Nagarajan lab is interested in unravelling the mechanisms of enhancer regulation and the role of transcription factors in mediating the progression to drug resistance and metastasis in aggressive cancers. We utilise single cell analyses, functional genomic technologies, quantitative chromatin-based proteomics and CRISPR-Cas9 assays to decipher the mechanisms of transcription. We work on the following projects:
Epigenetic proteins in driving endocrine resistance in breast and prostate cancers
We established CRISPR-Cas9 based genome-wide knockout screens to identify the proteins involved in promoting or deregulating endocrine resistance in breast cancers upon Tamoxifen and Fulvestrant treatment and in prostate cancers upon Enzalutamide treatment. This screen identified multiple chromatin architecture proteins involved in controlling the resistance of cell growth during drug treatments. Some of these proteins are amplified/mutated in breast and prostate cancers, especially prevalent in secondary tumours. Given the importance of these proteins clinically and evident from molecular analyses, we aim to identify the mechanisms behind the regulation of endocrine resistance by these chromatin-associated proteins and how these proteins interact with nuclear receptors (estrogen and androgen receptor) to bring cell growth resistance towards treatments. We will employ cutting-edge technologies studying gene regulation and chromatin organization-based assays to understand how enhancer -promoter interactions and their deregulation are involved in these processes.