|Current Research Interests
The principal research interest of my laboratory is to understand the function of epigenetic modifications in regulation of DNA metabolic processes such as DNA replication and repair and their implication in maintenance of genomic integrity. In eukaryotes, DNA metabolic processes such as DNA replication, repair, recombination are tightly regulated by the packaging of DNA into chromatin and dynamic alterations in chromatin structure. This precise regulation is crucial for maintenance of genomic integrity. Our goal is to discover novel ways in which the chromatin structure is altered during DNA replication and DNA repair, and to understand how these chromatin dynamics regulate these key nuclear processes. For example, we have recently discovered a novel Histone H3 core domain modification Histone H3lysine 56 in mammalian cells and established its function in DNA damage signaling. Currently, we are working on deciphering the molecular functions of this modification in the DNA damage signaling pathway. The role of reversible acetylation and deacetylation of histones and non-histone proteins during DNA metabolic processes and how alterations in these modifications contribute to genomic instability and cancer development is not very well worked out. My laboratory is involved in understanding the role of histone acetylation/deacetylation in the overall process and its implication in cancer initiation and development.
We are also interested in understanding the functions of Sirtuin family of NAD-dependent protein deacetylases and how this class of protein may contribute to cancer development. We use yeast and human cell lines as model systems. Based on our findings in yeast system, we like to extend our working hypothesis to mammalian cells. Understanding role of epigenetic modifications in the maintenance of genomic integrity is critical in the prevention, diagnosis, and treatment of a number of pathologies, including cancer and other age related diseases. Given the strong correlation among chromatin modifications, altered genomic stability and development of cancer and other age related diseases, I hope our research will provide important insight into understanding these complex mechanisms.
Projects in progressUnderstanding the functions of Histone H3 lysine 56 acetylation and its role in cancer
initiation and progression.
A suppressor screen to uncover novel functions of fission yeast S. pombe Sirtuin Hst4: function of Sirtuins in regulation of DNA replication.
A yeast based screen for discovery of novel Sirtuin inhibitors as anti-cancer agents.
Project to be initiated
Regulation of macrophage inflammatory response by histone H3 lysine 56 acetylation
Sirtuin mediated transcriptional regulation of DNA replication.