Our Science – Varticovski Website
Lyuba Varticovski, M.D.
Our work has been focused on drug development, mechanisms of synergy and antagonism using combination of molecular targeted agents and conventional chemotherapies, and drug resistance. In the last several years, cancer stem cells have been identified as a subpopulation of cells responsible for tumor recurrence and drug resistance. Substantial effort towards isolation of cancer stem cells has led to the identification of tumor-specific markers, but characterization of these cells and mechanisms of their resistance to drugs has been largely descriptive. We came to appreciate that in order to develop effective therapies for cancer stem cells, we need a better understanding of stem cell biology and specifically regulation of stemness and differentiation. While gene expression profiling is the end result of multiple processes, the accessibility of transcription factors (TFs) to DNA ultimately controls stemness, reprogramming and differentiation. The LRBGE has pioneered global unbiased landscape analysis of the accessible genome (i.e., all sites in the genome that are accessible to TFs at any time) by combining DNase I hypersensitivity assays with deep sequencing (DHS-seq). In-depth bioinformatic annotation of DNase I accessible sites to all known human and mouse genome sites provides an unbiased view of changes in accessibility for all regulatory elements in any cell type at any given time. This is a powerful tool for identification of novel sites in distant and proximal enhancers and promoters of epigenetic changes that mark stemness and differentiation. We focused on establishing the landscape of all accessible genome in cell lines that are enriched in cancer stem cells and are resistant to conventional chemotherapeutic agents, as well as osteogenic differentiation of inducible pluripotent cells (iPS) cells derived from normal individuals and patients with inheritable disorders, such as osteogenesis imperfecta (OI). Gene replacement therapy using these cells may save many lives and provide an unlimited source of stem cells for regenerative therapy.
This page was last updated on 3/5/2013.