Contact Information:

• Tej K. Pandita
  Washington University School of Medicine
  4511 Forest Park
  St Louis, MO 63108

  Phone: 314-747-5461 (office)
  314-362-9783 (lab)
  Fax: 314-362-9790
  E-mail: pandita@wustl.edu
  

Education:

• BSc - Kashmir University, India
• MSc - Kashmir University, India
• PhD - Panjab University, India

Research Interests:

The challenges of radiation biology in my laboratory are focused around:

• Chromatin modifications and epigenetics in ionizing radiation response.
• DNA damage and repair
• Ataxia-telangiectasia mutated
• Telomere metabolism
• Genetic predisposition to radiation toxicity

Our long-term goal is to understand how radiocurability of tumor cells can be enhanced. Most tumor cells have telomerase activity and ATM is involved in sensing ionizing radiation induced DNA damage. The focus of our research is to determine how ATM functions and telomere metabolism are regulated. Telomeres are maintained by telomerase and the dynamics of human telomeres have been implicated in cellular senescence and cancer. We have demonstrated that ATM influences the telomere chromatin structure. We are currently testing how chromatin-modifying factors regulate ATM mediated functions that coordinate the repair of DNA damage specifically at telomeres. The ultimate goal is to determine whether such factor/s are involved in sensing ionizing radiation-induced damage.

