

Visit
2024
Sir Tim Hunt, FRS
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A delightful lunch gathering with Nobel Prize winner Prof Tim Hunt with our lab.

Conferences
2024
Presentations at meetings this summer & winter.
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Choi HF and Poon RYC. Telomere function and evolution in heath and disease. 6-11 May. Rome, Italy.
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Lau TTY, Kim S, and Poon RYC. Dynamic kinetochore. 17-20 Jun. Caux, Switzerland.
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Kim S, Lau TTY, and Poon RYC. Dynamic kinetochore. 17-20 Jun. Caux, Switzerland.
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Yeung WTK and Poon RYC. InterU Symposium. 15 Jul. Hong Kong.
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Hsiu ON and Poon RYC. InterU Symposium. 15 Jul. Hong Kong.
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Poon RYC. Cell Organization and Genome Integrity. 7-9 Dec. Guangzhou.

Paper
2024
Sehong Kim et al. published a study detailing the functions and regulation of NDC80C, a complex pivotal in linking chromosomes to spindle poles during mitosis. The study also explored the potential of NDC80C as an anti-cancer drug target.
Kim S, Lau TTY, Liao MK, Ma HT, and Poon RYC (2024) Co-regulation of NDC80 complex subunits determines the fidelity of the spindle-assembly checkpoint and mitosis. Mol Cancer Res 22: 423-39.

Paper
2024
Dickson Yu et al. demonstrated the overarching role of BCL-XL in the timing of cell death during mitotic arrest. However, we found that modulation of BCL-XL can lead to compensatory changes in other anti-apoptotic proteins to regulate mitotic cell death.
Yu CY, Yeung TK, Fu WK, and Poon RYC (2024) BCL-XL regulates the timing of apoptosis independently of BCL2 and MCL1 compensation. Cell Death & Disease 15: 2.

People
2023
Dr. Yang Wang and Dr. Rita Ng took up postdoctoral positions at the University of Hong Kong.
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Dickson Yu and David Tam are continuing their PhD study at the University Hong Kong, while Peter Fu is continuing PhD study at the University of Tokyo.

Resources
2023
Wendy Yeung developed a pair of independently controlled molecular switches, enabling the toggling between two genes with comparable kinetics and tightness. This platform facilitates efficient generation of cell lines containing a two-gene switch that can be flipped within a fraction of the time of a cell cycle.
Yeung TK, Kim S, Ma HT, and Poon RYC (2023) A robust dual gene ON-OFF toggle directed by two independent promoter–degron pairs. J. Cell Sci. 136: jcs260754.

Paper
2023
Cyclin A and CDC25A are both activators of cyclin-dependent kinases (CDKs). Using a system that allows rapid degradation of cyclin A, Rita Ng uncovered an inverse relationship between the two CDK activators. Our results provide evidence of a compensatory mechanism involving CDC25A that ensures timely mitotic entry at different levels of cyclin A.
Ng LY, Ma HT, and Poon RYC (2023) Cyclin A–CDK1 suppresses the expression of the CDK1 activator CDC25A to safeguard timely mitotic entry. J. Biol. Chem. 299: 102957.

Seminar
2023
Peter Sicinski (Professor of Genetics, Harvard Medical School).
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Our lab's first invited seminar speaker since the pandemic!
A novel mechanism of G1/S transition revealed by targeted protein degradation in vivo.
1 March 2023, LTC.

Paper
2022
Inducing mitotic cell death is a cornerstone in cancer therapies. Why some cells undergo mitotic cell death and others not remains mysterious. Yang Wang deciphered the role of a mitochondrial ubiquitin ligase MARCH5 in mitotic cell death through MCL1-dependent and independent mechanisms.
Wang Y and Poon RYC (2022) MARCH5 regulates mitotic apoptosis through MCL1-dependent and independent mechanisms. Cell Death Differ 30: 753-65.

Research Projects
2022
Randy YC Poon was awarded a RGC GRF grant to study centrosome clustering in cells that failed to divide properly.
Life comes in clusters – comprehensive analysis of mitotic kinesins in centrosome clustering after tetraploidization

People
2021
Ken Ma took up an Assistant Professor position at the University of Hong Kong. Many congratulations.
Other people moving this summer include Adrijana Crncec (to NIH) and Preston Chu (to HKU).
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Paper
2021
The presence of a single CDK in yeast and multiple CDKs in higher eukaryotes have continued to intrigue the cell cycle field. Lau et al. showed that the classic mitotic CDK1’s functions can be replaced by CDK2 in human cell lines, suggesting that the difference between CDKs in human cells may be primarily quantitative rather than qualitative.
Lau HW, Ma HT, Yeung TK, Tam MY, Zheng D, Chu SK, and Poon RYC (2021) Quantitative differences between cyclin-dependent kinases underlie the unique functions of CDK1 in human cells. Cell Reports 37: 109808.

