective in cancer and in Fanconi anemia. Front Genet. 2014; 5:372. PMID: 25374583.
      View in: PubMed
    20. Peng M, Xie J, Ucher A, Stavnezer J, Cantor SB. Crosstalk between BRCA-Fanconi anemia and mismatch repair pathways prevents MSH2-dependent aberrant DNA damage responses. EMBO J. 2014 Aug 1; 33(15):1698-712. PMID: 24966277.
      View in: PubMed
    21. Cantor SB, Brosh RM. What is wrong with Fanconi anemia cells? Cell Cycle. 2014; 13(24):3823-7. PMID: 25486020.
      View in: PubMed
    22. Guillemette S, Branagan A, Peng M, Dhruva A, Schärer OD, Cantor SB. FANCJ localization by mismatch repair is vital to maintain genomic integrity after UV irradiation. Cancer Res. 2014 Feb 1; 74(3):932-44. PMID: 24351291.
      View in: PubMed
    23. Suhasini AN, Sommers JA, Muniandy PA, Coulombe Y, Cantor SB, Masson JY, Seidman MM, Brosh RM. Fanconi anemia group J helicase and MRE11 nuclease interact to facilitate the DNA damage response. Mol Cell Biol. 2013 Jun; 33(11):2212-27. PMID: 23530059.
      View in: PubMed
    24. Xie J, Peng M, Guillemette S, Quan S, Maniatis S, Wu Y, Venkatesh A, Shaffer SA, Brosh RM, Cantor SB. FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage response. PLoS Genet. 2012 Jul; 8(7):e1002786. PMID: 22792074.
      View in: PubMed
    25. Cantor SB, Guillemette S. Hereditary breast cancer and the BRCA1-associated FANCJ/BACH1/BRIP1. Future Oncol. 2011 Feb; 7(2):253-61. PMID: 21345144.
      View in: PubMed
    26. Suhasini AN, Rawtani NA, Wu Y, Sommers JA, Sharma S, Mosedale G, North PS, Cantor SB, Hickson ID, Brosh RM. Interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome. EMBO J. 2011 Feb 16; 30(4):692-705. PMID: 21240188.
      View in: PubMed
    27. Xie J, Guillemette S, Peng M, Gilbert C, Buermeyer A, Cantor SB. An MLH1 mutation links BACH1/FANCJ to colon cancer, signaling, and insight toward directed therapy. Cancer Prev Res (Phila). 2010 Nov; 3(11):1409-16. PMID: 20978114.
      View in: PubMed
    28. Cantor SB, Xie J. Assessing the link between BACH1/FANCJ and MLH1 in DNA crosslink repair. Environ Mol Mutagen. 2010 Jul; 51(6):500-7. PMID: 20658644.
      View in: PubMed
    29. Xie J, Litman R, Wang S, Peng M, Guillemette S, Rooney T, Cantor SB. Targeting the FANCJ-BRCA1 interaction promotes a switch from recombination to poleta-dependent bypass. Oncogene. 2010 Apr 29; 29(17):2499-508. PMID: 20173781.
      View in: PubMed
    30. Sommers JA, Rawtani N, Gupta R, Bugreev DV, Mazin AV, Cantor SB, Brosh RM. FANCJ uses its motor ATPase to destabilize protein-DNA complexes, unwind triplexes, and inhibit RAD51 strand exchange. J Biol Chem. 2009 Mar 20; 284(12):7505-17. PMID: 19150983.
      View in: PubMed
    31. Siehler SY, Schrauder M, Gerischer U, Cantor S, Marra G, Wiesmüller L. Human MutL-complexes monitor homologous recombination independently of mismatch repair. DNA Repair (Amst). 2009 Feb 1; 8(2):242-52. PMID: 19022408.
      View in: PubMed
    32. Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O'Neil NJ, Petalcorin MI, Martin JS, Collis SJ, Cantor SB, Auclair M, Tissenbaum H, West SC, Rose AM, Boulton SJ. RTEL1 maintains genomic stability by suppressing homologous recombination. Cell. 2008 Oct 17; 135(2):261-71. PMID: 18957201.
