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Publications from the Center for DNA Damage and Repair (CDDR)

  • RAD51

    The CDDR has developed a RAD51 immunohistochemistry assay for RAD51. Tumor cells with proficient homologous recombination (HR) have RAD51 foci.

    James M. Cleary, Andrew J. Aguirre, Geoffrey I. Shapiro and Alan D'Andrea: Biomarker-Guided Development of DNA Repair Inhibitors; Mol Cell, 2020.

    Sarah J. Hill and Alan D. D'Andrea: Predictive Potential of Head and Neck Squamous Cell Carcinoma Organoids; Cancer Discovery, 2019.

    A.G. Waks, O. Cohen, B. Kochupurakkal, D. Kim, C.E. Dunn, J. Buendia Buendia, S. Wander, K. Helvie, M.R. Lloyd, L. Marini, M.E. Hughes, S.S. Freeman, S.P. Ivy, J. Geradts, S. Isakoff, P. LoRusso, V.A. Adalsteinsson, S.M. Tolaney, U. Matulonis, I.E. Krop, A.D. D'Andrea, E.P. Winder, N.U. Lin. G. I. Shapiro and N. Wagle: Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer; Annals of Oncology, 2020.

    CRISPR

    The CDDR performs CRISPR screens with new DNA Repair Inhibitors or Cell Cycle Inhibitors in order to identify predictive biomarkers in cancers. sgRNAs which confer sensitivity to these drugs identify genes with a synthetic lethal relationship with the drug.

    Mu-Yan Cai, Connor E. Dunn, Wenxu Chen, Bose S. Kochupurakkal, Huy Nguyen, Lisa A. Moreau, Geoffrey I. Shapiro, Kalindi Parmar, David Kozono and Alan D. D'Andrea: Cooperation of the ATM and Fanconi Anemia/BRCA Pathways in Double-Strand Break End Resection; Cell Reports, 2020.

    Feng Li, David Kozono, Peter Deraska, Timothy Branigan, Connor Dunn, Xiao-Feng Zheng, Kalindi Parmar, Huy Nguyen, James DeCaprio, Geoffrey I. Shapiro and Alan D. D'Andrea: CHK1 Inhibitor Block Phosphorylation of FAM122A and Promotes Replication Stress; Mol Cell, 2020.

    Kristen E. Mengwasser, Richard O. Adeyemi, Yumei Leng, Mei Yuk Choi, Connor Clairmont, Alan D'Andrea, Stephen J. Elledge: Genetic Screens Reveal FEN1 and APEX2 as BRCA2 Synthetic Lethal Targets; Mol Cell, 2018.

    Organoids

    The CDDR generates patient tumor-derived organoid cultures which can be used for biomarker analysis and for precision medicine. The organoids can be analyzed for their sensitivity to novel DNA Repair inhibitors and drug combinations.

    Sarah J. Hill, Brennan Decker, Emma A. Roberts, Neil S. Horowitz, Michael G. Muto, Michael J. Worley Jr, Colleen M. Feltmate, Marisa R. Nucci, Elizabeth M. Swisher, Huy Nguyen, Chunyu Yang, Ryuji Morizane, Bose S. Kochupurakkal, Khanh T. Do, Panagiotis A. Konstantinopoulos, Joyce F. Liu, Joseph V. Bonventre, Ursula A. Matulonis, Geoffrey I. Shapiro, Ross S. Berkowitz, Christopher P. Crum and Alan D. D'Andrea: Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids; Cancer Discovery, 2018.

    Sarah J. Hill and Alan D. D'Andrea: Predictive Potential of Head and Neck Squamous Cell Carcinoma Organoids; Cancer Discovery, 2019.

    Biomarkers for Drug Response

    The CDDR identifies new biomarkers and establishes immunohistochemistry assays to analyze tumor tissue taken from cancer patients before and after drug treatment.

