2021-09-08T10:37:30+08:002019-12-03|
Contact Information
Research Team
Name Position Office Phone Email
Fang WANGPhD StudentN22-3003+853 8822 4232
Liguo DONGPhD StudentN22-3003+853 8822 4232
Zhengqiang MIAOPhD StudentN22-3003+853 8822 4232
Zhiqiang DONGPhD StudentN22-3004+853 8822 4131
Qing LANPhD StudentN22-3004+853 8822 4131
Yimin ZHENGPhD StudentN22-3004+853 8822 4131
Weng In CHONGPhD StudentN22-3004+853 8822 4131
Yile FUPhD StudentN22-3004+853 8822 4131
Education
PhD Department of Genetics, The University of Melbourne, Australia (2007)
BSc (1st Class Hons) Department of Genetics, The University of Melbourne, Australia (2002)
BSc Faculty of Science, The University of Melbourne, Australia (2001)
Diploma Biotechnology, Ngee Ann Polytechnic, Singapore (1999)
Positions
2020-present Associate Professor, Faculty of Health Sciences, University of Macau
2013-2020 Assistant Professor, Faculty of Health Sciences, University of Macau
2008-2013 Postdoctoral Research Fellow, Department of Biochemistry and Molecular Pharmacology, Harvard Medical School, USA
2007-2008 Postdoctoral Research Fellow, Department of Genetics, The University of Melbourne, Australia
Research Interests
My research focuses on two broad aims:

  • To understand how pathogenic fungi cause diseases in humans.
  • To understand how transcription is regulated.

Why study Fungal Pathogenesis?

Fungal pathogens are ubiquitous in the environment, but they usually do not post serious threats to people with a healthy immune system. However, fungal pathogens can cause life-threatening diseases in individuals with a compromised immune system. In recent years, the number of immuno-compromised individuals is escalating as chemotherapy, bone marrow-transplant and organ-transplant therapies are becoming common medical procedures. Prevention and treatment of fungal infections has become a major clinical challenge. The situation is exacerbated by the lack of effective anti-fungal therapies with fatality rates of certain fungal infections being as high as 100%. Therefore, understanding fungal pathogenesis has immense medical implications and will provide valuable information towards development of new effective and life-saving anti-fungal treatments.

Why study Transcription Regulation?

Transcription is an essential molecular process whereby stored biological information is retrieved from the genome of living organisms. Proper and precise control of transcription is of fundamental importance to biology. Defects in this process are linked to many human diseases including cancers. The molecular mechanisms of transcriptional regulation in eukaryotic organisms are remarkably conserved from humans to fungi. In fact, much of our current knowledge of transcription regulation has come from fungal studies. Through studying transcription regulation in fungi, my research aims to provide important new information that is directly relevant to transcription regulatory mechanisms in humans.