      View in: PubMed
    33. Litman R, Gupta R, Brosh RM, Cantor SB. BRCA-FA pathway as a target for anti-tumor drugs. Anticancer Agents Med Chem. 2008 May; 8(4):426-30. PMID: 18473727.
      View in: PubMed
    34. Gupta R, Sharma S, Sommers JA, Kenny MK, Cantor SB, Brosh RM. FANCJ (BACH1) helicase forms DNA damage inducible foci with replication protein A and interacts physically and functionally with the single-stranded DNA-binding protein. Blood. 2007 Oct 1; 110(7):2390-8. PMID: 17596542.
      View in: PubMed
    35. Peng M, Litman R, Xie J, Sharma S, Brosh RM, Cantor SB. The FANCJ/MutLalpha interaction is required for correction of the cross-link response in FA-J cells. EMBO J. 2007 Jul 11; 26(13):3238-49. PMID: 17581638.
      View in: PubMed
    36. Gupta R, Sharma S, Doherty KM, Sommers JA, Cantor SB, Brosh RM. Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand. Nucleic Acids Res. 2006; 34(22):6673-83. PMID: 17145708.
      View in: PubMed
    37. Peng M, Litman R, Jin Z, Fong G, Cantor SB. BACH1 is a DNA repair protein supporting BRCA1 damage response. Oncogene. 2006 Apr 6; 25(15):2245-53. PMID: 16462773.
      View in: PubMed
    38. Cantor SB, Andreassen PR. Assessing the link between BACH1 and BRCA1 in the FA pathway. Cell Cycle. 2006 Jan; 5(2):164-7. PMID: 16357529.
      View in: PubMed
    39. Greenberg RA, Sobhian B, Pathania S, Cantor SB, Nakatani Y, Livingston DM. Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes. Genes Dev. 2006 Jan 1; 20(1):34-46. PMID: 16391231.
      View in: PubMed
    40. Litman R, Peng M, Jin Z, Zhang F, Zhang J, Powell S, Andreassen PR, Cantor SB. BACH1 is critical for homologous recombination and appears to be the Fanconi anemia gene product FANCJ. Cancer Cell. 2005 Sep; 8(3):255-65. PMID: 16153896.
      View in: PubMed
    41. Gupta R, Sharma S, Sommers JA, Jin Z, Cantor SB, Brosh RM. Analysis of the DNA substrate specificity of the human BACH1 helicase associated with breast cancer. J Biol Chem. 2005 Jul 8; 280(27):25450-60. PMID: 15878853.
      View in: PubMed
    42. Cantor S, Drapkin R, Zhang F, Lin Y, Han J, Pamidi S, Livingston DM. The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations. Proc Natl Acad Sci U S A. 2004 Feb 24; 101(8):2357-62. PMID: 14983014.
      View in: PubMed
    43. Joo WS, Jeffrey PD, Cantor SB, Finnin MS, Livingston DM, Pavletich NP. Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure. Genes Dev. 2002 Mar 1; 16(5):583-93. PMID: 11877378.
      View in: PubMed
    44. Esnaola NF, Cantor SB, Sherman SI, Lee JE, Evans DB. Optimal treatment strategy in patients with papillary thyroid cancer: a decision analysis. Surgery. 2001 Dec; 130(6):921-30. PMID: 11742318.
      View in: PubMed
    45. Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, Wahrer DC, Sgroi DC, Lane WS, Haber DA, Livingston DM. BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function. Cell. 2001 Apr 6; 105(1):149-60. PMID: 11301010.
      View in: PubMed
    46. Chen JJ, Silver D, Cantor S, Livingston DM, Scully R. BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. Cancer Res. 1999 Apr 1; 59(7 Suppl):1752s-1756s. PMID: 10197592.
      View in: PubMed
    47. Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R. Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Mol Cell. 1998 Sep; 2(3):317-28. PMID: 9774970.
      View in: PubMed
    48. Feig LA, Urano T, Cantor S. Evidence for a Ras/Ral signaling cascade. Trends Biochem Sci. 1996 Nov; 21(11):438-41. PMID: 8987400.
      View in: PubMed
    49. Cantor SB, Urano T, Feig LA. Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases. Mol Cell Biol. 1995 Aug; 15(8):4578-84. PMID: 7623849.
      View in: PubMed
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