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We study causal relationships between gene regulation, cell differentiation, and cancer. We are interested in stem cell engineering, single-cell technologies, and systems biology models. Combining computational and experiment advances, we discovered genetic differences of early embryonic development among humans, mice, and cows (Research Highlight, Nature 464: 1248). We introduced "comparative epigenomics" - using cross-species epigenomic comparison to annotate the genomes (Xiao et. al., Cell, in press). Key words: stem cell, cancer, statistics, computation, epigenomics, evolution. |
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Why a systems biology approach? One thing we look at is how gene regulatory networks (GRNs) orchestrate the level of expression of each gene by controlling where, when and how vigorously that gene will produce RNAs and proteins. To study GRNs, one needs not just DNA, but RNAs, proteins, and their biochemical modifications and interactions, hence systems biology. An example In a comparative study, we found that close to forty percent of the genes shared by humans, mice and cows have different expression patterns in the early stages of embryonic development. We traced these differences to a set of specific evolutionary changes of the genomes. This work suggested that more than one GRN can guide early embryonic development, and we are working on using such information to make pluripotent cells from adult cells more quickly, efficiently and inexpensively. See cover article in Genome Research, and research highlight in Nature . Current work One of our goals is to understand the evolutionary changes and principles in a wide range of mammalian GRNs. We are in the process of adding epigenetic data in the pluripotent cells of humans, mice, pigs and opossums to the multispecies comparison. (Read more) | |
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Comparative analysis of transcription networks The control of gene transcription is a crucial component in regulating many important biological processes. For example, in the early stages of development, cell fate decisions and differentiation programs are often controlled by the expression of key transcription factor and receptor molecules whose presence or absence help to specify the cell fate, or to activate or suppress a particular differentiation pathway. We study the structure, dynamics and evolution of transcription networks. |
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Identification and comparison of signaling and regulatory pathways that regulate cells' response to environmental stimuli. We integrate gene expression, genome sequence and epigenomic data from multiple species to discover essential regulatory pathways underlying fundamental biological processes such as aging and fat loss. |
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Stem cell differentiation We aim to discover novel regulatory genes and proteins that regulate the self-renewal or differentiation of embryonic stem cells, and then promote the efficiency of cellular reprogramming and guided differentiation. |
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Research support from NSF, NIDDK, NHLBI |
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