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Charles David

Charles David

 

Office/Lab TEL: 010-62771156

E-mailcdavid@mail.tsinghua.edu

 

Research Area:

 

Cancer Biology  

 

The David laboratory examines essential transcriptional networks in cancer, and the connections of these networks to oncogenic signaling pathways. Targeting the transcriptional drivers of cancer has provided one of the most successful targeted therapies in oncology, tamoxifen, which targets the estrogen receptor, a lineage determining transcription factor. Unfortunately, in contrast to breast cancer, the transcriptional drivers of most cancer types are unknown. My lab employs functional approaches in mouse models to identify the transcriptional drivers of other tumor types, and to characterize the networks they form. One observation we have made is that many essential transcription factors in cancer are derived from normal stem or progenitor cells in the tissues from which the tumors arise. We have found that oncogenic signals interact with these stem cell-derived networks in specific ways that drive and sustain tumorigenesis. Understanding these specific connections is a major interest of the laboratory. In addition to our interest in transcriptional regulation per se, we have also begun to harness the genes downstream of essential transcription factors to identify novel in vivo tumor dependencies that cannot be identified through in vitro genome-wide screens.

 

Selected Publications:

· David CJ, Huang YH, Chen M, Su J, Bardeesy N, Iacobuzio-Donahue CA, Massagué J (2016) TGF-β tumor suppression through a lethal EMT. Cell 164(5):1015-30.

· Chen M, David CJ, Manley JL (2012). Concentration-dependent control of mutually exclusive pyruvate kinase M splicing by hnRNP proteins. Nature Structural and Molecular Biology

· David CJ, Boyne AB, Millhouse SR, Manley JL (2011). The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65-Prp19 complex. Genes and Development 25: 972-83.

· David CJ, Manley JL (2010). Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhinged. Genes and Development 24: 2324-64.

· David CJ, Chen M, Assanah M, Canoll P, Manley JL (2010). HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 463: 364-8.

· David CJ, Manley JL (2008). The search for alternative splicing regulators: new approaches offer a path to a splicing code. Genes and Development 22: 279-85.


 

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