    Anniina Farkkila, Alfredo Rodriguez, Jaana Oikkonen, Doga C. Gulhan, Huy Nguyen, Julieta Dominguez, Sandra Ramos, Caitlin E. Mills, Fernando Perez-Villatoro, Jean-Bernard Lazaro, Jia Zhou, Connor S. Clairmont, Lisa A. Moreau, Peter J. Park, Peter K. Sorger, Sampsa Hautaniemi, Sara Frias, Alan D. D’Andrea: Heterogeneity and clonal evolution of acquired PARP inhibitor resistance in TP53- and BRCA1-deficient cells; Cancer Research, 2021.

    Kalindi Parmar, Bose S. Kochupurakkal, Jena-Bernard Lazaro, Zhigang C. Wang, Sangeetha Palakurthi, Paul T. Kirschmeier, Chunyu Yang, Larissa A Sambel, Anniina Farkkila, Elizaveta Reznichenko, Hunter D. Reavis, Connor E. Dunn, Lee Zou, Khanh T. Do, Panagiotis A. Konstantinopoulos, Ursula A. Matulonis, Joyce F. Liu, Alan D. D'Andrea, and Geoffrey I Shapiro: The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition; Clin Cancer Res, 2019.

    Panagiotis A Konstantinopoulos, William T Barry, Michael Birrer, Shannon N Westin, Karen A Cadoo, Geoffrey I Shapiro, Erica L Mayer, Roisin E O’Cearbhaill, Robert L Coleman, Bose Kochupurakkal, Christin Whalen, Jennifer Curtis, Sarah Farooq, Weixiu Luo, Julia Eismann, Mary K Buss, Carol Aghajanian, Gordon B Mills, Sangeetha Palakurthi, Paul Kirschmeier, Joyce Liu, Lewis C Cantley, Scott H Kaufmann, Elizabeth M Swisher, Alan D D’Andrea, Eric Winer, Gerburg M Wulf, Ursula A Matulonis: Olaparib and a-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial; Lancet Oncology, 2019.

    Connor S. Clairmont, Prabha Sarangi, Karthikeyan Ponnienselvan, Lucas D. Galli, Isabelle Csete, Lisa Moreau, Guillaume Adelmant, Dipanjan Chowdhury, Jarrod A. Marto and Alan D. D'Andrea: TRIP13 Regulates DNA Repair Pathway Choice through REV7 Conformational Change; Nat Cell Biology, 2020.

    Panagiotis A. Konstantinopoulos, Steven Waggoner, Gregory A. Vidal, Monica Mita, John W. Moroney, Robert Holloway, Linda Van Le, Jasgit C. Sachdev, Eloise Chapman-Davis, Gerardo Colon-Otero, Richard T. Penson, Ursula A. Matulonis, Young Bae Kim, Kathleen N. Moore, Elizabeth M. Swisher, Anniina Färkkilä, Alan D'Andrea, Erica Stringer-Reasor, Jing Wang, Nathan Buerstatte, Sujata Arora, Julie R. Graham, Dmitri Bobilev, Bruce J. Dezube, and Pamela Munster: Single-Arm Phases 1 and 2 Trial of Niraparib in Combination with Pembrolizumab in Patients with Recurrent Platinum-Resistant Ovarian Carcinoma; JAMA Oncology, 2019.

    Joshi Niraj, Anniina Farkkila and Alan D. D'Andrea: The Fanconi Anemia Pathway in Cancer; Annual Rev Cancer Bio, 2019.

    Anne S. Rajkumar-Calkins, Raphael Szalat, Matija Dreze, Iman Khan, Zoe Frazier, Elizaveta Reznichenkov, Matthew R. Schnorenberg, Yi-Fang Tsai, Huy Nguyen, Bose Kochupurakkal, Alan D. D'Andrea, Geoffrey I. Shapiro, Jean-Bernard Lazaro and Kent W. Mouw: Functional profiling of nucleotide excision repair in breast cancer; DNA Repair, 2019.

