Dr. V. Ravikumar
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Research Interests |
Epigenetic Regulation in Lung Cancer
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Summary of the Research |
We have been interested in a family of enzymes named histone deacetylase (HDAC), which catalyzes the deacetylation of the acetyl lysine residue on histone tails. There are 18 members of human HDAC which can be divided into four classes. Class I, II and IV HDACs require zinc metal whereas Class III HDACs, which are named sirtuins, are NAD-dependent. Counteracting histone acetyltransferase (HAT), HDAC controls the histone acetylation level, structural modification of chromatin, and subsequent regulation of genes that are implicated in cell growth, proliferation, and differentiation. Furthermore, many non-histone proteins have been identified as HDAC substrates. Over expressed or sustained HDAC activity, occurring in some cancer cells, results in deacetylation of the histone tails. Histone deacetylation results in a more closed chromatin structure. Certain genes may become inaccessible to transcription factors and do not get transcribed. This is thought to be a mechanism for limiting or silencing tumor suppressor genes, such as p53, and genes for cyclin-dependent kinase inhibitors, such as p21. Epigenetic silencing of these genes may play a role in the risk of cancer development resulting in uncontrolled cell growth. Aberrant HDAC levels that limit or silence gene expression have been described in leukemias and lymphomas, as well as other malignancies.Numerous studies have demonstrated that inhibitions of HDAC offer therapeutic benefits. We are interested in studying the epigenetic control of gene expression by HDAC inhibitors in lung cancer therapy.
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