Kyushu University Academic Staff Educational and Research Activities Database
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KA FAI WILLIAM TSE Last modified date:2021.06.10

Undergraduate School
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 Reseacher Profiling Tool Kyushu University Pure
Academic Degree
Country of degree conferring institution (Overseas)
Yes Bachelor Doctor
Field of Specialization
Developmental Biology; Fish Osmoregulation
Total Priod of education and research career in the foreign country
Outline Activities
We have four major research themes:
1) Developmental functions of deubiquitylating enzyme: Deconjugation of ubiquitin and/or ubiquitin-like modified protein substrates is essential to modulate protein-protein interactions and, thus, signaling processes in cells. Although deubiquitylating (deubiquitinating) enzymes (DUBs) play a key role in this process, however, their function and regulation remain insufficiently understood. Our group performed the first genome-wide DUBs loss-of-function analysis in zebrafish, and we are now undergoing different experiments on selected DUBs to unfold their regulatory mechanisms and specific developmental functions. In 2013, we have identified that zebrafish transforming growth factor-β-stimulated clone 22 domain 3 (Tsc22d3) could function with two DUBs via the bone morphogenetic protein (bmp) pathway (Tse et al., 2013a). We are now working on the biochemical mechanism of the selected DUBs.

2) Disease model and mechanism: Zebrafish have been widely used in developmental biology, their well-established genome database and transparent embryos shaped them as an excellent developmental model. Recently, they are recruited as a new disease model. The zebrafish genome project identified that over 70% human disease causing genes can be found in the zebrafish genome. We own several organ-specific GFP-lines and mutants for different disease-based studies. Our group has a special interest on the mechanism of cleft lip and/or palate (CLP). CLP is one of the most common birth defects in the world, with an average frequency of 1/700. CLP besides affecting the appearance also causes significant morbidity in form and function. We selected several potential human CLP causing genes to study their functional roles in the facial development, which aim to understand the disease mechanism and thus identify small molecules to treat the disease before birth. Recently, we have identified the pathogenesis of the Type 3 Treacher Collins Syndrome by using a zebrafish model (Lau et al. 2016).

3) Osmoregulation: The capability of animal cells to maintain a constant cell volume is a prerequisite for cellular life. When eukaryotic cells are exposed to extracellular osmotic stress, they undergo rapid regulatory processes to maintain their cellular homeostatic status. The mechanism is particularly important in gill epithelia in fishes. Recently, our group applied the next-generation sequencing (NGS) and proteomics technologies to report the first eel gill specific transcriptome data and osmo-responsive proteins in eel gill (Tse et al. 2013b; Tse et al. 2014; Lai et al. 2015). Furthermore, our group use different fish models (eel, medaka, and zebrafish) to understand the molecular issues in the osmoregulation process (Chow et al. 2013; Lai et al. 2013; Tse et al. 2013c).

4) Developmental toxicity: Our group recently starts to apply developmental biology to environmental toxicology studies. Effects of toxicants on embryogenesis can be easily being tested in zebrafish embryos in a large scale. We have found that the exposure of environmental pollutant bisphenol A (BPA) and Triclosan could influence zebrafish embryos’ early development (Tse et al. 2013d) or lipid metabolism (Ho et al. 2016), respectively. Our group is now testing some other pollutants on their potential hazards on embryonic development.

