Our Faculty > Anindya Dutta

Anindya Dutta

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, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

DNA Replication and Genomic Instability in Cancer Cells

Research Description



Our lab studies the genetics and genomics of the cell-cycle in normal and cancer cells with an emphasis on microRNAs, DNA replication and DNA damage. The projects in the lab are summarized below: (1) We have focused on microRNAs that regulate cell-cycle progression during muscle differentiation or in prostate cancers, with a special emphasis on potential tumor suppressor microRNAs. We discover microRNAs that change under specific conditions using techniques like microarrays and cloning/high-throughput sequencing and identify the targets of the relevant microRNAs. (2) A better knowledge of how DNA replication is initiated or regulated in mammalian cells will allow us to devise (or discover) inhibitors that restrain DNA replication in cancer cells and understand how disorders in their regulation lead to genomic instability. For example, we map origins of replication in human cells using genome tiling arrays or high throughput sequencing and study how use of the origins is altered by chemotherapy drugs. We also study the how replication initiation-factors and cell-cycle regulators are regulated by ubiquitylation both in the normal cell-cycle and in response to DNA damage. (3) We study how the Tip60 acetyltransferase and tumor suppressor is involved in the normal response of a cell to DNA damage and how tumor producing viruses like Human Papilloma Virus subvert this response pathway. Similarly, we study how experimental anti-cancer drugs like MLN4924 de-regulate the cell-cycle to cause re-replication and DNA damage.

Selected Publications

  • 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
  • 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
  • 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
  • Abbas T, Dutta A. CDK2-activating kinase (CAK): more questions than answers. Cell cycle (Georgetown, Tex.). 2006;5(10): 1123-4. PMID: 16687928
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Sivaprasad U, Machida Y, Dutta A. APC/C--the master controller of origin licensing? Cell division. 2007;2 8. PMID: 17319958 | PMCID: PMC1810247
  • 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
  • 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
  • Lew D, Burke D, Dutta A. The immortal strand hypothesis: how could it work? Cell. 2008;133(1): 21-3. PMID: 18394982
  • 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
  • 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
  • Jha S, Dutta A. RVB1/RVB2: running rings around molecular biology. Molecular cell. 2009;34(5): 521-33. PMID: 19524533 | PMCID: PMC2733251
  • Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nature reviews. Cancer. 2009;9(6): 400-14. PMID: 19440234 | PMCID: PMC2722839
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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, 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
  • 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
  • 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
  • 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
  • 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