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Personal profile
Chinese Name
Biography
Dr. Wong holds a Bachelor of Science (BSc) from the University of Hong Kong. He pursued a PhD in Biochemistry at the Department of Biochemistry, University of Hong Kong.
Dr. Wong serves as a principal investigator at the School of Chinese Medicine, Hong Kong Baptist University, leading a team with expertise in biology, neuroscience, and microbiome research. In collaboration with clinicians and bioinformaticians, the pioneering work from his laboratory has led to multiple groundbreaking findings published in top-tier journals, including six papers in Nature Communications, one paper in Cell Host & Microbe, one article in Nature Metabolism, and one paper in Developmental Cell, in the capacity of first/corresponding author. In recognition of his research accomplishments, he was awarded the School Performance Award as Young Researcher in 2021, the President’s Award for Outstanding Performance as an Early Career Researcher in 2022, and the National Natural Science Foundation of China (NSFC) Excellent Young Scientist Fund (Hong Kong and Macau) in 2023. As the principal investigator, he has also secured approximately HK$20.1 million in research funding from competitive grant schemes in Hong Kong, Europe, and the Mainland to support his multidisciplinary translational research
Research Interests
My laboratory focuses on the systematic characterization of proteases to understand the regulation of cell biology, metabolic biology to control cellular disease phenotypes suggested by human genetics, molecular mechanisms to determine the roles of the microbiome in health and disease, and the molecular mechanisms uncovering patterns of human and microbial pathway regulation during disease and treatment. We develop a unique research program studying the interactions between the mammalian host and its microbiome, uncovering their effects on health and disease with particular interests in metabolic disorders and related gastrointestinal diseases. We utilize a variety of methodologies, including in vitro experiments, animal models, preclinical animal testing, advanced metabolic profiling, and genomic data analyses to uncover their functional crosstalk in human health and disease. Ultimately, we aim to translate our findings from the bench to bedside, supporting translational research in drug discovery and traditional Chinese Medicine.
Recently, my research team has uncovered how a series of proteolytic events predominantly mediated by MT1-MMP, a key cell-surface metalloproteinase involved in extracellular remodeling, contribute to the pathogenesis of metabolic disorders including obesity and diabetes. Despite all modern advances in medicine, an effective drug treatment for obesity has not been found yet. The discovery of GDF15, an appetite-regulatory hormone, two decades ago created hopes for the treatment of obesity. However, the development of GDF15 resistance has been a significant obstacle, mitigating a GDF15-centric treatment of obesity. My team has uncovered that the MT1-MMP-mediated cleavage of GFRAL, a key neuronal receptor of GDF15, controls the satiety center in the hindbrain, thereby regulating non-homeostatic appetite and body weight changes. This study, for the first time, reveals the molecular mechanism underlying the phenomenon of GDF15 resistance implicated in the pathogenesis of obesity (Nature Metabolism, 2022; research highlights in Nature Reviews Endocrinology, Nature Metabolism, and Science Signaling). By in silico drug screening, my team has recently discovered that artesunate, an FDA-approved anti-malaria drug derived from the herbal medicine qinghaosu (artemisinin), is a powerful anti-obesity agent that safely and effectively promotes weight loss in obesity by increasing GDF15 production and sensitivity (Nature Communications, 2024). Increased activation of MT1-MMP not only leads to higher risks of obesity but also causes age-associated insulin resistance by cleaving the insulin receptor in major metabolic tissues (Nature Communications, 2022a). To the best of my knowledge, this study shows increased insulin receptor cleavage as a causative factor for age-related insulin resistance and, more importantly, identifies the novel mechanism underlying this physiological observation with important clinical implications. Additionally, my team found that the activation of MT1-MMP is a determining factor for age-associated susceptibility to COVID-19 by regulating the proteolytic release of ACE2, a dominant entry receptor of SARS-CoV-2 (Nature Communications, 2022b). While evidence increasingly links the importance of soluble ACE2 with the infectivity of SARS-CoV-2, the underlying mechanism regulating the release of ACE2 from the cell surface has remained elusive. The identification of MT1-MMP as a major sheddase of ACE2 in my study therefore provides novel mechanistic insights into SARS-CoV-2 infection.
In addition to its pathological roles, I also demonstrated that the proteolytic events of MT1-MMP play an important role in various developmental processes through the regulation of multiple signaling pathways. MT1-MMP controls calvarial bone development by regulating FGF signaling (Developmental Cell, 2012; recommended by F1000Prime). Furthermore, MT1-MMP does not only function as a cell-surface protease for proteolysis but also translocates into the nucleus where it functions as a transcriptional factor controlling the inflammatory responses of immune cells (Nature Communications, 2016). My previous studies were among the first to highlight the importance of proteolysis as a mechanism of altering extracellular signaling, challenging the conventional wisdom that proteolysis is merely destructive. These studies have resulted in new concepts that challenged traditional views in various biological and pathological processes.
