2023-11-30T16:11:31+08:002019-11-29|
Contact Information
Title
Associate Professor
Office
(Office) E12-3026 / (Lab) N22-4004a
Phone
(Office) +853 8822 4908 / (Lab) +853 8822 2936
Fax
+853 8822 2314
Email
williamchao@um.edu.mo
Consultation Hours

Mon, Thu 11:15 – 12:15

Teaching

HSCI1002 Introduction to Biological Sciences (BSc Course)

HSCI7002 Biomedical Sciences (MSc Course)

HSCI8005 Critical Scientific Reading, Writing and Analysis (PhD Course)

Research Team
Name Position Office Phone Email
Huadong LIPhD StudentN22-4003+853 8822 2934
Xijie GAOPhD Student
Education
PhD The Institute of Cancer Research, University of London, United Kingdom (2011)
MBiochem Molecular and Cellular Biochemistry, St Peter’s College, University of Oxford, United Kingdom (2007)
Position
09/2017 – Present Associate Professor, Faculty of Health Sciences, University of Macau
2012 – 2017 Cancer Research UK Additional Quota Fellow, London Research Institute / The Francis Crick Institute, London
2011 – 2012 Postdoctoral Fellow, The Institute of Cancer Research, London
Research Interests
Histone deacetylase complexes (HDACs) have emerged as transcriptional co-repressors, which serve to drive post-translational modifications on histone tails and nucleosome integrity. Aberrant expression and mutations of HDAC genes have been associated with a broad range of pathological conditions in particular cancer and aging. The involvement of HDACs in various diseases has prompted the development of histone deacetylase inhibitors (HDIs). Since several classes of HDACs are responsible for a broad range of biological processes, the ultimate goal is to develop specific HDIs that target a particular type of HDAC with no off-target effect. Due to the uneven physiological response to HDIs, only a few HDIs have been approved by drug safety regulatory bodies such as FDA. Thus, it is of paramount importance to consider the distinct HDAC structures during the development of specific HDIs.

 

