Research Projects

In the study "Understanding transcriptional and epigenetic modulation of AMPK subunit expression during acquisition of cancer chemo-resistance" we aim to decipher the engimatic expression levels of different AMPK subunit isoforms in breast cancer and glioblastoma. AMPK is central metabolic regulator and plays a critical role in modulating cancer metabolism and acquisition of chemoresistance. AMPK comprises of 3 subunits, α, β and γ, each of which can exist in different isoforms and can make 12 different heterotrimeric complexes. Despite several studies examining the AMPK substrates and downstream signaling pathways, there are few researches to understand the regulation of AMPK subunit expression. It has been reported that AMPK subunits are expressed in cell and tissue specific manner and can play a pro or anti cancer role during tumorigenesis. In our preliminary in-silico analysis we observed varied expression levels of AMPK subunits in breast cancer and glioblastoma. This led us to hypothesize that there must be precise transcriptional and epigenetic mechanisms to regulate the differential expression of these subunit isoforms. Therefore we plan to conduct experiments to check AMPK subunit experiments under different stress conditions in chemosensitive and chemoresistant cell types.. Thereafter we shall look for precise transcription factors and epigenetic modifiers involved in controlling expression by performing reverse chip analyses. Further we shall examine the intracellular localization of unique AMPK heterotrimeric complexes under different stress conditions. We anticipate successful completion of this project will provide significant information about the mechanisms involved in heterotrimeric composition of AMPK and its relavance in acquisition of cancer chemoresistance. This knowledge can then be leveraged to know substrates of unique AMPK complexes and to therapeutically target them with isoform specific inhibitors.