PhD. Biochem., California Institute of Technology
Regulation of DNA replication in mammalian cells. Eukaryotic chromosomes contain multiple origins of DNA replication. The control of firing of these origins, their mutual interactions, and their relationship to gene transcription are still mostly unknown. My lab is using SV40 origin as a model to address these questions by designing experiments with interactions between origins and between origins and transcription elements.
Study of regulome in mammalian cells. All genes must be tightly regulated by regulatory elements. The aim of the research is to find these elements for regulation of cell differentiation and for alterations in cellular programs such as in cancer cells. Many important genes are expressed at such low level that cloning by cDNA route is not able to identify them. To answer these challenging problems we developed the nuclease-hypersensitive-PCR fingerprinting technique to fish out these elements very efficiently. We have cloned many elements that are responsive to cell differentiation program and from these elements identify novel genes participating in the differentiation program.
Study of methylome in mammalian cells. Epigenetic mechanisms are the key linking phenotypes and genotypes. One of the major epigenetic mechanisms is DNA methylation. We have used methylation-sensitive PCR fingerprinting technique to identify tissue-specific methylated sequences from the mouse genome and to identify the biological meaning of these epigenetic changes. In particular we are interested in chromatin domains demarcated by these epigenetic changes that include DNA methylation and histone modifications.