Anindya Dutta

Education

  • MBBS, Christian Medical College, Vellore, India
  • PhD, The Rockefeller University, New York, NY
  • Postdoc, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY
  • Resident, Brigham and Women’s Hospital, Boston, MA

Primary Appointment

  • Professor and Chair, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

Genomic Instability in Cancer Cells; Noncoding RNAs in differentiation and cancer

Research Description

Our lab studies two different areas: genomic stability/instability in normal and cancer cells and the role of short and long noncoding RNAs in cell proliferation and differentiation. The projects in the lab are summarized below: (1) DNA replication and response to DNA damage in human cells to determine how disorders in their regulation lead to genomic instability. For example, we have mapped hundreds of origins of replication in human cells, study how anti-cancer drugs impact on their activity and discover novel targets for ubiquitination important for genomic stability. We have discovered novel extrachromosomal circles of DNA, microDNAs, in normal cells and tissues and are analyzing how they contribute to cell function. (2) MicroRNAs, novel non-micro short RNAs and long noncoding RNAs that regulate differentiation (muscle) or cancer progression (prostate). We discover RNAs that change during specific cellular transitions by cloning/high-throughput sequencing, determine whether the RNA is important for the biological transition and ascertain the mechanism of action of the RNA. We have discovered microRNAs and long noncoding RNAs critical for muscle differentiation and a new class of non-micro-short RNAs, tRFs , whose function is being investigated.

