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Institute of Molecular Medicine

Laboratory of Zheng Fu, Ph.D.

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Research projects

The research programs in Dr. Fu’s laboratory focus on elucidating the molecular mechanisms of the control of the cell cycle and maintenance of genomic stability, understanding how misregulation of those physiological processes contribute to carcinogenesis and applying the findings to develop novel and targeted cancer therapies as an improved way of preventing and treating cancers.

During the cell division cycle, mitotic entry, spindle assembly, chromosome segregation and cytokinesis must all be carefully coordinated to ensure that the two daughter cells inherit all the genetic material required for further growth and development. When this process is disrupted, it can lead to a number of diseases, such as cancer.

Central to this coordination are several prominent protein kinases including Polo-like kinase 1 (PLK1), a serine/threonine protein kinase. A major area of interest to this group involves mechanistically understanding the regulatory function of PLK1 in mitosis and how deregulation of PLK1 contributes to carcinogenesis.

By using yeast two-hybrid screening and tandem affinity purification (TAP) combined with mass spectrometry analysis, researchers have identified several novel PLK1-interacting proteins including FoxM1. The laboratory’s current focus is on exploring working mechanisms by which those proteins are involved in PLK1 function and/or regulation and by which deregulation of PLK1 contributes to tumorigenesis by using loss-of-function and gain-of-function strategies in cell cultures and in animal models.

Another research focus of the lab is on characterizing the function and regulation of CHFR, a mitotic checkpoint, during mitosis and tumor suppression. Laboratory members are also keenly interested in translating their discoveries from basic cancer studies to experimental therapeutics.

Laboratory members

Donghua Wen, Ph.D.
Postdoctoral Fellow

Kevin Corapi
Lab Technician

 

Xiaoyan Hu, Ph.D.
Postdoctoral Fellow

Lilia Gheghiani, Ph.D.
Postdoctoral Fellow

Key publications

Wen, D., Wu, J., Wang, L., Fu, Z. 2017. SUMOylation promotes nuclear import and stabilization of polo-like kinase 1 to support it mitotic function. Cell Reports. 21(8): 2147-2159. PMID: 29166606.

Fu, Z., Wen, D. 2017. The emerging role of polo-like kinase 1 in epithelial-mesenchymal transition and tumor metastasis. Cancers. 9(10): 131. PMID: 28953239.

Wu, J., Ivanov, I.I., Fisher. P.B., Fu, Z. 2016. PLK1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling. eLIFE. 5: e10734. PMID: 27003818. (Collaborated with Drs Andrei Ivanov and Paul Fisher)

Zhang, J., Yuan, C., Wu, J., Elsayed, Z., Fu, Z. 2015. Polo-like kinase1-mediated   phosphorylation of Forkhead box protein M1b antagonizes its SUMOylation and thereby facilitates its mitotic function. Journal of Biological Chemistry. 290(6): 3708-3719. PMID: 25533473.

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