Anindya Dutta, MD, PhD

Anindya Dutta, MD, PhD

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G1-S transition in cancer cells and mis-regulation in cancer; regulation of chromosomal replication

My laboratory focuses on the regulation of the G1-S transition in cancer cells and implications of the mis-regulation of this process on genomic stability.  We examine how various replication initiation factors co-operate with each other to ensure that replication occurs once and only once in the cell-cycle.  We have focused on a negatively acting factor called geminin that interferes with replication initiation and discovered that it selectively inhibits the replication of episomes.  Such anti-initiation factors could be useful for inhibiting the maintenance of cancer cell episomes, e.g. those arising from Epstein Barr Virus in EBV-dependent lymphomas or from amplified cellular genes in a wide variety of cancers. Conversely, de-regulated expression of some positively acting initiation factors like Cdt1 lead to over-replication of the genome, particularly in p53-deficient cells, leading to the hypothesis that such over-replication in  a p53-deficient cancer cells might lead to gene amplification.  We recently discovered that statins (widely taken for inhibition of cholesterol biosynthesis) inhibit the action of cyclin-dependent kinases and prostate cancer cell proliferation, which has led us to investigate whether these drugs could be chemo-prophyllactic for prostate cancer development or progression.