Laboratory of Zheng Fu, Ph.D.
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.
Shengzhe Shang, Ph.D.
Donghua Wen, Ph.D.
Youwei Zhang, Ph.D.
Wu J, Ivanov II, Fisher PB, Fu Z. PLK1 induces epithelial-to-mesenchymal transition and promotes epithelial cell motility by activating CRAF/ERK signaling. eLIFE, 2016.
Zhang J, Yuan C, Wu J, Elsayed Z, Fu Z. Polo-like kinase1-mediated phosphorylation of Forkhead box protein M1b antagonizes its SUMOylation and thereby facilitates its mitotic function. J Biological Chemistry. 2015, 290(6): 3708-3719.
Yuan C, Wang L, Zhou L, and Fu Z. The Function of FOXO1 in the late phases of the cell cycle is suppressed by PLK1-meddiated phosphorylation. Cell Cycle. 2014, 13(5): 807-819.
Zhang H., Wu J, Keller JM, Yeung K, Keller ET, Fu Z. Transcriptional regulation of RKIP expression by androgen in prostate cells. Cellular Physiology and Biochemistry. 2012, 30(6): 1340-1350.
Fu Z, Regan K, Zhang L, Muders MH, Thibodeau SN, Fench A, Wu Y, Kaufmann SH, Lingle WL, Chen J, Tindall DJ. Deficiencies in CHFR and MMR genes synergistically enhance tumor susceptibility in mice. Journal of Clinical Investigation. 2009, 119(9):2714-2724.
Fu Z, and Tindall DJ. FOXOs, cancer and regulation of apoptosis. Oncogene. 2009, 27:2312-2319.
Fu Z, Malureanu L, Huang J, Wang W, Li H, van Deursen JM, Tindall DJ, Chen J. Plk1-dependent phosphorylation of FoxM1 regulates a transcriptional program required for mitotic progression. Nature Cell Biology. 2008, 10(9):1076-1082.
Fu Z, Kitagawa Y, Shen R, Shah R, Mehra R, Rhodes D, Keller PJ, Mizokami A, Dunn RL, Chinnaiyan AM, Yao Z, and Keller ET. The metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. The Prostate. 2006, 66(3): 248-256.
Keller ET, Fu Z, and Brennan M. The biology of a prostate cancer metastasis suppressor protein: Raf kinase inhibitor protein. Journal of Cellular Biochemistry. 2005, 94: 273-278.
Zhang L, Fu Z, Binkley C, Logsdon C, and Simeone D. The role of RKIP in regulating ß-cell proliferation. Surgery. 2004, 136(3):708-715.
Keller ET, and Fu Z. Defining RKIP as a protein that regulates prostate cancer metastasis. The American Journal of Urology review. 2004, 2(2): 72-80.
Fu Z, Smith P, Zhang L, Rubin R, Dunn RL, Yao Z, and Keller ET. Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis. Journal of the National Cancer Institute. 2003, 95(2):878-889.
Kanolkar A, Fu Z, Underwood LJ, Bondurant KL, Rochford R, and Cannon MJ. CD4+ T cells-induced differentiation of EBV-transformed lymphoblastoid cells is associated with diminished recognition by EBV-specific CD8+ cytotoxic T cells. Journal Immunology. 2003, 170(6):3187-3194.
Fu Z, Dozmorov IM, and Keller ET. Osteoblasts produce soluble factors that induce a gene expression pattern in non-metastatic prostate cancer cells similar to that found in bone metastatic prostate cancer cells. The Prostate. 2002, 51:0-20.
Zhang J, Dai J, Qi Y, Lin D, Smith P, Strayhorn C, Mizokami A, Fu Z, Westman J, and Keller ET. Osteoprotegerin inhibits prostate cancer-induced osteoclastogenesis and prevents prostate tumor growth in the bone. J Clinical Investigation. 2001, 107(10): 1235-1243.
Fu Z, and Cannon MJ. Functional analysis of the CD4+ T cell response to Epstein-Barr virus: T cell-mediated bystander activation of resting B cells and induction of BZLF1 expression by a gp39-CD40-dependent pathway. Journal Virolology. 2000, 74: 6675-6679.