Resources
2021
Wendy Yeung made a series of Sleeping Beauty-based vectors for one-step generation of conditional KO of multiple genes in mammalian cell lines. Vectors described in the paper are available from Addgene.
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Yeung TK, Lau HW, Ma HT, and Poon RYC (2021) One-step multiplex toolkit for efficient generation of conditional gene silencing human cell lines. Mol. Biol. Cell 32: 1320-30.

Award
2021
Randy YC Poon has been awarded the Croucher Senior Research Fellowships 2021. This is the second time that Prof. Poon has been awarded the Senior Research Fellowship Award after receiving it in 2002.

Research Projects
2021
Randy YC Poon and Fangwei Wang (Zhejiang University) have been awarded a grant from the NSFC–RGC Joint Research Scheme to conduct collaborative studies on Aurora A kinase and Bora.
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Research Projects
2021
Randy YC Poon has been awarded a grant from the RGC GRF to study cyclin-dependent kinases.
Keeping it in the family – the implication of multiple cyclin-dependent kinases in human cells
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Paper
2020: Lok and co. discovered that weakening of the spindle-assembly checkpoint is a mechanism underlying mitotic slippage. As mitotic slippage is critical for both cancer development and effectiveness of a major class of cancer therapies, these new findings extend our fundamental understanding of how cancer cells develop in the first place and subsequently respond to therapies.
Lok TS, Wang Y, Xu WK, Xie S, Ma HT, and Poon RYC (2020) Mitotic slippage is determined by p31comet and the weakening of the spindle-assembly checkpoint. Oncogene 39: 2819-34.

Paper
2020: Joyce Mak demonstrated that inactivation of ATM acts synergistically with PARP1 inhibitors in promoting cell death in cancer cells. This study implies that ATM is an important anti-cancer target for therapies using PARP inhibitors.
Mak JPY, Ma HT, and Poon RYC (2020) Synergism between ATM and PARP1 inhibition involves DNA damage and abrogating the G2 DNA damage checkpoint. Molecular Cancer Therapeutics 19: 123-134.

Research Projects
2020: Research grants recently awarded to the group:
• RGC GRF (Randy YC Poon)
The origins and aftermaths of mitotic slippage
• RGC GRF (Ken Ma)
Investigating the novel roles of TRIP13 in MDM2/MDM4-p53 regulation
• Health and Medical Research Fund (Ken Ma)
Role of TRIP13 gene in hepatocelluar carcinoma development & disease progression
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Meeting
30 May 2019
2nd Workshop on Mitotic Fidelity, HKUST.
Organizer: R.Y.C. Poon
Speakers: Franco Au (HKUST), Gary Chan (HKU), William Chao (U Macau), Yick Hin Ling (HKU), Ken Ma (HKUST)

Resources
2019: a superior conditional KO system generated using CRISPR-Cas9 and rescue constructs under the control of Tet promoter and AID degron. Great for studying essential genes.
Vectors described in the paper can be obtained from Addgene.
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Ng LY, Ma HT, Liu JCY, Huang X, Lee N, and Poon RYC (2019) Conditional gene inactivation by combining tetracycline-mediated transcriptional repression and auxin-inducible degron-mediated degradation. Cell Cycle 18: 238-48.

Paper
2019: Zeng and co. addressed an important issue in anti-cancer drug responses. They found that mitotic slippage prevents mitotic cell death caused by spindle poisons but reduces subsequent long term survival. The specific temporal patterns of cell death may reconcile the contradictory results from many previous studies.
Zeng X, Xu WK, Lok TM, Ma HT, and Poon RYC (2019) Imbalance of the spindle-assembly checkpoint promotes spindle poison-mediated cytotoxicity with distinct kinetics. Cell Death and Disease 10: 314.

Research Project
2018
An industrial collaborative project with the CK Life Sciences International Inc on the development of cancer vaccines and immune checkpoint inhibitors is funded by the Innovation & Technology Council.
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Paper
2018: Ken Ma published a complementary paper to our 2016 study on TRIP13. This new study finally explains the paradox of why TRIP13 is required for the activation of the spindle-assembly checkpoint (in addition to its role in inactivating the checkpoint).
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Ma HT and Poon RYC (2018) TRIP13 functions in the establishment of the spindle-assembly checkpoint by replenishing O-MAD2. Cell Reports 22: 1439-50.
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Ma HT and Poon RYC (2016) TRIP13 regulates both the activation and inactivation of the spindle-assembly checkpoint. Cell Reports 14: 1086-99.

Research Projects
2018: Research grants recently awarded to the group:
• RGC GRF (Randy YC Poon)
Cyclin A: reassessing its mitotic functions with new arsenal
• RGC GRF (Ken Ma)
Understanding the role of TRIP13 and MAD2 conformation equilibrium in spindle assembly checkpoint
• RGC CRF (Randy YC Poon co-PI)
High-resolution live-cell imaging system for quantifying long-term 3D dynamics of large tissue models and organisms