Representative Publications
Journal Publication

  1. Wang, F., Sethiya, P., Hu, X., Guo, S., Chen, Y., Li, A., Tan, K. and Wong, K.H. “Transcription in fungal conidia before dormancy produces phenotypically variable conidia that maximize survival in different environments.” Nature Microbiology 2021; 6,1066–1081.
    https://rdcu.be/cnlx8
    。Featured on the cover page of August 2021 issue.
    https://www.nature.com/nmicrobiol/volumes/6/issues/8
    。Featured in: Blatzer, M., Latgé, JP. Fungal spores are future-proofed. Nature Microbiology 2021;6,979–980.
    https://doi.org/10.1038/s41564-021-00946-4
  2. dos Reis T.F., Horta M.A.C., Colabardini A.C., Fernandes C.M., Silva L.P., Bastos R.W., Fonseca M.V.D.L., Wang F., Martins C., Rodrigues M.L., Silva Pereira C., Del Poeta M., Wong, K.H. and Goldman, G.H. “Screening of Chemical Libraries for New Antifungal Drugs against Aspergillus fumigatus Reveals Sphingolipids Are Involved in the Mechanism of Action of Miltefosine.” mBIO 2021;12(4): e01458-21.
    https://doi.org/10.1128/mBio.01458-21
  3. Castro, P., Valero, C., Chiaratto, J., Colabardini, A.C., Pardeshi, L., Silva, L., Almeida, F., Rocha, M.C., Malavazi, I., Silva, R., Du, W., Dyer, P., Brock, M., Loures, F., Wong, K.H. and Goldman G. “Novel biological functions for the Aspergillus fumigatus NsdC transcription factor homologue involved in sexual development” mBIO 2021;12:e03102-20.
    https://doi.org/10.1128/mBio.03102-20
  4. Assis, L.J., Silva, L.P., Bayram, O., Dowling, P., Kniemeyer, O., Krüger, T., Brakhage, A.A., Chen, Y., Dong, L., Tan, K., Wong, K.H., Ries, L.N.A. and Goldman, G. “Carbon catabolite repression in filamentous fungi is regulated by phosphorylation of the transcription factor CreA” mBIO 2021;12:e03146-20.
    https://doi.org/10.1128/mBio.03146-20
  5. Liu, J., Adhav, R., Miao, K., Su, S.M., Mo, L., Chan, U.I., Zhang, X., Xu, J., Li, J., Shu, X., Zeng, J., Zhang, X., Lyu, X., Pardeshi, L., Tan, K., Sun, H., Wong, K.H., Deng, C.X. and Xu, X. “Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5as a tumor metastasis suppressor.” Nature Communications 2020; 11(1):4875.
    https://doi: 10.1038/s41467-020-18637-9
  6. Ries, L., Pardeshi, L., Dong, Z., Tan, K., Steenwyk, J., Cristina Colabardini, A., Filho, J., Preite, N., Almeida, F., Jose de Assis, L., Santos, R., Bowyer, P., Bromley, M., Owens, R., Doyle, S., Demasi, M., Hernández, D., Netto, L., Pupo, M., Rokas, A., Loures, F., Wong, K.H. * and Goldman, G.* “The Aspergillus fumigatus transcription factor RglT is essential for virulence, gliotoxin biosynthesis and self-protection.” PLoS Pathogen 2020; 16(7): e1008645. (* Co-corresponding author)
    https://doi.org/10.1371/journal.ppat.1008645
  7. Zhou, P., Chan, B., Wan, Y.K., Yuen, C., Choi, G., Li, X., Cheung, L., Tan, K., Wong, K.H., Chan, H.Y.E. and Wong, A.S.L “A Three-way combinatorial CRISPR screen for analyzing interactions among druggable targets.” Cell Reports 2020; 32, 108020.
    https://doi.org/10.1016/j.celrep.2020.108020
  8. Kai, M., Lei, H., Valecha, M.V., Zhang, A., Xu, J., Wang, L., Lyu, X., Chen, S., Miao, Z., Zhang, X., Su, S., Shao, F., Rajendran, B.K., Bao, J., Zeng, J., Sun, H., Chen, P., Tan, K., Chen, Q., Wong, K.H., Xu, X. and Deng, C.X. “NOTCH1 Activation Compensates BRCA1 Deficiency and Promotes Triple-Negative Breast Cancer Formation.” Nature Communications 2020; 11, 3256.
    https://doi.org/10.1038/s41467-020-16936-9
  9. Valero, C., Colabardini, A.C., Chiaratto, J., Pardeshi, L., Castro, P., Filho, J.F., Silva, L., Rocha, M., Malavazi, I., Costa, J., Fill, T., Barros, M., Wong, S., Aimanianda, V., Wong, K.H. and Goldman G. “Aspergillus fumigatus transcription factors involved in the caspofungin paradoxical effect.” mBio 2020; 11:e00816-20.
    https://doi.org/10.1128/mBio .00816-20
