Kyushu University Academic Staff Educational and Research Activities Database
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TSE KA FAI WILLIAM Last modified date:2024.06.03



Undergraduate School
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Homepage
https://kyushu-u.elsevierpure.com/en/persons/ka-fai-william-tse
 Reseacher Profiling Tool Kyushu University Pure
Phone
092-642-7046
Fax
092-642-2804
Academic Degree
Ph.D; Hong Kong Baptist University (Hong Kong S.A.R.)
Country of degree conferring institution (Overseas)
Yes Bachelor Doctor
Field of Specialization
Developmental Biology; Fish Osmoregulation; Experimental pathology
ORCID(Open Researcher and Contributor ID)
0000-0002-3738-0460
Total Priod of education and research career in the foreign country
08years00months
Outline Activities
Research:
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.

Education:
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
Research Interests
  • Rare disease model; Environmental toxicant screening; Developmental Toxicology; Integrated omics
    keyword : Zebrafish; Disease model; Rare diseases; Craniofacial Developmental Biology; Signaling pathways; Experimental pathology; Environmental Sciences; Pollutant; Developmental toxicology; PFAS; Fish osmoregulation; Osmotic stress; Gill; Gut; Medaka
    2006.09~2034.02.
  • disease pathogenesis
    keyword : zebrafish; disease model; disease mechanism
    2013.09.
  • developmental toxicology
    keyword : zebrafish; environmental pollutants
    2013.09.
  • osmoregulation
    keyword : fish; gill; cellular volume; ion transporters; cytoskeleton
    2006.09.
Academic Activities
Papers
1. Zulvikar Syambani Ulhaq, May-Su You, Yun-Jin Jiang, William Ka Fai Tse, p53 inhibitor or antioxidants reduce the severity of ethmoid plate deformities in zebrafish Type 3 Treacher Collins syndrome model, International Journal of Biological Macromolecules, DOI: 10.1016/j.ijbiomac.2024.131216, 266, 131216, 2024.05.
2. Zulvikar Syambani Ulhaq, Guido Barbieri Bittencourt, Gita Vita Soraya, Lola Ayu Istifiani, Syafrizal Aji Pamungkas, Yukiko Ogino, Dian Kesumapramudya Nurputra, William Ka Fai Tse, Association between glaucoma susceptibility with combined defects in mitochondrial oxidative phosphorylation and fatty acid beta oxidation, Molecular Aspects of Medicine, DOI: 10.1016/j.mam.2023.101238, 96, 101238, 2024.04, Glaucoma is one of the leading causes of visual impairment and blindness worldwide, and is characterized by the progressive damage of retinal ganglion cells (RGCs) and the atrophy of the optic nerve head (ONH). The exact cause of RGC loss and optic nerve damage in glaucoma is not fully understood. The high energy demands of these cells imply a higher sensitivity to mitochondrial defects. Moreover, it has been postulated that the optic nerve is vulnerable towards damage from oxidative stress and mitochondrial dysfunction. To investigate this further, we conducted a pooled analysis of mitochondrial variants related to energy production, specifically focusing on oxidative phosphorylation (OXPHOS) and fatty acid β-oxidation (FAO). Our findings revealed that patients carrying non-synonymous (NS) mitochondrial DNA (mtDNA) variants within the OXPHOS complexes had an almost two-fold increased risk of developing glaucoma. Regarding FAO, our results demonstrated that longer-chain acylcarnitines (AC) tended to decrease, while shorter-chain AC tended to increase in patients with glaucoma. Furthermore, we observed that the knocking down cpt1a (a key rate-limiting enzyme involved in FAO) in zebrafish induced a degenerative process in the optic nerve and RGC, which resembled the characteristics observed in glaucoma. In conclusion, our study provides evidence that genes encoding mitochondrial proteins involved in energy metabolisms, such as OXPHOS and FAO, are associated with glaucoma. These findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and may offer potential targets for therapeutic interventions in the future..
