In the Laboratory of Genomic stability and Cancer Therapeutics we use a combination of biochemical and cell biological approaches to study the function of mammalian telomeres. Telomeres cap the ends of linear chromosomes and provide a molecular barrier for the human genome. Following each cell division, progressive telomere shortening erodes that barrier and compromises the stability of the genome. Critically short, or dysfunctional telomeres induce replicative senescence and/or cell death and ultimately, lead to cellular aging. Cancer cells, however, overcome the replicative senescence associated with critically short telomeres by exploiting mechanisms of telomere elongation. The focus of my lab is to understand the mechanisms regulating mammalian telomere maintenance and to understand how defects in this process contribute to premature aging and cancer progression. The hope is that these studies will allow us to gain the mechanistic insight necessary to define novel targets and/or strategies in the treatment of human disease.
- Assistant Professor, Hematology & Medical Oncology, Medicine, Boston University School of Medicine
- Peter Paul Career Development Professorship, Boston University
- University of Massachusetts Medical School, PhD
- Saint Michaels College-Vt, BS
- Published on 1/28/2016
Cox KE, Maréchal A, Flynn RL. SMARCAL1 Resolves Replication Stress at ALT Telomeres. Cell Rep. 2016 Feb 9; 14(5):1032-40. PMID: 26832416.
- Published on 1/16/2015
Flynn RL, Cox KE, Jeitany M, Wakimoto H, Bryll AR, Ganem NJ, Bersani F, Pineda JR, Suvà ML, Benes CH, Haber DA, Boussin FD, Zou L. Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Science. 2015 Jan 16; 347(6219):273-7. PMID: 25593184.
- Published on 2/15/2012
Flynn RL, Chang S, Zou L. RPA and POT1: friends or foes at telomeres? Cell Cycle. 2012 Feb 15; 11(4):652-7. PMID: 22373525.
- Published on 3/13/2011
Flynn RL, Centore RC, O'Sullivan RJ, Rai R, Tse A, Songyang Z, Chang S, Karlseder J, Zou L. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature. 2011 Mar 24; 471(7339):532-6. PMID: 21399625.
- Published on 10/12/2010
Flynn RL, Zou L. ATR: a master conductor of cellular responses to DNA replication stress. Trends Biochem Sci. 2011 Mar; 36(3):133-40. PMID: 20947357.
- Published on 10/8/2010
Centore RC, Havens CG, Manning AL, Li JM, Flynn RL, Tse A, Jin J, Dyson NJ, Walter JC, Zou L. CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase. Mol Cell. 2010 Oct 8; 40(1):22-33. PMID: 20932472.
- Published on 8/1/2010
Flynn RL, Zou L. Oligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians. Crit Rev Biochem Mol Biol. 2010 Aug; 45(4):266-75. PMID: 20515430.
- Published on 2/22/2010
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.
- Published on 1/1/2008
Litman R, Gupta R, Brosh RM Jr, Cantor SB. BRCA-FA pathway as a target for anti-tumor drugs. Anticancer Agents Med Chem. 2008; 8(4):426-30.
- Published on 6/21/2007
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.
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