Molecular Biology of Cancer - Dr. N.Sudhakar
1) Somatic mutations in PI3KCA in Breast Cancer
Our study focuses on detection of somatic mutations in PI3K catalytic subunit alpha (PI3KCA) in breast cancer. The class IA Phosphotidylinositide 3-kinase (PI3K) is a family of lipid kinases that exist as a heterodimer consisting of a unique catalytic subunit (p110?, ? or ?) along with one of shared regulatory subunits (p85?, p85?, or p55?). PI3-kinases phosphorylate the 3"-inositol position on a variety of membrane associated phosphatidylinositols (PI). The PI3K family of enzymes regulate diverse biological functions such as cell growth, proliferation, differentiation and survival. Dysregulated PI3K signaling either due to somatic mutation in PI3KCA or amplification of PI3K gene can lead to cancer. Hot spot mutations in PI3KCA has been studied by PCR and sequencing methods.
2) Single Nucleotide Polymorphisms (SNPs) in DNA repair genes and susceptibility to cancers
A Single Nucleotide Polymorphism or SNP, is a genetic change, or variation in a DNA sequence that occurs with more than one percent in a population. Inter individual variability in DNA repair capacity is an important factor influencing an individual's cancer risk. DNA repair gene polymorphisms may contribute to this variation. The X-ray repair cross-complementing group 1 (XRCC1) is an essential DNA repair gene involved in base excision repair (BER). The XRCC1 gene is present on chromosome number 19 (19q13.2). The protein encoded by this gene is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. We have done a preliminary study on SNPs in XRCC1 gene and susceptibility to breast cancer by PCR and Restriction analysis methods.
3) Toll-like receptor signaling in Cancer
Toll-like receptors (TLR), a mammalian homologue of the Drosophila Toll protein, are the best characterized family of pattern-recognition receptors (PRR), which sense foreign material derived from bacteria or virus. Toll-like receptors (TLR) are a family of transmembrane receptors characterized by a cytoplasmic Toll/Interleukin-1 receptor homology (TIR) signaling domain and an external antigen recognition domain. In humans, there are ten functional TLRs (TLR1 to TLR10) classified according to their subcellular localization. The endogenous and exogenous ligands for TLR are well characterized. But the TLR expression, cytokines and signaling events activated in cancer is not well studied. So, we are focusing on studying TLR expression in different types of cancer cells and the signaling activated in cancer cells for therapy.
Projects submitted by Dr.N.Sudhakar under Review: One
"To Investigate the Toll-like receptor (TLR) Signalling in Breast Cancer and evaluate the use of multiple TLR ligands for therapy” - Applied under DST-FAST TRACK scheme. Budget: 23 Lakhs