Selected Publications

  • Abbas T, Keaton M, Dutta A. Genomic instability in cancer. Cold Spring Harbor perspectives in biology. 2013;5(3): a012914. PMID: 23335075 | PMCID: PMC3578360
  • Abbas T, Keaton M, Dutta A. Regulation of TGF-β signaling, exit from the cell cycle, and cellular migration through cullin cross-regulation: SCF-FBXO11 turns off CRL4-Cdt2. Cell cycle (Georgetown, Tex.). 2013;12(14): 2175-82. PMID: 23892434 | PMCID: PMC3755067
  • Abbas T, Mueller A, Shibata E, Keaton M, Rossi M, Dutta A. CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration. Molecular cell. 2013;49(6): 1147-58. PMID: 23478445 | PMCID: PMC3615078
  • Dar A, Shibata E, Dutta A. Deubiquitination of Tip60 by USP7 determines the activity of the p53-dependent apoptotic pathway. Molecular and cellular biology. 2013;33(16): 3309-20. PMID: 23775119
  • Im J, Lee K, Dillon L, Dutta A. Human Primpol1: a novel guardian of stalled replication forks. EMBO reports. 2013;14(12): 1032-3. PMID: 24189099
  • Jazaeri A, Shibata E, Park J, Bryant J, Conaway M, Modesitt S, Smith P, Milhollen M, Berger A, Dutta A. Overcoming platinum resistance in preclinical models of ovarian cancer using the neddylation inhibitor MLN4924. Molecular cancer therapeutics. 2013;12(10): 1958-67. PMID: 23939375
  • Jha S, Gupta A, Dar A, Dutta A. RVBs are required for assembling a functional TIP60 complex. Molecular and cellular biology. 2013;33(6): 1164-74. PMID: 23297341
  • Park J, Long D, Lee K, Abbas T, Shibata E, Negishi M, Luo Y, Schimenti J, Gambus A, Walter J, Dutta A. The MCM8-MCM9 complex promotes RAD51 recruitment at DNA damage sites to facilitate homologous recombination. Molecular and cellular biology. 2013;33(8): 1632-44. PMID: 23401855 | PMCID: PMC3624244
  • Sun D, Layer R, Mueller A, Cichewicz M, Negishi M, Paschal B, Dutta A. Regulation of several androgen-induced genes through the repression of the miR-99a/let-7c/miR-125b-2 miRNA cluster in prostate cancer cells. Oncogene. 2013. PMID: 23503464
  • Terai K, Shibata E, Abbas T, Dutta A. Degradation of p12 Subunit by CRL4Cdt2 E3 Ligase Inhibits Fork Progression after DNA Damage. The Journal of biological chemistry. 2013;288(42): 30509-14. PMID: 24022480 | PMCID: PMC3798521
  • Dey B, Gagan J, Yan Z, Dutta A. miR-26a is required for skeletal muscle differentiation and regeneration in mice. Genes & development. 2012;26(19): 2180-91. PMID: 23028144
  • Dey B, Mueller A, Dutta A. Non-micro-short RNAs: the new kids on the block. Molecular biology of the cell. 2012;23(24): 4664-7. PMID: 23239791
  • Gagan J, Dey B, Dutta A. MicroRNAs regulate and provide robustness to the myogenic transcriptional network. Current opinion in pharmacology. 2012;12(3): 383-8. PMID: 22386695 | PMCID: PMC3369106
  • Gagan J, Dey B, Layer R, Yan Z, Dutta A. Notch3 and Mef2c Are Mutually Antagonistic via Mkp1 and miR-1/206 in Differentiating Myoblasts. The Journal of biological chemistry. 2012. PMID: 23055528
  • Gupta A, Jha S, Engel D, Ornelles D, Dutta A. Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator EIA. Oncogene. 2012. PMID: 23178490
  • Mueller A, Sun D, Dutta A. The miR-99 family regulates the DNA damage response through its target SNF2H. Oncogene. 2012. PMID: 22525276 | PMCID: PMC3407337
  • Shibata Y, Kumar P, Layer R, Willcox S, Gagan J, Griffith J, Dutta A. Extrachromosomal microDNAs and chromosomal microdeletions in normal tissues. Science (New York, N.Y.). 2012;336(6077): 82-6. PMID: 22403181
  • Abbas T, Dutta A. CRL4Cdt2: master coordinator of cell cycle progression and genome stability. Cell cycle (Georgetown, Tex.). 2011;10(2): 241-9. PMID: 21212733 | PMCID: PMC3025761
  • Gagan J, Dey B, Layer R, Yan Z, Dutta A. MicroRNA-378 targets the myogenic repressor MyoR during myoblast differentiation. The Journal of biological chemistry. 2011;286(22): 19431-8. PMID: 21471220 | PMCID: PMC3103322
  • Jazaeri A, Bryant J, Park H, Li H, Dahiya N, Stoler M, Ferriss J, Dutta A. Molecular requirements for transformation of fallopian tube epithelial cells into serous carcinoma. Neoplasia (New York, N.Y.). 2011;13(10): 899-911. PMID: 22028616 | PMCID: PMC3201567
  • Karnani N, Dutta A. The effect of the intra-S-phase checkpoint on origins of replication in human cells. Genes & development. 2011;25(6): 621-33. PMID: 21406556 | PMCID: PMC3059835
  • Keaton M, Dutta A. Rad18 emerges as a critical regulator of the Fanconi anemia pathway. Cell cycle (Georgetown, Tex.). 2011;10(15): 2414-5. PMID: 21795845 | PMCID: PMC3233489
  • Keaton M, Taylor C, Layer R, Dutta A. Nuclear scaffold attachment sites within ENCODE regions associate with actively transcribed genes. PloS one. 2011;6(3): e17912. PMID: 21423757 | PMCID: PMC3056778
  • Mueller A, Keaton M, Dutta A. DNA replication: mammalian Treslin-TopBP1 interaction mirrors yeast Sld3-Dpb11. Current biology : CB. 2011;21(16): R638-40. PMID: 21855008 | PMCID: PMC3523092
  • Zhang Y, Dutta A, Abounader R. The role of microRNAs in glioma initiation and progression. Frontiers in bioscience : a journal and virtual library. 2011;17 700-12. PMID: 22201769 | PMCID: PMC3278211
  • Abbas T, Shibata E, Park J, Jha S, Karnani N, Dutta A. CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation. Molecular cell. 2010;40(1): 9-21. PMID: 20932471 | PMCID: PMC2966975
  • Dey B, Gagan J, Dutta A. miR-206 and -486 induce myoblast differentiation by downregulating Pax7. Molecular and cellular biology. 2010;31(1): 203-14. PMID: 21041476 | PMCID: PMC3019853
