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Cellular Studies

At the cellular level, we focus on nuclear architecture as it supports proliferation and differentiation of lineage-committed cells and stem cells, as well as compromised nuclear structure that characterizes cancer cells. These studies analyze subnuclear organization of gene regulatory machinery including intranuclear trafficking of transcription factors, interactions with cell-signaling responsive co-factors and chromatin remodeling enzymes. We apply systems biology strategies to define gene regulatory networks and signaling pathways.

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Molecular Studies

At the molecular level, we are defining epigenetic chromatin modifications at gene loci during interphase (‘Histone Code’) and mitosis (‘Bookmarking’) to understand the transcriptional regulation of tissue-specific genes, cell cycle control, and cell fate determination. Our studies center on transcriptional master regulators and post-transcriptional mechanisms (including microRNAs and non-long-coding RNAs) that together control osteogenesis, hematopoiesis, and the pluripotent state of embryonic stem cells. The aberrant loss- or gain-of-functions of these gene regulatory factors in leukemias, as well as in metastasizing breast, prostate, and bone cancers, are being actively pursued.

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Methods & Techniques

Experimental systems include CRISPR-edited cell lines and mouse models, cancer stem cells, cancer patient-derived organoids, and xenografts. Experimental approaches include genome analysis (single-cell sequencing, RNA-seq, ATAC-seq, CHiRP, PRO-seq, Cut and Run, BioID, and chromosome conformation capture), spatial transcriptomics (NanoString), multispectral imaging (CODEX), degron strategies, and analysis of patient-derived tissue specimens.