Yanchang Wang, Ph.D. Associate Professor of Cell Biology Department of Biomedical Sciences College of Medicine, Florida State University 1115 West Call Street Tallahassee, FL 32306-4300 Office: (850) 644-0402 Lab: (850) 645-2926 Dr. Wang's Faculty Profile
Research Interests
Yeast Cell Cycle Regulation The regulation of mitotic exit in budding yeast The key driving force of cell division is cyclin dependent kinase (CDK), a protein kinase conserved in all eukaryotic cells. Its activity is high during S and M phase as active CDK is required for DNA synthesis and chromosome segregation. After chromosome segregation, two signal transduction pathway, named FEAR (Cdc14 early anaphase release) and MEN (mitotic exit network), are responsible for the inactivation of CDK by activating a phosphatase Cdc14. We are currently investigating how the components in FEAR and MEN pathways regulate Cdc14 activity and also interested in addressing the role of Cdc14 in anaphase progression. Dissection the molecular process of the spindle-kinetochore interaction Although more than 60 kinetochore proteins have been identified, there are several key questions remains answered. First, it is not clear whether the same kinetochore proteins are responsible for the initial chromosome capture as well as the stable chromosome-microtubule interaction. Moreover, the molecular mechanism that controls the transition from the initial capture to a stable chromosome-microtubule interaction remains unclear. We are currently investing the function of some proteins required for the establishment of stable kinetochore-microtubule interaction. Chromosome morphogenesis and cell cycle progression In eukaryotic cells, DNA cycle includes DNA duplication, nucleosome assembly, chromatin modification, and the establishment of cohesion and condensation. Entry into mitosis before chromosome maturation could be a disaster as the maturation facilitates chromosome attachment. The presence of a feedback mechanism that prevents mitotic entry when chromosomes are immature will benefit faithful chromosome segregation. We found that stressful DNA synthesis stabilized Swe1, the inhibitory kinase for CDK. We will use budding yeast to study the connection between DNA replicatoin and Swe1 degradation. Systematic screen for inhibitors of the yeast essential gene products Budding yeast is a valuable model organism to study the basic cellular processes that are conserved from yeast to human. Meanwhile, many aspects of yeast cell structure and life cycle are unique. Since the completion of yeast genome sequence, genome wide studies have greatly advanced our understanding of the function of each yeast gene. As the ultimate goal of biomedical research is to cure human diseases, we will use yeast as the model organism to identify inhibitors for all the proteins that are essential for cell growth. The inhibitors could be used for the human diseases treatment or biomedical research and they could inactivate the human homologues. On the other hand, the inhibitors for the yeast-specific genes have great potential for the treatment of fungal infections.
Current Projects
To understand the molecular function of Cdc5 in FEAR activation. To investigate the role of Cdc14 release in anaphase progression. To understand how the stable kinetochore-microtubule interaction is established. To study how cell cycle machinery responds to stressful DNA replication.
Current Laboratory Members
Postdoctoral fellow: Graduate Student: Fengshan Liang Ph.D.: Chinese Academy of Sciences Fengzhi Jin Ph.D.: Beijing Normal University Visiting Scholar: Dr. Xuemei Tian Jinsong Wu B.S.: Sichuan University Daniel Richmond B.S.: Florida State University Kelly McKnight B.S.: Florida State University
Selected References
Wang Y*, Hu F*, Elledge SJ. (2000) The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit. Curr Biol. 10:1379-82. (* equal contributor)   Hu F*, Wang Y*, Liu D, Li Y, Qin J, Elledge SJ. (2001) Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell. 107:655-65. (* equal contributor)   Wang Y, Shirogane T, Liu D, Harper JW, Elledge SJ. (2003) Exit from exit: resetting the cell cycle through Amn1 inhibition of G-protein signaling. Cell 112:697-709   Wang Y. and Ng T. (2006) Phosphatase 2A negatively regulates mitotic exit in Saccharomyces cerevisiae. Mol. Biol Cell 17:80-89   Liu H. and Wang Y. (2006) The Function and Regulation of Budding Yeast Swe1 in Response to Interrupted DNA Synthesis. Mol Biol Cell. 17:2746-56   Tang X. and Wang Y. (2006) Pds1/Esp1 dependent and independent sister chromatid separation in mutants defective for protein phosphatase 2A. Proc Natl Acad Sci U S A. 103:16290-16295   Jin F. and Wang Y. (2006) Budding yeast DNA damage adaptation mutants exhibit defects in mitotic exit. Cell Cycle 5:2914-9   Liang F. and Wang Y. (2007) DNA damage checkpoints inhibit mitotic exit by two different pathways. Mol. and Cell. Biol. 14:5067-5078 Li Y., Liang F., Jiang W., Yu F., Cao R., Ma Q., Dai X., Jiang J., Wang Y*., and Si S*. (2007) DH334, a Beta-carboline anti-cancer drug, inhibits the CDK activity of budding yeast. Cancer Biology and Therapy 6:1193-1199 * co-corresponding author   Da-Hua Fu1*, Wei Jiang1*, Jian-Ting Zheng2, Gui-Yu Zhao1, Yan Li1, Hong Yi1, Zhuo-Rong Li1, Jian-Dong Jiang1, Ke-Qian Yang2§, Yanchang Wang3§, and Shu-Yi Si1§ (2008) Jadomycin B, an Aurora-B kinase inhibitor discovered through virtual screening. Molecular Cancer and Therapeutics 7:2386-2393. §Co-corresponding author.   Fengzhi Jin, Hong Liu, Fengshan Liang, Raed Rizkallah, Myra M. Hurt and Yanchang Wang (2008) Temporal control of the dephosphorylation of Cdk substrates by mitotic exit pathways in budding yeast. Proc Natl Acad Sci U S A. 105:16177-82   Hong Liu, Fengshan Liang, Fengzhi Jin and Yanchang Wang. (2008) The coordination of centromere replication, spindle formation and kinetochore-microtubule interaction in budding yeast. PLoS Genetics. Nov.4:e1000262. Epub 2008 Nov 21.   Fengzhi Jin, Daniel Richmond, and Yanchang Wang (2009). The multiple-layer regulation of metaphase-to-anaphase transition. Cell Cycle 8:700-704.   Fengshan Liang, Fengzhi Jin, Hong Liu and Yanchang Wang. (2009) The molecular function of the yeast polo-like kinase Cdc5 in Cdc14 release during early anaphase. Mol. Biol Cell 20:3671-3679