Chen Fei (Xavier)
Fei (Xavier) Chen, Ph.D.
PhD: Northwestern University Feinberg School of Medicine (2018)
MS: Fudan University (2012)
BS: Shandong University (2009)
Postdoctoral fellow: Memorial Sloan Kettering Cancer Center (2018-2019)
Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 Tel: +86 18049996860
Email: feixchen@fudan.edu.cn
Lab homepage: https://chenf-lab.fudan.edu.cn/
Fei (Xavier) Chen, Ph.D., is a Principal Investigator of the Institute of Biomedical Sciences (IBS) and Shanghai Cancer Center at Fudan University.
Fei received his BS degree from Shandong University in 2009. After graduation, Fei joined Dr. Yanhui Xu’s laboratory at Fudan University and completed the master's training, where he focused on elucidating the structures and functions of epigenetic modifiers. In collaboration with Dr. Yujiang Shi at Harvard, he found that histone demethylase LSD2 is catalytically induced by a cofactor and demonstrated the molecular mechanisms, thus establishing a new model for the regulation of histone modifiers by cofactors (Molecular Cell, 2013; Cell Research 2013). These findings aroused his interests in chromatin biology, epigenetic modifications, and how regulatory signals are interpreted by the transcription machinery.
Therefore, Fei joined the laboratory of Dr. Ali Shilatifard, a leader in the field of epigenetics, to complete his Ph.D. thesis focusing on understanding the molecular mechanisms of transcriptional regulation. During this time, he identified transcription regulator PAF1 as a crucial player in multiple steps of transcription especially the pausing-elongation transition, a rate-limiting step for transcription activation (Cell, 2015; Genes & Development 2015). Moreover, he revealed the mechanisms underlying the roles of enhancer activation during the dynamic change of transcription, providing novel insights into the functions of cis-regulatory elements in gene expression (Science, 2017).
Aiming to apply his knowledge in transcription and epigenetics to tackle problems in human diseases such as cancer, Fei decided to extend his training by working as a postdoctoral fellow in the laboratory of Dr. Joan Massague, a pioneer in the field of cancer metastasis, at Memorial Sloan Kettering Cancer Center. During that time, he has obtained extensive knowledge and exceptional training in cancer biology with a focus on the roles of transcriptional and epigenetic dysregulation in cancer progression (Cancer Discovery, 2020).
In 2019, Fei took the faculty position at Fudan University in Shanghai and established a research laboratory aiming to elucidate the fundamental mechanisms of transcriptional and epigenetic regulation and the contribution of their dysregulation to disease, especially cancer. Since then, collaborating with Dr. Yanhui Xu, they have identified a new transcription regulator composed of Integrator and PP2A-AC (INTAC) and unraveled its function in controlling early elongation (Science, 2020). Moreover, by utilizing vigorous biochemistry and multi-omics approaches, the team has recently discovered how the axis of INTAC-P-TEFb controls the dynamic phosphorylation of SPT5, a critical regulation of transcriptional pausing and elongation, to orchestrate the progression of the transcription machinery (Molecular Cell, 2021). Together with the team, Fei aims to pursue interdisciplinary studies by using different approaches in biochemistry, bioinformatics, genetics and epigenetics, functional genomics, and cancer biology, with the ultimate goal to make impactful discoveries and benefit patients and the community.
Transcription, epigenetics and chromatin
Transcriptional and epigenetic dysregulation in disease
The research goal of our lab is to elucidate fundamental mechanisms of transcriptional and epigenetic regulation and the roles of their dysregulation in disease, especially cancer.
Transcription is an elaborate, multistep process that involves a diverse network of transcriptional machinery decoding the genetic and epigenetic information stored in chromatin. As such, miscommunication between transcriptional machinery and chromatin can induce transcriptional deregulation that perturbs physiological functions and, when accumulated to a certain extent, causes disease including cancer. Whole-genome sequencing studies have identified human cancers to harbor frequent mutations of transcription factors, transcriptional signaling pathways and epigenetic regulators, highlighting the implication of transcriptional and epigenetic dysregulation in cancer. In our lab, we strive to understand what are the principles of communication between transcriptional machinery and chromatin, why the deregulation of transcriptional regulators can alter gene expression, and how to intervene and rectify this miscommunication to alleviate or even cure disease. We aim to pursue interdisciplinary studies by using different approaches in biochemistry, bioinformatics, genetics and epigenetics, functional genomics, and cancer biology, with the ultimate goal to make impactful discoveries and benefit patients and the community. The specific research directions of our lab include:
1) Molecular mechanisms of transcriptional and epigenetic regulation.
2) Development of patient sample-based high-throughput techniques in transcription and epigenetics.
3) Integrated transcriptomic and epigenomic profiling and bioinformatic analyses in patient samples to discover disease etiology and treatment strategies.
4) Integrated single-cell RNA sequencing and spatial transcriptome analyses to decipher mechanisms of cancer metastasis.
5) CRISPR screens to discover novel regulators in transcription, epigenetics, and cancer.
Song A and Chen FX*. The pleiotropic roles of SPT5 in transcription. Transcription. 2022 Jul 25;1-17. doi: 10.1080/21541264.2022.2103366.
Wang X#, Qi Y#, Wang Z#, Wang L, Song A, Tao B, Li J, Zhao D, Zhang H, Jin Q, Jiang YZ, Chen FX*, Xu Y*, Chen X*. RPAP2 regulates a transcription initiation checkpoint by inhibiting assembly of pre-initiation complex. Cell Reports. 2022 Apr 26;39(4):110732.
Wang Z#, Song A#, Xu H#, Hu S, Tao B, Peng L, Wang J, Li J, Yu J, Wang L, Li Z, Chen X, Wang M, Chi Y, Wu J, Xu Y, Zheng H, Chen FX*. Coordinated regulation of RNA polymerase II pausing and elongation progression by PAF1. Science Advances. 2022 Apr;8(13):eabm5504.
Hu S#, Peng L#, Xu C#, Wang Z, Song A, and Chen FX*. SPT5 stabilizes RNA polymerase II, orchestrates transcription cycles, and maintains the enhancer landscape. Molecular Cell. 2021 Nov 4;81(21):4425-4439.e6.
Zheng H#, Qi Y#, Hu S#, Cao X#, Xu C#, Yin Z, Chen X, Li Y, Liu W, Li J, Wang J, Wei G, Liang K, Chen FX*, Xu Y*.(2020) Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase. Science. 2020 Nov 27;370(6520):eabb5872.