    Michele Carbone, Sarah T. Arron, Bruce Beutler, Angela Bononi, Webster Cavenee, James E. Cleaver, Carlo M. Croce, Alan D'Andrea, William D. Foulkes, Giovanni Gaudino, Joanna L. Groden, Elizabeth P. Henske, Ian D. Hickson, Paul M. Hwang, Richard D. Kolodner, Tak W. Mak, David Malkin, Raymond J. Monnat, Jr., Flavia Novelli, Harvey I. Pass, John H. Petrini, Laura S. Schmidt and Haining Yang: Tumour predisposition and cancer syndromes as models to study gene-environment interactions; Nature Reviews Cancer, 2020.

    James M. Cleary, Andrew J. Aguirre, Geoffrey I. Shapiro and Alan D. D'Andrea: Biomarker-Guided Development of DNA Repair Inhibitors; Mol Cell, 2020.

    Anniina Farkkila, Doga C. Gulhan, Julia Casado, Connor A. Jacobson, Huy Nguyen, Bose Kochupurakkal, Zoltan Maliga, Clarence Yapp, Yu-An Chen, Denis Schapiro, Yinghui Zhou, Julie R. Graham, Bruce J. Dezube, Pamela Munster, Sandro Santagata, Elizabeth Garcia, Scott Rodig, Ana Lako, Dipanjan Chowdhury, Geoffrey I. Shapiro, Ursula A. Matulonis, Peter J. Park, Sampsa Hautaniemi, Peter K. Sorger, Elizabeth M. Swisher, Alan D. D'Andrea, and Panagiotis A. Konstantinopoulos: Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer; Nat Comm, 2020.

    Feng Li, David Kozono, Peter Deraska, Timothy Branigan, Connor Dunn, Xiao-Feng Zheng, Kalindi Parmar, Huy Nguyen, James DeCaprio, Geoffrey I Shapiro, Dipanjan Chowdhury, and Alan D. D'Andrea: CHK1 Inhibitor Block Phosphorylation of FAM122A and Promotes Replication Stress; Mol Cell, 2020.

    Nui Li, Jian Wang, Susan S. Wallace, Jing Chen, Jia Zhou and Alan D. D'Andrea: Cooperation of the NEIL2 and Fanconi anemia/BRCA pathways in interstrand crosslink repair; Nucleic Acids Research, 2020.

    Jeffrey Patterson-Fortin and Alan D. D'Andrea: Exploiting the Microhomology-Mediated End-Joining Pathway in Cancer Therapy; Cancer Res, 2020.

    Alfredo Rodriguez, Kaiyang Zhang, Anniina Farkkila, Jessica Filiatrault, Chunyu Yang, Martha Velazquez, Elissa Furutani, Devorah C. Goldman, Benilde Garcia de Teresa, Gilda Garza-Mayen, Kelsey McQueen, Larissa A. Sambel, Bertha Molina, Leda Torres, Marisol Gonzalez, Eduardo Vadillo, Rosana Pelayo, William H. Fleming, Markus Grompe, Akiko Shimamura, Sampsa Hautaniemi, Joel Greenberger, Sara Frias, Kalindi Parmar, and Alan D. D'Andrea: MYC Promotes Bone Marrow Stem Cell Dysfunction in Fanconi Anemia; Cell Stem Cell, 2020.

    Panagiotis A. Konstantinopoulos, Su-Chun Cheng, Andrea E. Wahner-Hendrickson, Richard T. Penson, Susan T. Schumer, L. Austin Doyle, Elizabeth K. Lee, Elise C. Kohn, Linda R. Duska, Marta A. Crispens, Alexander B. Olawaiye, Ira S. Winer, Lisa M. Barroilhet, Siqing Fu, Michael T. McHale, Russell J. Schilder, Anniina Farkkila, Dipanjan Chowdhury, Jennifer Curtis, Roxanne S. Quinn, Brittany Bowes, Alan D. D'Andrea, Geoffrey I Shapiro and Ursula A. Matulonis: Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label randomized, phase 2 trial; Lancet Oncology, 2020.

    Pre-clinical Testing

    The CDDR develops new drug targets and new classes of drugs for cancer therapy.

