Staff Profile

Roles and Responsibilities

Qualifications

PhD

Memberships

The Genetics Society
British Society for Developmental Biology
British Society for Cell Biology

Undergraduate Teaching

BGM1005 Genetics Practical.

BMS2011 Extended Essay

BMS2002 Seminar

MBBS stage 1 Marking

CMB3000-Undergraduate Research Project Supervision 

Postgraduate Teaching

MMB8008 MRes Module Teaching, Module leader

"Cell Signalling in Health and Diseases" MRes Degree Programme Leader

MRes/MSc Research Project Supervision

Research Interests

Cell cycle control
Confocal and Fluorescence imaging
Drosophila genetics and developmental biology

Other Expertise

Drosophila Genetics, molecular biology and biochemistry

Current Work

Faulty cell division leads to aneuploidy and genetic instabilities that contribute to the progression of cancers and many other diseases including birth defects and Alzheimer's. To prevent this from happening, cells have evolved a mitotic surveillance mechanism, the spindle assembly checkpoint (SAC), to ensure a mother cell segregates its duplicated genomes equally into its two daughter cells with high fidelity during mitosis. Many important proteins involved in this process have been identified, but exactly how they relay signals to coordinate the faithful mitotic progression still remain to be answered. This lab uses biochemical, genetic, transgenic and microscopic methods to tackle these problems in Drosophila melanogaster (the fruit fly). Drosophila is an extremely tractable experimental system, a much simpler and better-understood organism compared to the human but shares fundamental processes in common. The SAC mechanism involves the proteins Mad2, BubR1 and Cdc20. Mad2 and BubR1 are inhibitors of the APC/C, an E3 ubiquitin ligase, while Cdc20 is an activator. Once activated, SAC can inactivate the APC/C to prevent destruction of two major mitotic regulators, Cyclin B and Securin, thus delaying the sister chromatid segregation. We have shown that the destruction of the Cyclin B is spatial-temporal regulated and that two APC/C core subunits, Cdc27 and Cdc16 are not always colocalised within cells. Cdc27 associates with mitotic chromosomes, but Cdc16 does not. This raises an intriguing possibility, that the activity of the mitotic APC/C is also spatial- temporally regulated. We also show that the SAC component BubR1, but not Mad2, is required for Cdc20 kinetochore recruitment. This provides an important new insight into the SAC mechanism. The functional interactions between the SAC mechanism and the apoptosis pathway are also under investigation.

Research Roles

Principal investigator.

Funding

Wellcome Trust Project Grant:RES/0120/7244
Wellcome Trust Project Grant:RES/0120/7360
BBSRC equivalent, Faculty funded PhD studentship.
BBSRC DTA PhD studentship.

