Our research group examines the molecular etiology of cancer, the basic biology of stem cells as it relates to regenerative medicine, and the biology of bone development and skeletal disorders.
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.
At the molecular level, we are defining epigenetic chromatin modifications at gene loci during interphase (‘Histone Code’) and mitosis (‘Bookmarking’) to understand 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) 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.
We utilize a variety of cutting-edge cellular, molecular, biochemical and genetic approaches to address our biological questions. The in vivo mouse models we develop, together with ex vivo bone organ cultures and primary cell culture, permit pursuit of translational approaches to treat skeletal and hematopoietic disorders. Our experimental strategies involve state-of-the-art genomics (DeepSeq, ChIPSeq, Affymetrix) and proteomics analyses, as well as high resolution and live-cell imaging fluorescence microscopy.