  10. Sethiya, P., Rai, M.N., Rai, R., Parsania, C., Tan, K. and Wong, K.H. “Transcriptomic analysis reveals global and temporal transcription changes during Candida glabrata adaptation to an oxidative environment.” Fungal Biology 2020;124(5):427-439.
    https://doi.org/10.1016/j.funbio.2019.12.005
  11. Yan, J., Bhadra, P., Li, A., Sethiya, P., Qin, L., Tai, H.K., Wong, K.H. and Siu, S.W.I. “Deep-AmPEP30: Improve short antimicrobial peptides prediction with deep learning.” Molecular Therapy – Nucleic Acids
    https://doi.org/10.1016/j.omtn.2020.05.006
  12. Choi, G.C.G., Zhou, P., Yuen, C.T.L., Chan, B.K.C., Xu, F., Bao, S., Chu, H.Y., Thean, D., Tan, K., Wong, K.H., Zheng, Z. and Wong, A.S.L. “Combinatorial mutagenesis en masse optimizes the genome editing activities of SpCas9” Nature Methods 2019; 16:722-730.
    https://www.nature.com/articles/s41592-019-0473-0
  13. Petrenko, N., Jin, Y., Dong, L., Wong, K.H. *# and Struhl, K#. “Requirements for RNA polymerase II preinitiation complex formation in vivo.” eLife 2019; 8:e43654. (# Corresponding author)
    https://doi.org/10.7554/eLife.43654
  14. Kim, S.H., Iyer, K.R., Pardeshi, L., Munoz, J.F., Robbins, N., Cuomo, C.A., Wong, K.H. and Cowen, L.E. “Genetic analysis of Candida auris implicates Hsp90 in morphogenesis and Azole tolerance and Cdr1 in Azole resistance.” mBio 2019; 10(1). pII:e02529-18.
    https://mbio.asm.org/content/10/1/e02529-18
  15. Tan, K. and Wong, K.H. “RNA polymerase II ChIP-seq—a powerful and highly affordable method for studying fungal genomics and physiology.” Biophysical Reviews
    https://rdcu.be/bf1ib
  16. Veri, A.O., Miao, Z., Shapiro, R.S., Tebbji, F., O’Meara, T.R., Kim, S.H., Colazo, J., Tan, K., Vyas, V.K., Whiteway, M., Robbins, N., Wong, K.H., and Cowen L.E. “Tuning Hsf1 levels drives distinct fungal morphogenetic programs with depletion impairing Hsp90 function and overexpression expanding the target space.” PLoS Genetics 2018; 14(3): e1007270.
    https://doi.org/10.1371/journal.pgen.1007270
  17. Xie, J.L., Qin, L., Miao, Z., Grys, B.T., Diaz, J.D.L.C., Ting, K., Krieger, J.R., Tong, J., Tan, K., Leach, M.D., Ketela, T., Moran, M.F., Krysan, D.J., Boone, C., Andrews, 
 B.J., Selmecki, A., Wong, K.H., Robbins, N. and Cowen, L.E. “The Candida albicans Transcription Factor Cas5 Couples Stress Responses, Drug Resistance, and Cell Cycle Regulation.” Nature Communications 2017; 8(1):499.
    https://www.nature.com/articles/s41467-017-00547-y
  18. Petrenko, N.*, Jin, Y.*, Wong, K.H.* and Struhl, K. “Evidence that Mediator is essential for Pol II transcription, but is not a required component of the preinitiation complex in vivo.” eLife 2017; 6:e28447. (* Equal contribution)
    https://doi.org/10.7554/eLife.28447.001
  19. Szot, P.S., Yang, A., Wang, X., Parsania, C., Rohm, U., Wong, K.H. and Ho, J.W.K. “PBrowse: a web-based platform for real-time collaborative exploration of genomic data.” Nucleic Acids Research. 2017; 45 (9): e67.
    https://doi.org/10.1093/nar/gkw1358
  20. Petrenko, N.*, Jin, Y.*, Wong, K.H.*# and Struhl, K#. “Mediator undergoes a compositional change during transcriptional activation.” Molecular Cell. 2016; 64(3):443-454. (* Equal contribution; # Corresponding author)
    https://doi.org/10.1016/j.molcel.2016.09.015
    Featured in: Malik, S., and Roeder, G.R. “Mediator: A Drawbridge across the Enhancer-Promoter Divide.” Molecular Cell. 2016; 64(3):433-434.
    https://doi.org/10.1016/j.molcel.2016.10.024
  21. Leach, M.D., Farrer, R.A., Tan, K., Miao, Z., Walker, L.A., Cuomo, C.A., Wheeler, R.T., Brown, A.J.P., Wong, K.H. and Cowen, L.E. “Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodeling and chromatin architecture in Candida albicans.” Nature Communications. 2016 7:11704.
    https://www.nature.com/articles/ncomms11704