My laboratory aims to unveil the atomic structures of apo and nucleosome-bound HDACs using cryo-EM. Structure of these HDACs will enable the scientific community to design HDIs that target a single HDAC complex with little off-target effect, potentially by disrupting the specific interactions between HDACs and nucleosomes.
Representative Publications
  1. Dong, S.*, Li, H.*, Wang, M.*, Rasheed, N.*, Zou, B., Gao, X., Guan, J., Li, W., Zhang, J., Wang, C., Zhou, N., Shi, X., Li, M., Zhou, M., Huang, J., Li, H., Zhang, Y., Wong, K. H., Zhang, X., Chao, W. C. H.#, He, J.#. Structural basis of nucleosome deacetylation and DNA linker tightening by Rpd3S histone deacetylase complex. Cell Res. (2023) 0:1–12. DOI: 10.1038/s41422-023-00869-1
  2. Tang, L.*, Dong, S., Rasheed, N.*, Wu, H. W.*, Zhou, N.*, Li, H., Wang, M., Zheng J.#, He J.#, Chao, W. C. H#. Vibrio parahaemolyticus prey targeting requires autoproteolysis-triggered dimerization of the type VI secretion system effector RhsP. Cell Rep. 41(10), 111732 (2022).
  3. Chen, O.J., Moustafa-Kamal, M., Barbara Rivera, J.N., Fahiminiya S., Wang Y., Gamache I., Pacifico C., Jiang L.,Carrot-Zhang J., Witkowski L., Berghuis A.M., Schönberger S., Schneider D., Hillmer M., Bens S., Siebert R., Stewart C.J.R., Zhang Z., Chao W.C.H., Greenwood C.M.T., Barford D., Tischkowitz M., Majewski J., Foulkes W.D., Teodoro J.G. (2022). Germline Missense Variants in CDC20 Result in Aberrant Mitotic Progression and Familial Cancer. Cancer Res. 82 (19): 3499–3515.
  4. Herst C.V., Burkholz S., Sidney J., Sette A., Harris P.E., Massey S., Brasel T., Cunha-Neto E., Rosa D.S., Chao W.C.H., Carback R., Hodge T., Wang L., Ciotlos S., Lloyd P., Rubsamen R. (2020). An effective CTL peptide vaccine for Ebola Zaire Based on Survivors’ CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design. Vaccine. 38 (28):4464-4475
  5. Chao, W.C.H.*,Wade, B.O.*, Bouchoux, C., Jones, A.W., Purkiss, A.G., Federico, S., O’Reilly, N., Snijders, A.P., Uhlmann, F., and Singleton, M.R. (2017). Structural basis of Eco1-mediated cohesin acetylation. Sci. Rep. 7:44313. doi:10.1038/srep44313
  6. Sansregret, L., Patterson, J.O., Dewhurst, S., López-García, C., Koch, A., McGranahan, N., Chao, W.C.H., Barry, D.J., Rowan, A., Instrell, R., Horswell, S., Way, M., Howell, M., Singleton, M.R., Medema, R.H., Nurse, P., Petronczki, M., Swanton, C. (2017). APC/C dysfunction limits excessive cancer chromosomal instability. Cancer Discov. 7(2); 1–16
  7. Chao, W.C.H., Murayama, Y., Muñoz, S., Jones, A.W., Wade, B.O., Purkiss, A.G., Hu, X.-W., Borg, A., Snijders, A.P., Uhlmann, F., Singleton, M.R. (2017). Structure of the cohesin loader Scc2. Nat. Commun 8, 13952.
  8. Chao, W.C.H., Murayama, Y., Muñoz, S., Costa, A., Uhlmann, F., and Singleton, M.R. (2015). Structural studies reveal the functional modularity of the Scc2-Scc4 cohesin loader. Cell Rep. 12, 719–725.
  9. Drosopoulos, K., Tang, C., Chao, W.C.H., and Linardopoulos, S. (2014). APC/C is an essential regulator of centrosome clustering. Nat. Commun. 5, 3686.
  10. He, J.*, Chao, W.C.H.*, Zhang, Z., Yang, J., Cronin, N., and Barford, D. (2013). Insights into degron recognition by APC/C coactivators from the structure of an Acm1-Cdh1 complex.  Mol. Cell 50, 649–660.
  11. Ferguson, J.L., Chao, W.C.H., Lee, E., and Friedman, K.L. (2013). The anaphase promoting complex contributes to the degradation of the S. cerevisiae telomerase recruitment subunit Est1p. PLoS ONE 8, e55055.
  12. Zhang, Z., Yang, J., Kong, E.H., Chao, W.C.H., Morris, E.P., da Fonseca, P.C.A., and Barford, D. (2013). Recombinant expression, reconstitution and structure of human anaphase-promoting complex (APC/C). Biochem. J. 449, 365–371.
  13. Chao, W.C.H.*, Kulkarni, K.*, Zhang, Z., Kong, E.H., and Barford, D. (2012). Structure of the mitotic checkpoint complex. Nature 484, 208–213.
  14. Brennan, D.F., Dar, A.C., Hertz, N.T., Chao, W.C.H., Burlingame, A.L., Shokat, K.M., and Barford, D. (2011). A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK. Nature 472, 366–369.

* co-first authorships
# co-corresponding authorships
Awards
2012 Cancer Research UK Additional Quota Fellowship, London Research Institute, London, United Kingdom
2012 Chairman’s Prize for Best PhD Student 2011, The Institute of Cancer Research, London, United Kingdom
Professional Activities
2021 – Present Secretary-General of the Talent Development Committee, Macau SAR Government
2020 – 2021 Committee Member of the Talent Development Committee, Macau SAR Government
2020 President of the Oxford and Cambridge Society of Macau (OCSM)
Grants
10/2021 – 10/2024 Molecular mechanism of Vibrio parahaemolyticus RhsP toxin release and RhsPI immunity protein as a protection against gastroenteritis (FDCT 0032/2021/A1)
01/2019 – 12/2021 Structural studies of the cohesin ring opening mechanism (MYRG2018-00221-FHS)
10/2018 – 10/2021 Structural studies of circadian clock and cell cycle coupling via the Timeless protein (FDCT 0009/2018/A1)