Research interests
Keywords: ATM in Radiation signaling; Chromatin structure and DNA damage response; Telomeres
Our major research interest is identification and characterization of tumor cells specific targets for radiosensitization. The combination of radiation genetics and biology tries to understand the relationship between DNA sequence and ionizing radiation sensitivity. Signal transduction pathways activated by the DNA damage response are the primary determinants of cell survival and transformation. Our research interests are focused on understanding the DNA damage response that has evolved to optimize cell survival following DNA damage. The goal of our research is to characterize the critical factor(s) that maintain genome stability after ionizing radiation exposure. The DNA damage response involves the actions of DNA repair proteins together with checkpoint events that slow down or arrest cell-cycle progression while the damage is being removed. Our aim is to determine – at the molecular level – how cells detect ionizing radiation-induced DNA damage then trigger the DNA damage response. We are specifically interested in defining the mechanisms by which chromatin modifications function to regulate the cellular response to DNA damaging agents, specifically ionizing radiation.
Recent Publications:
Kumar R, Hunt CR, Gupta A, Nannepaga S, Pandita RK, Shay JW, Bachoo R, Ludwig T, Burns DK, Pandita TK. Purkinje cell-specific males absent on the first (mMof) gene deletion results in an ataxia-telangiectasia-like neurological phenotype and backward walking in mice. Proc Natl Acad Sci U S A. 2011, 108:3636-41
Feng Z, Scott SP, Bussen W, Sharma GG, Guo G, Pandita TK, Powell SN. Rad52 inactivation is synthetically lethal with BRCA2 deficiency. Proc Natl Acad Sci U S A. 2011, 108:686-91
Liu H, Takeda S, Kumar R, Westergard TD, Brown EJ, Pandita TK, Cheng EH, Hsieh JJ. Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint. Nature. 2010, 467:343-6.
Sharma GG, So S, Gupta A, Kumar R, Cayrou C, Avvakumov N, Bhadra U, Pandita RK, Porteus MH, Chen DJ, Cote J, Pandita TK. MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair. Mol Cell Biol. 2010, 30:3582-95.
Zeng S, Xiang T, Pandita TK, Gonzalez-Suarez I, Gonzalo S, Harris CC, Yang Q. Telomere recombination requires the MUS81 endonuclease. Nat Cell Biol. 2009, 11:616-23.
Most Important papers
Gupta A, Guerin-Peyrou TG, Sharma GG, Park C, Agarwal M, Ganju RK, Pandita S, Choi K, Sukumar S, Pandita RK, Ludwig T, Pandita TK. The mammalian ortholog of Drosophila MOF that acetylates histone H4 lysine 16 is essential for embryogenesis and oncogenesis. Mol Cell Biol. 2008, 28:397-409.
Richard DJ, Bolderson E, Cubeddu L, Wadsworth RI, Savage K, Sharma GG, Nicolette ML, Tsvetanov S, McIlwraith MJ, Pandita RK, Takeda S, Hay RT, Gautier J, West SC, Paull TT, Pandita TK, White MF, Khanna KK. Single-stranded DNA-binding protein hSSB1 is critical for genomic stability. Nature. 2008, 453:677-81.
Hunt CR, Pandita RK, Laszlo A, Higashikubo R, Agarwal M, Kitamura T, Gupta A, Rief N, Horikoshi N, Baskaran R, Lee JH, Löbrich M, Paull TT, Roti Roti JL, Pandita TK. Hyperthermia activates a subset of ataxia-telangiectasia mutated effectors independent of DNA strand breaks and heat shock protein 70 status. Cancer Res. 2007, 67:3010-7.
Hunt CR, Dix DJ, Sharma GG, Pandita RK, Gupta A, Funk M, Pandita TK. Genomic instability and enhanced radiosensitivity in Hsp70.1- and Hsp70.3-deficient mice. Mol Cell Biol. 2004, 24:899-911.
Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA. hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell. 2001, 107:149-59.
Scherthan H, Jerratsch M, Dhar S, Wang YA, Goff SP, Pandita TK. Meiotic telomere distribution and Sertoli cell nuclear architecture are altered in Atm- and Atm-p53-deficient mice. Mol Cell Biol. 2000, 20:7773-83.