    Kah Suan Lim, Heng Li, Emma A. Roberts, Emily F. Gaudiano, Connor Clairmont, Larissa Alinia Sambel, Karthikeyan Ponnienselvan, Jessica C. Liu, Chunyu Yang, David Kozono, Kalindi Parmar, Timur Yusufzai, Ning Zheng, and Alan D. D'Andrea: USP1 Is Required for Replication Fork Protection in BRCA1-Deficient Tumors; Mol Cell, 2018.

    Jia Zhou, Camille Gelot, Constantia Pantelidou, Adam Li, Hatice Yucel, Rachel E. David, Anniina Farkkila, Bose Kochupurakkal, Aleem Syed, Geoffrey I. Shapiro, John A. Tainer, Brian S.J. Blagg, Raphael Ceccaldi, and Alan D. D'Andrea: Polymerase Theta Inhibition Kills Homologous Recombination Deficient Tumors; bioRxiv, 2020.

    Alfredo Rodriguez, Chunyu Yang, Elissa Furutani, Benilde Garcia de Teresa, Martha Velazquez, Jessica Filiatrault, Larissa A. Sambel, Tin Phan, Patricia Flores-Guzman, Silvia Sanchez, Angelica Monsivais Orozco, Hector Mayani, Ozge V. Bolukbasi, Anniina Farkkila, Michael Epperly, Joel Greenberger, Akiko Shimamura, Sara Frias, Markus Grompe, Kalindi Parmar, and Alan D. D'Andrea: Inhibition of TGFb1 and TGFb3 promotes hematopoiesis in Fanconi anemia; Exp Hemat, 2020.

    Biomarkers for Immunotherapy Response

    The CDDR identifies biomarkers suitable for predicting immunotherapy responses.

    Kent W/ Mouw, and Alan D. D'Andrea: DNA Repair Deficiency and Immunotherapy Response; J of Clinical Onc, 2018.

    Kent Mouw, Michael S. Goldberg, Panagiotis A. Konstantinopoulos, and Alan D. D'Andrea: DNA Damage and Repair Biomarkers of Immunotherapy Response; Cancer Dis, 2017.

    Computational Approaches

    The CDDR uses computational analysis of public and CDDR experimental databases to identify biomarkers in cancers and to assess cancer risk and survival.

    Mu-Yan Cai, Connor E. Dunn, Wenxu Chen, Bose S. Kochupurakkal, Huy Nguyen, Lisa A. Moreau, Geoffrey I. Shapiro, Kalindi Parmar, David Kozono and Alan D. D'Andrea: Cooperation of the ATM and Fanconi Anemia/BRCA Pathways in Double-Strand Break End Resection; Cell Reports, 2020.

    Feng Li, David Kozono, Peter Deraska, Timothy Branigan, Connor Dunn, Xiao-Feng Zheng, Kalindi Parmar, Huy Nguyen, James DeCaprio, Geoffrey I. Shapiro and Alan D. D'Andrea: CHK1 Inhibitor Block Phosphorylation of FAM122A and Promotes Replication Stress; Mol Cell, 2020.

    Paz Polak, Jaegil Kim, Lior Z. Braunstein, Rosa Karlic, Nicholas J. Haradhavala, Grace Tiao, Daniel Rosebrock, Dimitri Livitz, Kirsten Kubler, Kent W. Mouw, Atanas Kamburov, Yosef E. Maruvka, Ignaty, Leshchiner, Eric S. Lander, Todd R. Golub, Aviad Zick, Alexandre Orthwein, Michael S. Lawrence, Rajbir N. Batra, Carlos Caldas, Daniel A. Haber, Peter W. Laird, Hui Shen, Leif W. Ellisen, Alan D. D'Andrea, Stephen J. Chanock, William D. Foulkes and Gad Getz: A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer; Nat Genetics, 2017.

    Jaegil Kim, Kent W. Mouw, Paz Polak, Lior Z. Braunstein, Atanas Kamburov, Grace Tiao, David J. Kwiatkowski, Jonathan E. Rosenberg, Eliezer M. Van Allen, Alan D. D'Andrea and Gad Getz: Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors; Nat Genetics, 2016.