Li Hoi Yeung
Assistant Chair (Academic)
Telephone: 6316 2931
- B.Sc. The Hong Kong Polytechnic University, Hong Kong
- Ph.D. The Chinese University of Hong Kong, Hong Kong
- Sep 2010 - Present
Associate Professor, School of Biological Sciences, Nanyang Technological University, Singapore
- Dec 2004 - Sep 2010
Assistant Professor, School of Biological Sciences, Nanyang Technological University, Singapore
- Aug 2000 - Dec 2004
Postdoctoral Fellow, Howard Hughes Medical Institute, Carnegie Institution of Washington, Baltimore, USA
In animal cells, the transition from interphase to mitosis is accompanied by dramatic changes in cellular architecture such as nuclear envelope break down, chromosome condensation and spindle assembly. Proper spindle assembly is crucial to maintain the genetic stability of the cell. Defects in spindle assembly often lead to aneuploidy, chromosomes mis-segregation, cellular abnormalities or mitotic cell death.
It is believed that the presence of RanGTP gradient on the mitotic chromosomes and the activity of RCC1 play essential roles in regulating mitotic spindle assembly. Using advanced microscopy techniques and computational modeling, we found that the interaction between RCC1 and mitotic chromosomes stimulates RanGTP gradient production, which in turn activates spindle assembly factors to organize mitotic spindle. Furthermore, we proved that the phosphorylation state of RCC1 is mediated by the master mitotic regulator, cdc2 kinase, thus modulating RCC1’s activity and the formation of spindle during mitosis. Using computational modeling, we concluded that the spatial arrangement of mitotic chromosomes provided additional driving force for the establishment of the RanGTP gradient. Although much is known about function of RanGTP in regulating mitotic spindle, the role of RanGTP towards other mitotic events have not been explored. Therefore, we are now elucidating various cellular division events from the perspective of RanGTP-dependent processes.
The Kinesin motors are a conserved class of microtubule-dependent molecular motor proteins. Apart from transportation of macromoleculars within a cell via the microtubules network, kinesin motors also play important roles in mitotic progression. Although it has been showed that Chromokinesin KIF4A, Eg5, Kid, are essential regulators in various stages of mitosis, there are a lot of pressing ambiguities that needs to be addressed. We are interested in understanding how post-translational modifications could influence the functions of these mitotic kinesin motors from the aspect of structural and cell biology.
Aberrant mitosis will lead to prolonged mitotic arrest and subsequent mitotic cell death. Therefore, targeting the mitotic machinery in anti-cancer treatments is an effective way to eliminate rapidly dividing cancer cells. We have identified that DNA damaging agent, actinomycin D, induced mitotic cell death by inhibiting a number of chromosomal mitotic regulators. Recently, We found that caspases are activated during mitotic arrest and caspases-3 cleaved Cap-H, a subunit of condensin I. This alters the chromosome integrity and allows chromosomal DNA fragmentation by caspase-activated deoxyribonucleases. These findings suggest an important link between activation of caspases and the loss of chromosomal structure integrity via the regulation of condensin I, which provide fundamental insights into a major cell death process during cancer treatment. Although mitotic cell death based cancer treatment is effective for some patients, others show little improvement and instead develop resistance to it. The cause of response heterogeneity among different cancers remains uncertain. In this project, we seek to identify the cause of the response heterogeneity of different cancer cell types towards different mitotic cell death based cancer therapy.