Identifyingepigenetic vulnerabilities of cancer cells and dissecting their molecular mechanism
The main focus of Chen lab is to elucidate the mechanism by which epigenetic regulators regulate tumorigenesis through dictating a cancer-specific transcriptional program.Ourlab combines cutting edge genomic technologies, biochemical specialties, molecular biology methods and in vivo mouse models to study frontier questions in cancer biology. We are also interested in fundamental questions in RNA biology: how is RNA transcribed from genes, what re the differences between non-coding RNA and what are the underlying molecular mechanisms. The main interests of our lab include the following aspects:
1.Identify key chromatin factors that remodel chromatin changes during pancreatitis and pancreatic cancer initiation, and elucidate their working mechanism.
2.Develop novel in vivo CRISPR-Cas9 screening method to identify key epigenetic factors and RNA binding proteins that are critical for pancreatic tumorigenesis in vivo.
3.Elucidate the working mechanism of general dependency of leukemia cells on JMJD1C.
4.Examine regulation mechanism on mRNA transcription initiation, elongation and termination; identify differential regulatory mechanisms that distinguish non-coding RNA from mRNA.
•Li Y, He Y., Peng J, Su Z, Li Z, Zhang B, Ma J, Zhuo M, Zou D, Liu X, Wang W, Huang D, Xu M, Wang J, Deng H, Xue J, Xie W, Lan X,Chen M, Zhao Y, Wu W and David CJ. Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer. Nature Cancer. 2021 2: 49–65
•David CJ, Huang Y,Chen M, Su J, Zou Y, Bardeesy N, Iacobuzio-Donahue CA, Massagué J.TGF-β Tumor Suppression Through A Lethal EMT. Cell. 2016 Feb 25;164(5):1015-30.
•Zhu N,Chen M, Eng R, Sinha AU, Rahnamay NF, Koche R, Al-Shahrour F, Minehart JC, Chen CW, Deshpande AJ, Xu H, S. Chu H, Ebert BL, Roeder RG, Armstrong SA. Jmjd1c is required for MLL-AF9 and HOXA9 Mediated AML Stem Cell Self-Renewal. J Clin Invest. 2016 Mar 1;126(3):997-1011.
•Chen M, Zhu N, Liu X, Laurent B, Tang Z, Eng R, Shi Y, Armstrong SA, Roeder RG. JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors. Genes Dev. 2015 Oct 15;29(20):2123-39.
•Chen M, David CJ, Manley JL(2012).Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins.Nat Struct Mol Biol.19(3):346-54.
•David CJ#,Chen M#,Assanah M, Canoll P, Manley JL (2010) HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.Nature463: 364-8. * These authors contributed equally to this work.
•Chen M,Manley JL (2009). Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches.Nat Rev Mol Cell Biol.10(11):741-54.
•Feng Y,Chen M, Manley JL (2008). Phosphorylation switches the general splicing repressor SRp38 to a sequence-specific activator.Nat Struct Mol Biol.15(10):1040-8.