  • Jazaeri A, Ferriss J, Bryant J, Dalton M, Dutta A. Evaluation of EVI1 and EVI1s (Delta324) as potential therapeutic targets in ovarian cancer. Gynecologic oncology. 2010;118(2): 189-95. PMID: 20462630
  • Jha S, Vande Pol S, Banerjee N, Dutta A, Chow L, Dutta A. Destabilization of TIP60 by human papillomavirus E6 results in attenuation of TIP60-dependent transcriptional regulation and apoptotic pathway. Molecular cell. 2010;38(5): 700-11. PMID: 20542002 | PMCID: PMC2886028
  • Lin J, Milhollen M, Smith P, Narayanan U, Dutta A. NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells. Cancer research. 2010;70(24): 10310-20. PMID: 21159650 | PMCID: PMC3059213
  • Sarkar S, Dey B, Dutta A. MiR-322/424 and -503 are induced during muscle differentiation and promote cell cycle quiescence and differentiation by down-regulation of Cdc25A. Molecular biology of the cell. 2010;21(13): 2138-49. PMID: 20462953 | PMCID: PMC2893979
  • Shibata Y, Malhotra A, Dutta A. Detection of DNA fusion junctions for BCR-ABL translocations by Anchored ChromPET. Genome medicine. 2010;2(9): 70. PMID: 20860819 | PMCID: PMC3092121
  • Terai K, Abbas T, Jazaeri A, Dutta A. CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis. Molecular cell. 2010;37(1): 143-9. PMID: 20129063 | PMCID: PMC2818832
  • Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nature reviews. Cancer. 2009;9(6): 400-14. PMID: 19440234 | PMCID: PMC2722839
  • Jha S, Dutta A. RVB1/RVB2: running rings around molecular biology. Molecular cell. 2009;34(5): 521-33. PMID: 19524533 | PMCID: PMC2733251
  • Karnani N, Taylor C, Malhotra A, Dutta A. Genomic study of replication initiation in human chromosomes reveals the influence of transcription regulation and chromatin structure on origin selection. Molecular biology of the cell. 2009;21(3): 393-404. PMID: 19955211 | PMCID: PMC2814785
  • Lee Y, Shibata Y, Malhotra A, Dutta A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes & development. 2009;23(22): 2639-49. PMID: 19933153 | PMCID: PMC2779758
  • Shibata Y, Malhotra A, Bekiranov S, Dutta A. Yeast genome analysis identifies chromosomal translocation, gene conversion events and several sites of Ty element insertion. Nucleic acids research. 2009;37(19): 6454-65. PMID: 19710036 | PMCID: PMC2770650
  • Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes & development. 2008;22(18): 2496-506. PMID: 18794347 | PMCID: PMC2546691
  • Jha S, Shibata E, Dutta A. Human Rvb1/Tip49 is required for the histone acetyltransferase activity of Tip60/NuA4 and for the downregulation of phosphorylation on H2AX after DNA damage. Molecular and cellular biology. 2008;28(8): 2690-700. PMID: 18285460 | PMCID: PMC2293106
  • Lew D, Burke D, Dutta A. The immortal strand hypothesis: how could it work? Cell. 2008;133(1): 21-3. PMID: 18394982
  • Abbas T, Jha S, Sherman N, Dutta A. Autocatalytic phosphorylation of CDK2 at the activating Thr160. Cell cycle (Georgetown, Tex.). 2007;6(7): 843-52. PMID: 17361108
  • Hook S, Lin J, Dutta A. Mechanisms to control rereplication and implications for cancer. Current opinion in cell biology. 2007;19(6): 663-71. PMID: 18053699 | PMCID: PMC2174913
  • Karnani N, Taylor C, Malhotra A, Dutta A. Pan-S replication patterns and chromosomal domains defined by genome-tiling arrays of ENCODE genomic areas. Genome research. 2007;17(6): 865-76. PMID: 17568004 | PMCID: PMC1891345
  • Lee Y, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes & development. 2007;21(9): 1025-30. PMID: 17437991 | PMCID: PMC1855228
  • Lin J, Dutta A. ATR pathway is the primary pathway for activating G2/M checkpoint induction after re-replication. The Journal of biological chemistry. 2007;282(42): 30357-62. PMID: 17716975
  • Machida Y, Dutta A. The APC/C inhibitor, Emi1, is essential for prevention of rereplication. Genes & development. 2007;21(2): 184-94. PMID: 17234884 | PMCID: PMC1770901
  • Sivaprasad U, Machida Y, Dutta A. APC/C--the master controller of origin licensing? Cell division. 2007;2 8. PMID: 17319958 | PMCID: PMC1810247
  • Zhu W, Ukomadu C, Jha S, Senga T, Dhar S, Wohlschlegel J, Nutt L, Kornbluth S, Dutta A. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes & development. 2007;21(18): 2288-99. PMID: 17761813 | PMCID: PMC1973143
  • Abbas T, Dutta A. CDK2-activating kinase (CAK): more questions than answers. Cell cycle (Georgetown, Tex.). 2006;5(10): 1123-4. PMID: 16687928
  • Kim H, Lee Y, Sivaprasad U, Malhotra A, Dutta A. Muscle-specific microRNA miR-206 promotes muscle differentiation. The Journal of cell biology. 2006;174(5): 677-87. PMID: 16923828 | PMCID: PMC2064311
  • Machida Y, Chen Y, Machida Y, Malhotra A, Sarkar S, Dutta A. Targeted comparative RNA interference analysis reveals differential requirement of genes essential for cell proliferation. Molecular biology of the cell. 2006;17(11): 4837-45. PMID: 16957053 | PMCID: PMC1635399
  • Machida Y, Machida Y, Chen Y, Gurtan A, Kupfer G, D'Andrea A, Dutta A. UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Molecular cell. 2006;23(4): 589-96. PMID: 16916645
  • Senga T, Sivaprasad U, Zhu W, Park J, Arias E, Walter J, Dutta A. PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. The Journal of biological chemistry. 2006;281(10): 6246-52. PMID: 16407252
  • Zhu W, Dutta A. Activation of fanconi anemia pathway in cells with re-replicated DNA. Cell cycle (Georgetown, Tex.). 2006;5(20): 2306-9. PMID: 17102625
  • Zhu W, Dutta A. An ATR- and BRCA1-mediated Fanconi anemia pathway is required for activating the G2/M checkpoint and DNA damage repair upon rereplication. Molecular and cellular biology. 2006;26(12): 4601-11. PMID: 16738325 | PMCID: PMC1489121