Education:
1997-2001 B.Sc. in Biology, Duke University, Durham, USA
2003-2011 Ph.D. in Biology, Columbia University, New York, USA
Professional Positions:
2001-2003 Technician, Harvard medical school, Boston, USA
2011-2017 Postdoctoral Research Fellow, Memorial Sloan Kettering Cancer Center, New York, USA
2017-2021 Assistant Professor, School of Medicine, Tsinghua University, Beijing, China
2021-2024 Associate Professor, School of Medicine, Tsinghua University, Beijing, China
2024-now Associate Professor, School of Basic Medical Sciences, Tsinghua University, Beijing, China
Research Areas:
Oncogenes promote tumorigenesis through transcriptional control. With this concept as a basis, some goals of our laboratory are:1) To identify the origins of oncogenic transcriptional programs in cancer, and to understand the mechanisms by which they come under oncogene control.2) To understand how oncogenic transcriptional programs evolve during tumor progression, and to understand the role of tumor suppressors in restraining these changes.3) To use tumorigenic transcriptional programs as a window into important areas of tumor biology, including immune evasion and metabolism.
We pioneered the use of adeno-associated virus (AAV) and the CRISPR/Cas9 to create flexible systems for the examination of gene function directly in pancreatic cancer. Using these mouse models, we demonstrated the existence of a progenitor cell for pancreatic cancer which express a proto-oncogenic transcriptional program driven and sustained by oncogenic mutant KRAS. We also identify a wound-like program that drives malignant conversion of pancreatic cancer cells. Through these innovative findings, new theoretical foundations and methods have been provided for studying the key molecular mechanisms and gene regulation during cancer development. The research has sought potential drug targets for the treatment of pancreatic cancer. To date, 17 academic papers have been published in international journals, including Nature and Cell, with a total of approximately 5,000 citations.
Honors and Awards:
Ø 2018 Youth Thousand Talent award
Ø 2017 Postdoctoral Researcher Award, MSKCC
Ø 2011-2013 Translational Research in Oncology Training Program, MSKCC
Ø 2011 John S. Newberry Award (Outstanding Biology Graduate), Columbia University
Ø 2005-2007 NIH Training Grant, Columbia University
Ø 2001 Excellence in Plant Science Prize, Duke University
Selected Publications:
1.Baldan J#*, Camacho-Roda J#, Ballester M#, Hoj K, Kurilla A, Maurer H, Arcila-Barrera S, Lin X, Pan Z, Castro J, Guiliani A, Rift C, Hasselby J, Bouwens L, Lefebvre V, David C, Parnas O, Kathleen E, Janine R, Arnes Luis* (2024) Resolution of Acinar Dedifferentiation Regulates Tissue Remodeling in Pancreatic Injury and Cancer Initiation. Gastroenterology. (#equal contribution)
2.Liu X#, Liu X#, Du Y#, Zou D, Tian C, Li Y, Lan X, David C, Sun Q, Chen M*(2023) Aberrant accumulation of Kras-dependent enhancer RNAs and PROMPTs during tumor progression renders cancer cells susceptible to PAF1 depletion. Cell Reports 42,112979.
3.Zhuo M*, Mao J, David C* (2023) Protocol to package and concentrate adeno-associated virus serotype 8 for use in autochthonous mouse models of pancreatic cancer. STAR protocols 4 (1), 102108.
4.Liu X#, Guo Z#, Han J#, Peng B, Zhang B, Li H, Hu X, David C, Chen M*(2022) The PAF1 complex promotes 3’ processing of pervasive transcripts. Cell Reports 38,110519.
5.Meng J, Zhao S, Tao Y, Zhang T, Wang X, Zhang Y, Sun K, Yuan M, Chen J, Wei Y, Lan X, Chen M*, David C, Chang Z, Guo X, Pan D, Chen M, Shao Z*, Kang Y*, Zheng H* (2022) Tumor-derived Jagged1 promotes cancer progression through immune evasion. Cell Reports38, 110492.
6.Li Y#, He Y#, Peng J#, Li Z, Zhang B, Ma J, Zhuo M, Zou D, Liu X, 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 C* (2021) Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer. Nature Cancer 2:49-65. (#equal contribution)
7.Su J , Morgani S, David C, Wang Q ,Er E, Huang Y, Basnet H , Zou Y, Shu W,Soni R, Hendrickson R, Hadjantonakis A, Massague J* (2020) TGF-β orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1.Nature 577(7791)566-571.
8.Huang Y, Hu J, Chen, F, Lecomte N, Basnet H, David C, Witkin M, Allen P, Leach S, Hollmann T, Iacobuzio-Donahue C, Massague J* (2020) ID1 mediates escape from TGFβ tumor suppression in pancreatic cancer. Cancer discovery 10 (1), 142-157.
9.David C#, Massague J#* (2018) Contextual determinants of TGFβ action in development, immunity and cancer. Nature reviews Molecular cell biology 19 (7):419-435.
10.David C, Huang Y, Chen M, Su J, Zou Y, Bardeesy N, Iacobuzio-Donahue CA, Massague J* (2016) TGF-β Tumor Suppression Through A Lethal EMT. Cell 164:1015-30.
11.Chen M, David C, Manley J* (2012) Concentration-dependent control of pyruvate kinase M mutually exclusive splicing by hnRNP proteins. Nat Struct Mol Biol 19:346-54.
12.David C, Manley J* (2011) The RNA polymerase C-terminal domain: a new role in spliceosome assembly. Transcription 2 (5), 221-225.
13.Kashima T, Rao N, David C, Manley J* (2011)The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65–Prp19 complex. Genes & development 25 (9):972-983.
14.Chen M, David C, Manley J* (2010) Tumor metabolism: hnRNP proteins get in on the act. Cell Cycle 9: 1863-1864.
15.David C#, Chen M#, Assanah M, Canoll P, Manley J* (2010) HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature 463: 364-8. (#equal contribution)
16.David C, Manley J* (2008) The search for alternative splicing regulators: new approaches offer a path to a splicing code. Genes & development 22 (3), 279-285.
17.Kashima T*, Rao N, David C, Manley J* (2007) hnRNP A1 functions with specificity in repression of SMN2 exon 7 splicing. Human molecular genetics16(24):3149-3159.
