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My research is focused on understanding contribution of epigenome to cancer progression and identifying new venues for therapy and diagnostic tools. My lab utilizes cutting-edge epigenomic approaches to study chromatin state changes and higher order chromatin structure during evolution of tumor cells. Over the years, I have developed expertise in studying epigenetic processes by identifying factors that perform epigenetic functions, identifying their roles in cellular events that regulate normal organ development and abnormal cell growth during tumorigenesis. The highlights of my current research include comprehensive understanding of chromatin state reprogramming during early stages of melanoma (Cell Reports 2017), colon cancer (Orouji et al, Biorxiv 2020) and during metastasis (Biorxiv 2019) as well as identification of major drivers of pre-malignant to malignant to metastatic transitions (Cancer Discovery 2015; Nature Communications 2019; Biorxiv 2018). I also co-led several studies with other investigators (Cancer Cell, 2020; Nature Communications, 2019; Journal of Clinical Investigation 2015; Stem Cell Reports 2017). Previously, as a trainee I defined a DNA-repair mediated DNA demethylation process (Cell 2008), and discovered its role in colon cancer initiation (Cell 2010). My PhD work deciphered roles of DNA and histone methyltransferases in early embryonic development (MCB 2006, G&D 2007 and JBC 2010). We have optimized methods for high-throughput ChIP-sequencing in small amount of cell numbers and tissue samples (Terranova et al, JoVE 2018). We have systematically generated chromatin state maps into 9 other tumor types and have generated > 3000 ChIP-Seq datasets (usually undertaken by large consortium efforts). These data have led to the discovery of several new concepts including a strategy to stratify patients based on their epigenomic content for specific therapies (4 papers in review in high impact journals). We are also investing heavily in the single cell epigenomics (Abbas et al, Biorxiv, 2020) Current and future projects include: 1) utilize cutting-edge computation approaches to fully exploit these data; 2) examine epigenetic aberrations at the single-cell resolution; 3) functionalize ‘cancer-specific’ epigenetic elements using CRISPR-Cas9 based epigenetic editing approaches and 4) evaluate aberrations in higher-order chromatin structure.
研究兴趣
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