Selected Publications

• Pandita RK, Sharma GG, Laszlo A, Hopkins KM, Davey S, Chakhparonian M, Gupta A, Wellinger RJ, Zhang J, Powell SN, Roti Roti JL, Lieberman HB and Pandita TK (2006). Mammalian Rad9 plays a role in telomere stability, S- and G2-phase specific cell survival and homologous recombinational repair. Mol Cell Biol. 26:1850-1864.
• Bredemeyer AL, Sharma GG, Huang C-Y, Helmink BA, Nuskey B, Walker LM, Pandita TK, Bassing CH, and Sleckman BP (2006). ATM stabilizes DNA double strand break complexes during V(D)J recombination. Nature (2006) (in press).
• Puc J, Keniry M, Li HS, Pandita TK, Choudhury AD, Memeo L, Mansukhani M, Murty VVVS, Gaciong Z, Meek SEM, Piwnica-Worms H, Hibshoosh H and Parsons R (2005) Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell 7:193-204.
• Gupta A, Sharma GG, Young HCR, Agarwal M, Smith E.R., Paull TT, Lucchesi JC, Khanna KK, Ludwig T and Pandita TK (2005). Involvement of Human MOF in ATM Function. Mol. Cell. Biol. 25:5292-5305.
• Seo J, Chung YS, Sharma GG, Moon E, Burack WR, Pandita TK and Choi K (2005). Overexpression of the DNA replication licensing protein Cdt1 causes genomic instability and enhances tumorigenecity in p53 null mice. Oncogene 24: 8176-8186.
• Ziv S, Brenner O, Amariglio N, Smorodinsky NI, Galron R, Carrion DV, Zhang W, Sharma GG, Pandita RK, Agarwal M, Elkon R, Katzin N, Bar-Am I, Pandita TK, Kucherlapati R, Rechavi G, Shiloh Y, and Barzilai A (2005). Impaired genomic stability and increased oxidative stress exacerbate different features of AT. Hum Mol Genet 14:2929-2943.
• Pandita TK (2005) Role of HSPs and telomerase in Radiotherapy. Int Jr Hyperthermina 21: 689-694.
• Hunt CR, Dix DJ, Sharma GG, Pandita RK, Gupta A, Funk M, and Pandita TK (2004) Genomic instability and enhanced radiosensitivity in Hsp70.1/3-deficient mice. Mol Cell Biol 24:899-911.
• Richardson C, Horikoshi N and Pandita TK (2004) DNA double-strand break response network in meiosis. DNA Repair 3:1149-1164.
• Shahrabani-Gargir L, Pandita TK and Werner H (2004) Ataxia-telangiectasia mutated gene controls insulin-like growth factor I receptor gene expression in a deoxyribonucleic acid damage response pathway via mechanisms involving zinc-finger transcription factors Sp1 and WT1. Endocrinology 145:5679-5687.
• Pandita T.K.A multifaceted role for ATM in genome maintenance. Expert Reviews in Molecular Medicine. 5: 1-21 (2003).
• Sharma GG, Hwang K-K., Pandita RK, Gupta A, Dhar S, Prenteau M, Agarwal M, Worman HJ, Wellinger RJ, and Pandita TK. Human heterochromatin protein 1 isofroms HP1 and HP1 interfere with hTERT-telomere interactions and correlates with changes in cell growth and reponse to ionizing radiation. Mol Cell Biol 23: 8363-8376 (2003).
• Sharma G.G, Gupta A., Scherthan H., Dhar S., Wang H., Gandhi V., Iliakis G., Young C.S.H., and Pandita T.K. hTERT associating with telomeres reduces spontaneous chromosome damage and enhances DNA repair. Oncogene 22:130-146 (2003).
• Pandita T.K. ATM function and Telomere stability. Oncogene 21:611-618 (2002).
• Vaziri H., Dessain S., NgEaton E., Imai SI, Frye R., Pandita T.K., Guarente L., and Weinberg R.A. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 107:149-159 (2001).
• Vafa O., Wade M., Kern S., Beeche M., Pandita T.K., Hampton G.M. and Wahl G.M. c-Myc can induce DNA damage, increases reactive oxygen species, and mitigates p53 function: a mechanism for oncogene-induced genetic instability. Mol. Cell. 9:1031-1044 (2002).
• Ferguson A.T., Evron E., Umbricht C.B., Pandita T.K., Chan T.A., Hermeking H., Marks J.R., Lambers A.R., Futreal P.A., Stampfer M.R., Sukumar S. High frequency of hypermethylation at the 14-3-3? locus leads to gene silencing in breast cancer. PNAS USA 97:6049-6054 (2000).
• Kharbanda S., Kumar V., Dhar S., Pandey P., Chen C., Yuan Y., Whang Y., Saywers C., Strauss W., Pandita T.K., Weaver D. and Kufe D. Regulation of the EST2 telomerase catalytic subunit by the c-Abl protein tyrosine kinase. Current Biology 10:568-575 (2000).
• Pandita T.K., Lieberman H.B., Lim D-S., Dhar S., Zheng W., Taya Y., and Kastan M.B. Ionizing radiation activates the ATM kinase throughout the cell cycle. Oncogene 20:1386-1391 (2000).
• Vaziri H., Squire J.A., Pandita T.K., Bradley G., Kuba R.M., Nolan G.P., Zhang H., Gulyas S., Hill R.P. and Benchimol S. Analysis of genomic integrity and p53 dependent G1 checkpoint in telomerase induced extended life span fibroblast (TIELF) cells. Mol. Cell. Biol. 19:2373-2379 (1999).
• Sawant S.G., Gregiore V., Dhar S., Umbricht C.B., Cvilic S., Sukumar S. and Pandita T.K. Telomerase activity as a measure for monitoring radiocurability of tumor cells. FASEB J. 13:1047-1054 (1999).
• Pandita T.K., Westphal C.H., Anger M., Sawant S.G., Geard C.R., Pandita R.K., and Scherthan H. Atm inactivation results in aberrant telomere clustering during meiotic prophase. Mol. Cell. Biol. 19:5096-5105 (1999).
• Smilenov L.B., Dhar S., and Pandita T.K. Altered telomere nuclear matrix interactions and nucleosomal periodicity in cells derived from individuals with ataxia telangiectasia before and after ionizing radiation treatment. Mol. Cell. Biol. 19:6963-6971 (1999).
• Morgan S.E., Lovly C., Pandita T.K., Shiloh Y., and Kastan M.B. Fragments of ATM which have dominant-negative or complementing activity. Mol. Cell. Biol. 17:2020-2029 (1997).
• Smilenov L.B., Morgan S.E., Mellado W., Sawant S.G., Kastan M.B. and Pandita T.K. Influence of ATM function on telomere metabolism. Oncogene 15:2659-2666 (1997).
• Pandita T.K., Pathak S., and Geard C. Chromosome end associations, telomeres and telomerase activity in ataxia telangiectasia cells. Cytogenet. Cell Genet. 71:86-73 (1995).
• Pandita T.K. and Hittelman W.N. The contribution of DNA and chromosome repair deficiencies to the radiosensitivity of ataxia telangiectasia. Radiat. Res. 131:214-223 (1992).