Fei (Xavier) Chen
Investigator
The Institute of Biomedical Sciences (IBS) & Shanghai Cancer Center
Fudan University, Shanghai. 200032
Email: feixchen@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. 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). By utilizing vigorous biochemistry and multi-omics approaches, the team has 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). Moreover, they have revealed that the recruitment of INTAC at promoters is influenced by PAF1, which explains the role of PAF1 in early elongation control (Science Advances, 2022). The team also have dissected the differential control of transcription and gene expression by INTAC’s two catalytic activities—The RNA endonuclease and protein phosphatase (Molecular Cell, 2023). Recently, they have identified a stable association of INTAC with ssDNA-binding complex SOSS. Via SSB1-mediated ssDNA recognition, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates paused Pol II-associated R-loops to prevent R-loop-induced genome instability (Nature, 2023). 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.