  22. Wong, K.H.*, Jin, Y.*, and Struhl, K. “TFIIH phosphorylation of the Pol II CTD stimulates Mediator dissociation from the preinitiation complex and promoter escape.” Molecular Cell. 2014; 54(4): 601-612. (* Equal contribution)
    https://doi.org/10.1016/j.molcel.2014.03.024
  23. Wong, K.H.*, Jin, Y., and Moqtederi, Z. “Multiplex Illumina sequencing using DNA-barcoding.” Current Protocol in Molecular Biology. 2013; Chapter 7:Unit 7.11. (Invited protocol) (* Corresponding author)
    https://doi.org/10.1002/0471142727.mb0711s101
  24. Wong, K.H., and Struhl, K. “The Cyc8−Tup1 complex inhibits transcription primarily by masking the activation domain of the recruiting protein.” Genes and Development. 2011 Dec 1; 25: 2525-2539.
    http://www.genesdev.org/cgi/doi/10.1101/gad.179275.111
    Featured in: Parnell, E.J., and Stillman, D.J. “Shields up: the Tup1−Cyc8 repressor complex blocks coactivator recruitment.” Genes and Development. 2011 Dec 1, 25: 2429-2435.
    http://www.genesdev.org/cgi/doi/10.1101/gad.181768.111
  25. Tirosh, I.*, Wong, K.H.*, Barkai, N., and Struhl, K. “Extensive divergence of yeast stress responses through transitions between induced and constitutive activation.” Proceedings of the National Academy of Sciences of USA. 2011 Oct 4; 108(40):16693-8. (* Equal contribution)
    https://doi.org/10.1073/pnas.1113718108
  26. Suk, K., Choi, J., Suzuki, Y., Ozturk, SB., Mellor, JC., Wong, K.H., MacKay, JL., Gregory, R.I., and Roth, F.P. “Reconstitution of human RNA interference in budding yeast.” Nucleic Acids Research. 2011 Apr; 39(7):e43.
    https://doi.org/10.1093/nar/gkq1321
  1. Wong, K.H., Hynes, M.J., Todd, R.B., and Davis, M.A. “Deletion and overexpression of the Aspergillus nidulans GATA factor AreB reveals unexpected pleiotropy.” Microbiology. 2009 Dec; 155(Pt 12):3868-80.https://dx.doi.org/10.1099/mic.0.031252-0
  1. Wong, K.H., Hynes, M.J., and Davis, M.A. “Recent advances in nitrogen regulation: a comparison between yeast and filamentous fungi.” Mini-review. Eukaryotic Cell. 2008 7(6):917-925.
    https://ec.asm.org/content/7/6/917
  2. Wong, K.H., Todd, R.B., Oakley, B.R., Oakley, C.E, Hynes, M.J., and Davis, M.A. “Sumoylation in Aspergillus nidulans: sumO inactivation, overexpression and live-cell imaging.” Fungal Genetics and Biology. 2008 45:728-737.
    https://doi.org/10.1016/j.fgb.2007.12.009
  3. Wong, K.H., Hynes, M.J., Todd, R.B., and Davis, M.A. “Transcriptional control of nmrA by the bZIP transcription factor MeaB reveals a new level of nitrogen regulation in Aspergillus nidulans.” Molecular Microbiology. 2007 66(2):534-551.
    https://doi.org/10.1111/j.1365-2958.2007.05940.x

Book Chapter

  • Davis, M.A. and Wong, K.H. “Chapter 23: Nitrogen Metabolism in Filamentous Fungi.” In: Cellular and Molecular Biology of Filamentous Fungi edited by Borkovich, Katherine A. and Ebbole, Daniel J. © 2010 American Society for Microbiology (ASM). (Invited book chapter)
Full publications list
Awards
2013 Marine Biological Laboratory Scholarship, Marine Biological Laboratory, USA
2009-2010 Croucher Postdoctoral Fellowship,The Croucher Foundation, Hong Kong
2003-2006 International Postgraduate Research Scholarship (IPRS), The Australian Government
2003-2006 Melbourne International Research Scholarships (MIRS), The University of Melbourne, Australia
2001-2003 Howitt Natural History Scholarship, The University of Melbourne, Australia
2003 The Department of Genetics Postgraduate Scholarship, The University of Melbourne, Australia
2002 The Department of Genetics Honours Scholarship, The University of Melbourne, Australia
2002 Dean’s Honour List – B.Sc.(Hons), Faculty of Science, The University of Melbourne, Australia
Professional Activities
  • Member of the Genetics Society of America