I have teaching duties in the English-taught International undergraduate program, and am involved in the "Global Human Resource Development Project" (Hong Kong region).
Research Interests
  • disease pathogenesis
    keyword : zebrafish; disease model; disease mechanism
  • developmental toxicology
    keyword : zebrafish; environmental pollutants
  • osmoregulation
    keyword : fish; gill; cellular volume; ion transporters; cytoskeleton
Academic Activities
1. Li, Rong; Huang, Chen; Ho, Jeff Cheuk Hin; Leung, Cherry Chi Tim; Kong, Richard Yuen Chong; Li, Yu; Liang, Xiao; Lai, Keng Po; Tse, William Ka Fai, The use of glutathione to reduce oxidative stress status and its potential for modifying the extracellular matrix organization in cleft lip, FREE RADICAL BIOLOGY AND MEDICINE, 10.1016/j.freeradbiomed.2020.12.455, 164, 130-138, 2021.02, OBJECTIVE:
Cleft lip (CL) is a common congenital anomaly that can be syndromic or non-syndromic. It can be triggered by the mutation of gene or environmental factors. The incidence of CL is about 1 out of 700 live births. Facial development is a complex process, and there is no existing therapy to prevent the disease development. One of the characteristics in this facial malformation is the increased presence of reactive oxygen species (ROS). In this study, we hypothesize that the antioxidant glutathione (GSH) could help to attenuate the oxidative stress in this disease.
Bioinformatics network pharmacology was applied to determine pharmacological targets and molecular mechanisms of GSH treatment for CL. Moreover, RNA-sequencing of the POLR1C knockdown osteoblast CL model was applied to validate the in silico data of using GSH in CL.
Twenty-two core targets of GSH and CL were identified via various bioinformatics tools. The GO and KEGG analysis indicated that GSH could modulate two major families (matrix metalloproteinase and integrins), which are related to extracellular matrix modification and composition for facial development in CL. The findings from POLR1C knockdown model further supported the rescue response of GSH in CL.
The study uncovered the possible pharmacological mechanism of GSH for treating CL. The data helps research group to focus on the specific pathways for understanding the biological action of GSH for treating the CL in the future..
2. Lai, Keng Po; Lin, Xiao; Tam, Nathan; Ho, Jeff Cheuk Hin; Wong, Marty Kwok-Shing; Gu, Jie; Chan, Ting Fung; Tse, William Ka Fai, Osmotic stress induces gut microbiota community shift in fish, ENVIRONMENTAL MICROBIOLOGY, 10.1111/1462-2920.15150, 22, 9, 3784-3802, 2020.09, Alteration of the gut microbiota plays an important role in animal health and metabolic diseases. However, little is known with respect to the influence of environmental osmolality on the gut microbial community. The aim of the current study was to determine whether the reduction in salinity affects the gut microbiota and identify its potential role in salinity acclimation. Using Oryzias melastigma as a model organism to perform progressive hypotonic transfer experiments, we evaluated three conditions: seawater control (SW), SW to 50% sea water transfer (SFW) and SW to SFW to freshwater transfer (FW). Our results showed that the SFW and FW transfer groups contained higher operational taxonomic unit microbiota diversities. The dominant bacteria in all conditions constituted the phylum Proteobacteria, with the majority in the SW and SFW transfer gut comprising Vibrio at the genus level, whereas this population was replaced by Pseudomonas in the FW transfer gut. Furthermore, our data revealed that the FW transfer gut microbiota exhibited a reduced renin–angiotensin system, which is important in SW acclimation. In addition, induced detoxification and immune mechanisms were found in the FW transfer gut microbiota. The shift of the bacteria community in different osmolality environments indicated possible roles of bacteria in facilitating host acclimation..
3. Marco Chi Chung Lau, Ernest Man Lok Kwong, Keng Po Lai, Jing Woei Li, Jeff Cheuk Hin Ho, Ting Fung Chan, Chris Kong Chu Wong, Yun Jin Jiang, Ka Fai William Tse, Pathogenesis of POLR1C-dependent Type 3 Treacher Collins Syndrome revealed by a zebrafish model, Biochimica et Biophysica Acta - Molecular Basis of Disease, 10.1016/j.bbadis.2016.03.005, 1862, 6, 1147-1158, 2016.06, Treacher Collins Syndrome (TCS) is a rare congenital birth disorder (1 in 50,000 live births) characterized by severe craniofacial defects, including the downward slanting palpebral fissures, hypoplasia of the facial bones, and cleft palate (CP). Over 90% of patients with TCS have a mutation in the TCOF1 gene. However, some patients exhibit mutations in two new causative genes, POLR1C and POLR1D, which encode subunits of RNA polymerases I and III, that affect ribosome biogenesis. In this study, we examine the role of POLR1C in TCS using zebrafish as a model system. Our data confirmed that polr1c is highly expressed in the facial region, and dysfunction of this gene by knockdown or knock-out resulted in mis-expression of neural crest cells during early development that leads to TCS phenotype. Next generation sequencing and bioinformatics analysis of the polr1c mutants further demonstrated the up-regulated p53 pathway and predicted skeletal disorders. Lastly, we partially rescued the TCS facial phenotype in the background of p53 mutants, which supported the hypothesis that POLR1C-dependent type 3 TCS is associated with the p53 pathway..
Educational Activities
I am involved in five courses in the IUP:

Applied Cell Biology
Bioresource and Bioenvironment Experiments and Practice 1
Fundamental Cell Biology
Special Lecture on Advanced Topics of Agriculture 1

Professional and Outreach Activities
My group collaborates with different researchers around the world, such as China, Hong Kong, Germany, and Taiwan..