Yong-jie Xu

Biography

M.D.: Peking Union Medical College/Chinese Academy of Medical Sciences Ph.D.: Biochemistry, Cell and Molecular Biology Program, The Johns Hopkins University School of Medicine Postdoctoral: Memorial Sloan-Kettering Cancer Center

Research Interest

Understanding how genome integrity is maintained over generations – during which time the genome has to be accurately duplicated in each cell cycle – is one of the fundamental problems of modern biology. It is also a critical aspect of the more general problem of understanding the mechanisms that control cellular proliferation and prevent oncogenesis. The stability of the genome depends upon the precise operation of the DNA replication machinery and upon the checkpoint mechanism that deals with various perturbations of DNA replication. If undetected by the checkpoint, perturbed DNA replication forks become unstable and may undergo catastrophic collapse, leading to mutagenic chromosomal DNA damage or cell death. For this reason, defects in the DNA replication checkpoint are known causes of genome instability and cancer. The research interest of his lab is to understand the signaling mechanism of the replication checkpoint (also called the S phase checkpoint) when DNA replication is perturbed by various endogenous or exogenous factors. The checkpoint senses the perturbations and stimulates a series of coordinated protective cellular responses such as cell cycle delay, increased production of dNTPs, and protection of perturbed forks from collapsing so that DNA synthesis can resume when perturbations diminish. The long-term goal of their research is to understand how checkpoint signaling is initiated at perturbed forks and how perturbed forks are protected by activated checkpoint.  They use the fission yeast S. pombe as the primary model for this study because it is a well-established system for studying the cellular mechanisms that are conserved in humans. In addition, the checkpoint signaling pathways in fission yeast are relatively linear, which promotes unambiguous description of the signaling mechanism. They believe that progress in this study will advance our knowledge about how genome integrity is maintained and how it can be disrupted in human cells. It may also provide therapeutic benefits for cancer chemotherapy designed to interfere with DNA replication or the checkpoint signaling in tumor cells. Based on their recent unexpected genetic data, we are also working on the combination therapies that are based on the clinically used drug hydroxyurea. Hydroxyurea perturbes DNA replication and acitivates the replication checkpoint in all eukaryotic organisms. They hope that the drug combinations can be useful for the treatment of cancer or fungal infections.  His lab is located in room 156 and 158 and the office is in room 160, Biological Sciences Building-II.  They are currently recruiting talented graduate students and motivated post-doctoral fellows to join the lab and carry out the exciting research.