教育背景

1997-2001 美国杜克大学生物学 学士

2003-2011 美国哥伦比亚大学生物学 博士

工作经历

2001-2003 美国哈佛大学医学院 技术员

2011-2017 美国纪念斯隆-凯特琳癌症中心 博士后

2017-2021 清华大学医学院 助理教授 

2021-2024 清华大学医学院 副教授 

2024-至今 清华大学基础医学院 副教授

研究领域

癌症发生过程与基因调控。致癌基因通过激活细胞中特定基因的转录来促进肿瘤的发生与发展。基于此，本实验室研究内容如下：1）研究癌细胞中异常激活的转录网络的起源，以及致癌基因对这些异常激活的转录网络的调控作用；2）研究肿瘤发展过程中异常激活的转录网络的变化情况，以及肿瘤抑制基因在这些异常激活的转录网络变化过程的抑制作用；3）以癌症中异常激活的基因转录网络为基础，研究肿瘤发展过程中免疫逃逸与代谢情况的变化。

科学贡献

早期利用Adeno-associated Virus (AAV)和 CRISPR/Cas9系统，成功开发出一套便捷的自发胰腺癌小鼠模型；揭示在受损伤的小鼠胰腺中，存在着一群能够促进胰腺恢复的前体细胞；阐明胰腺癌进展中Kras突变体促进转录激活的分子机制；通过这些创新性成果，以胰腺癌为模型为研究癌症发生过程的关键分子机理与基因调控提供新的理论依据与方法，鉴定与寻找治疗胰腺癌潜在的药物靶点。迄今在包括Nature、Cell在内的国际期刊上发表学术论文17篇，总引用5000次左右。

荣誉奖励

2018 国家级青年人才项目

2017 纪念斯隆凯特琳博士后研究员奖

2017 NIH K22 Award

2010 John S.Newberry Award (Columbia University)

代表性论文

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.