• Li J, Dang M, MartinezLopez N, Jowsey PA, Huang D, Lightowlers RN, Gao F, Huang JY. M2I‑1 disrupts the in vivo interaction between CDC20 and MAD2 and increases the sensitivities of cancer cell lines to anti‑mitotic drugs via MCL‑1s. Cell Division 2019, 14(5).
• Li J, Dang N, Wood DJ, Huang J-Y. The kinetochore-dependent and -independent formation of the CDC20-MAD2 complex and its functions in HeLa cells. Scientific Reports 2017, 7, 41072.
• Herriott A, Sweeney M, Whitaker M, Taggart M, Huang JY. Kinetochore localized Mad2 and Cdc20 is itself insufficient for triggering the mitotic checkpoint when Mps1 is low in Drosophila melanogaster neuroblasts. Cell Cycle 2012, 11(24), 4650-4660.
• Sinclair M, Huang JY. Studying Mitotic Checkpoint by Illustrating Dynamic Kinetochore Protein Behavior and Chromosome Motion in Living Drosophila Syncytial Embryos. Journal of Visualized Experiments 2012, (64), e3763.
• Li D, Morley G, Whitaker M, Huang JY. Recruitment of Cdc20 to the kinetochore requires BubR1, but not Mad2 in Drosophila melanogaster. Molecular and Cellular Biology 2010, 30(13), 3384-3395.
• Zhao XA, Hume SL, Johnson C, Thompson P, Huang JY, Gray J, Lamb HK, Hawkins AR. The transcription repressor NmrA is subject to proteolysis by three Aspergillus nidulans proteases. Protein Science 2010, 19(7), 1405-1419.
• Kisielewska J, Philipova R, Huang JY, Whitaker M. MAP kinase dependent cyclinE/cdk2 activity promotes DNA replication in early sea urchin embryos. Developmental Biology 2009, 334(2), 383-394.
• Herriott A, Whitaker M, Huang JY. Investigation into spindle assembly checkpoint function in Drosophila melanogaster. In: Meeting on The Cell Cycle. 2010, Cold Spring Harbor, New York: National Cancer Institute.
• Huang J-Y, Morley G, Li D, Whitaker M. Cdk1 phosphorylation sites on Cdc27 are required for correct chromosomal localisation and APC/C function in syncytial Drosophila embryos. Journal of Cell Science 2007, 120(12), 1990-1997.
• Li D, Karess R, Whitaker M, Huang J-Y. BubR1, but not Mad2, is required for recruiting and localizing of Fzy to the kinetochores in D. melanogaster. In: 48th Annual Drosophila Research Conference. 2007, Philadelphia, Pennsylvania: The Genetics Society of America.
• Buffin E, Lefebvre C, Huang J, Gagou ME, Karess RE. Recruitment of Mad2 to the kinetochore requires the Rod/Zw10 complex. Current Biology 2005, 15(9), 856-861.
• Philipova R, Kisielewska J, Lu P, Larman M, Huang J-Y, Whitaker M. ERK1 activation is required for S-phase onset and cell cycle progression after fertilization in sea urchin embryos. Development 2005, 132(3), 579-589.
• Raff JW, Jeffers K, Huang JY. The roles of Fzy/Cdc20 and Fzr/Cdh1 in regulating the destruction of cyclin B in space and time. The Journal of Cell Biology 2002, 157(7), 1139-1149.
• Huang JY, Raff JW. The dynamic localisation of the Drosophila APC/C: evidence for the existence of multiple complexes that perform distinct functions and are differentially localised. Journal of Cell Science 2002, 115(14), 2847-2856.
• Huang JY, Jordan Raff JW. The dynamic localization of the Drosophila APC/C: evidence for the existence of multiple complexes that perform distinct functions and are differentially localized. In: BSCB/BSDB and Genetics Society Joint Spring Meeting. 2002, Heslington, York, UK.
• Chroust K, Jowett T, Farid-Wajidi MF, Huang J-Y, Ryskova M, Wolf R, Holoubek I. Activation or detoxification of mutagenic and carcinogenic compounds in transgenic Drosophila expressing human glutathione S-transferase. Mutation Research - Genetic Toxicology and Environmental Mutagenesis 2001, 498(1-2), 169-179.
• Huang JY, Raff JW. The disappearance of cyclin B at the end of mitosis is regulated spatially in Drosophila cells. The EMBO Journal 1999, 18(8), 2184-95.
• Jowett T, Huang J-Y, Murray S. Drug Resistance in Insects. In "Molecular Genetics of Drug Resistance" (1997) pp. 175-220. Ed. C.R. Wolf and J. D. Hayes. Modern Genetics Series Ed. J Evans. Publ. Harwood Academic Publishers GMBH ISBN 90-5702-168-4<br>(Review) 1997.
• Huang J-Y, Herriott A, Morley G, Deak P, Pal M. A deficiency of the Cdk1 phosphorylation of fizzy increases the binding affinity to cyclin B and reduces the affinities to BubR1 and Mad2 in Drosophila melanogaster. In: 23rd European Drosophila Research Conference. 2013, Barcelona, Spain: EDRC.