3. Zulvikar Syambani Ulhaq, Keigo Okamoto, Yukiko Ogino, William Ka Fai Tse, Dysregulation of Spliceosomes Complex Induces Retinitis Pigmentosa–Like Characteristics in sf3b4-Depleted Zebrafish, American Journal Of Pathology, DOI: 10.1016/j.ajpath.2023.05.008, 193, 9, 1223-1233, 2023.09, The SF3B4 gene encodes a highly conserved protein that plays a critical role in mRNA splicing. Mutations in this gene are known to cause Nager syndrome, a rare craniofacial disorder. Although SF3B4 expression is detected in the optic vesicle before it is detected in the limb and somite, the role of SF3B4 in the eye is not well understood. This study investigated the function of sf3b4 in the retina by performing transcriptome profiles, immunostaining, and behavioral analysis of sf3b4−/− mutant zebrafish. Results from this study suggest that dysregulation of the spliceosome complex affects not only craniofacial development but also retinogenesis. Zebrafish lacking functional sf3b4 displayed characteristics similar to retinitis pigmentosa (RP), marked by severe retinal pigment epithelium defects and rod degeneration. Pathway analysis revealed altered retinol metabolism and retinoic acid signaling in the sf3b4−/− mutants. Supplementation of retinoic acid rescued key cellular phenotypes observed in the sf3b4−/− mutants, offering potential therapeutic strategies for RP in the future. In conclusion, this study sheds light on the previously unknown role of SF3B4 in retinogenesis and provides insights into the underlying mechanisms of RP..
4. Zulvikar Syambani Ulhaq; William Ka Fai Tse, Perfluorohexanesulfonic acid (PFHxS) induces oxidative stress and causes developmental toxicities in zebrafish embryos, Journal of Hazardous Materials, DOI: 10.1016/j.jhazmat.2023.131722, 457, 131722, 2023.05, Perfluorohexanesulfonic acid (PFHxS) is a short-chain perfluoroalkyl substance widely used to replace the banned perfluorooctanesulfonic acid (PFOS) in different industrial and household products. It has currently been identified in the environment and human bodies; nonetheless, the possible toxicities are not well-known. Zebrafish have been used as a toxicant screening model due to their fast and transparent developmental processes. In this study, zebrafish embryos were exposed to PFHxS for five days, and various experiments were performed to monitor the developmental and cellular processes. Liquid chromatography-mass spectrometry (LC/MS) analysis confirmed that PFHxS was absorbed and accumulated in the zebrafish embryos. We reported that 2.5 µM or higher PFHxS exposure induced phenotypic abnormalities, marked by developmental delay in the mid-hind brain boundary and yolk sac edema. Additionally, larvae exposed to PFHxS displayed facial malformation due to the reduction of neural crest cell expression. RNA sequencing analysis further identified 4643 differentiated expressed transcripts in 5 µM PFHxS-exposed 5-days post fertilization (5-dpf) larvae. Bioinformatics analysis revealed that glucose metabolism, lipid metabolism, as well as oxidative stress were enriched in the PFHxS-exposed larvae. To validate these findings, a series of biological experiments were conducted. PFHxS exposure led to a nearly 4-fold increase in reactive oxygen species, possibly due to hyperglycemia and impaired glutathione balance. The Oil Red O’ staining and qPCR analysis strengthens the notions that lipid metabolism was disrupted, leading to lipid accumulation, lipid peroxidation, and malondialdehyde formation. All these alterations ultimately affected cell cycle events, resulting in S and G2/M cell cycle arrest. In conclusion, our study demonstrated that PFHxS could accumulate and induce various developmental toxicities in aquatic life, and such data might assist the government to accelerate the regulatory policy on PFHxS usage..
5. Lai, Keng Po; Zhu, Peng; Boncan, Delbert Almerick T.; Yang, Lu; Leung, Cherry Chi Tim; Ho, Jeff Cheuk Hin; Lin, Xiao; Chan, Ting Fung; Kong, Richard Yuen Chong; Tse, William Ka Fai, Integrated Omics Approaches Revealed the Osmotic Stress-Responsive Genes and Microbiota in Gill of Marine Medaka, MSYSTEMS, 10.1128/msystems.00047-22, 7, 2, 2022.04, Keng Po Lai, Peng Zhu, Delbert Almerick T. Boncan, Lu Yang, Cherry Chi Tim Leung, Jeff Cheuk Hin Ho, Xiao Lin, Ting Fung Chan, Richard Yuen Chong Kong, William Ka Fai Tse.
6. 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.
METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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..
7. 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..
8. 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
Educational Activities
I am involved in five courses in the IUP:

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



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