Sathees C. Raghavan

Associate Professor

Ph.D.

Banaras Hindu University, India, 1999

Postdoctoral Research

University of Southern California, Los Angeles, USA 1999-2006
Tel: +91-80-2293 2674
Email: sathees@biochem.iisc.ernet.in



 Research

  • Cancer Genetics
  • Genomic instability
  • DNA repair and recombination

Mechanism of generation and development of chromosomal translocations in human leukemia and lymphoma

Chromosomal translocations are one of the major genomic abnormalities found in different cancers especially in the haematological malignancies, lymphoma and leukemia. My laboratory aims to determine the mechanism of generation of such chromosomal translocations, involving several oncogenes. We study how and why, the DNA breaks at some specific sites in the genome and try to characterize such fragile regions. The steps involved in the progression of such translocation bearing cells into a complete cancerous state are also being investigated.

Role of RAG proteins in genomic instability

The RAG complex (RAG1 and RAG2 proteins), is a sequence specific nuclease involved in generating the immunoglobulin/TCR diversity during V(D)J recombination. RAGs have been shown to cause some chromosomal translocations in T-cell leukemia. We have previously identified a novel property of the RAG complex being a structure specific nuclease as opposed to its classical function. We are in the process of identifying the importance of sequences influencing the RAG cleavage on altered DNA structures, in the context of the human genome. Further mechanistic details of such a property are also being explored. These studies could explain the genomic instability related to lymphoid tissues.

Understanding mechanism of NHEJ in tissues and cancer cells

DNA double strand breaks are the most deleterious damages incurred by the cell. These are primarily repaired by two pathways, homologous recombination (HR) and nonhomologous end joining (NHEJ), of which the latter is predominant in higher eukaryotes. My laboratory works on understanding the mechanism of NHEJ in normal and cancer tissues. Besides, we also study the mechanism of NHEJ in different leukemia and lymphoma, especially due to the high genomic rearrangements present in them. Apart from this, single-strand break repair pathways in different cells are also being investigated.

Screening of synthetic and natural compounds for anti-cancer properties and understanding their mode of action

Another area of research in my laboratory is the screening of various chemically synthesized and naturally derived compounds for anti-cancer properties. We also study their mode of action at the molecular level. The more potent compounds are further tested in vivo in mice models bearing various tumors. Our studies have identified many such promising candidates, some of which are currently investigated in vivo. We also aim to design compounds which are target specific, against proteins which are upregulated specifically in cancers.

 Lab Members


 Key Publications

  • Mridula Nambiar, Mrinal Srivastava, Vidya Gopalakrishnan, Sritha K. Sankaran, Sathees C. Raghavan (2013) G-quadruplex Structures Formed at the HOX11 Breakpoint Region Contribute to its Fragility During t(10;14) Translocation in T-cell Leukemia. Mol. Cell. Biol. [Epub ahead of print]
  • Mridula Nambiar, Sathees C. Raghavan (2013) Chromosomal translocations among the healthy human population: implications in oncogenesis. Cell. Mol. Life Sci., 70(8):1381-92.
  • Kavitha CV, Mridula Nambiar, Pavan B Narayanaswamy, Elizabeth Thomas, Ujwal Rathore, Ananda Kumar CS, Bibha Choudhary, Rangappa KS, Sathees C. Raghavan (2013) Propyl-2-(8-(3,4-Difluorobenzyl)-2',5'-Dioxo-8 Azaspiro[Bicyclo[3.2.1] Octane-3,4'-Imidazolidine]-1'-yl) Acetate Induces Apoptosis in Human Leukemia Cells through Mitochondrial Pathway following Cell Cycle Arrest. PLoS One. 8(7):e69103.
  • Mrinal Srivastava, Mridula Nambiar, Sheetal Sharma, Subhas S. Karki, G. Goldsmith, Mahesh Hegde, Sujeet Kumar, Monica Pandey, Ram K. Singh, Pritha Ray, Renuka Natarajan, Madhura Kelkar, Abhijit De, Bibha Choudhary, Sathees C. Raghavan (2012) An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell, 151:1474-87.
  • Mayilaadumveettil Nishana and Sathees C. Raghavan (2012) A non-B DNA can replace heptamer of V(D)J recombination when present along with a nonamer: implications in chromosomal translocations and cancer. Biochem. J., 448:115-25.
  • Mridula Nambiar and Sathees C. Raghavan (2012) A novel mechanism of RAG cleavage induces breaks at BCL2 minor breakpoint cluster region during t(14;18) translocation in follicular lymphoma. J. Biol. Chem., 287:8688-701.
  • Kishore K. Chiruvella, Robin Sebastian, Sheetal Sharma, Anjali A. Karande, Bibha Choudhary and Sathees C. Raghavan (2012) Nonhomologous DNA End-Joining in Cell-free Extracts of Post Implantation Embryos of Mice. J. Mol. Biol., 417:197-211.
  • Sheetal Sharma, Bibha Choudhary and Sathees C. Raghavan (2011) Nonhomologous DNA End Joining is Most Efficient in Lungs among Somatic Tissues, and is Equivalent to Germ Cells, Cell. Mol. Life. Sci. 68:661-76.
  • Mridula Nambiar and Sathees C. Raghavan (2011) How DNA breaks during chromosomal translocations in cancer? Nucleic Acids Res., 39:5813-25.
  • Mridula Nambiar, Goldsmith, Balaji T. Moorthy, Mamata V. Joshi, Bibha Choudhary, Michael R. Lieber, Ramakrishna V. Hosur and Sathees C. Raghavan (2011) Characterization of G-quadruplex Structure BCL2 Major Breakpoint Region of t(14;18) translocation in follicular lymphoma. Nucleic Acids Res., 39:936-48.
  • Tadi Satish Kumar, Vijayalakshmi Kari, Bibha Choudhary, Mridula Nambiar, Akila T.S. and Sathees C. Raghavan (2010) Anti-apoptotic Protein, BCL2, Downregulates Nonhomologous DNA End Joining in Cancer Cells, J. Biol. Chem., 285: 32657-32670 32657-32670 .
  • Abani Kanta Naik, Michael R. Lieber and Sathees C. Raghavan (2010) Cytosines, but not purines, determine RAG induced breaks on heteroduplex DNA Structures: Implications for genomic instability, J. Biol. Chem., 285: 7587-97.