Another of my research interests focuses on the functional genomics of gastrointestinal bacteria in humans, with an emphasis on gut microbiota in gastrointestinal diseases and age-associated disorders. Recently, I identified gut dysbiosis as a leading cause of irritable bowel syndrome (IBS) and delineated a process through which bioactive metabolites derived from microbial catabolism of dietary amino acids trigger the development of diarrhea-predominant IBS (Cell Host & Microbe, 2023). Although the contribution of gut dysbiosis to IBS-D has been documented, this study is the first to identify a single bacterial species and its produced metabolites that directly trigger the development of IBS-D. I further demonstrated that the interplay between gut microbiota and host factors, including Nerve Growth Factor (NGF), regulates the transfer of intestinal stem cells from the quiescent niche to the proliferative niche in response to psychological stress, contributing to the development of IBS (Nature Communications, 2019). The concept of microbe-induced IBS-D proposed herein has important implications for the development of treatments for IBS and related disorders. In addition to gastrointestinal diseases, I also demonstrated that microbial shunting of amino acids into amines contributes to glucose intolerance and insulin resistance in both primates and non-primates (Nature Communications, 2023), which may pave the way for the identification of innovative microbiota-based diagnostics and/or therapeutics for the management of metabolic disease.
Selected publications (# correspondence)
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Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Education/Academic qualification
PhD, Department of Biochemistry, The University of Hong Kong
Award Date: 1 Oct 2013
Bachelor, Biochemistry & Biotechnology, School of Biological Sciences, Faculty of Science, The University of Hong Kong
Award Date: 1 Oct 2009
Keywords
- QP Physiology
- Cell Metabolism
- Cell signaling
- RB Pathology
- diabetes
- obesity
- QR180 Immunology
- Microbiome
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Collaborations and top research areas from the last five years
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To investigate the pathological role of microbiome-derived tryptamine and phenethylamine in the aspartame-induced insulin resistance
WONG, H. L. X. (PI)
1/01/25 → 31/12/27
Project: Research project
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Targeting osteoblastic 11β-HSD1 to combat high fat diet-induced bone loss, glucose handing impairment and obesity
LIU, J. (PI), WONG, H. L. X. (CoI), ZHANG, G. (CoI) & Wang, S. (CoI)
1/01/25 → 31/12/27
Project: Research project
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Dissecting the Therapeutic Role of 3A2 Antibody for the Treatment of Obesity and Type 2 Diabetes
WONG, H. L. X. (PI)
20/12/24 → 30/04/26
Project: Research project
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Equipment Matching Fund - High-performance Slide Scanner
LIU, J. (PI), LI, F. (CoI), YU, Y. (CoI), XU, J. (CoI), FU, X. (CoI), WONG, H. L. X. (CoI), KWAN, H. Y. (CoI) & CHONG, W. P. (CoI)
26/03/24 → 25/03/26
Project: Research project
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Dissecting the Therapeutic Role of 3A2 Antibody for the Treatment of Obesity and Type 2 Diabetes
WONG, H. L. X. (PI)
7/02/24 → 30/04/26
Project: Research project
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Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis
Guo, X., Asthana, P., Zhai, L., Cheng, K. W., Gurung, S., Huang, J., Wu, J., Zhang, Y., Mahato, A. K., Saarma, M., Ustav, M., Kwan, H. Y., Lyu, A., Chan, K. M., Xu, P., Bian, Z. X. & Wong, H. L. X., 3 Feb 2024, In: Nature Communications. 15, 1, 14 p., 1034.Research output: Contribution to journal › Journal article › peer-review
Open Access8 Citations (Scopus) -
Ruminococcus gnavus plays a pathogenic role in diarrhea-predominant irritable bowel syndrome by increasing serotonin biosynthesis
Zhai, L., Huang, C., Ning, Z., Zhang, Y., Zhuang, M., Yang, W., Wang, X., Wang, J., Zhang, L., Xiao, H., Zhao, L., Asthana, P., Lam, Y. Y., Chow, C. F. W., Huang, J. D., Yuan, S., Chan, K. M., Yuan, C. S., Lau, J. Y. N. & Wong, H. L. X. & 1 others, , 11 Jan 2023, In: Cell Host and Microbe. 31, 1, p. 33-44.e5 12 p.Research output: Contribution to journal › Journal article › peer-review
56 Citations (Scopus) -
Control of SARS-CoV-2 infection by MT1-MMP-mediated shedding of ACE2
Guo, X., Cao, J., Cai, J. P., Wu, J., Huang, J., Asthana, P., Wong, S. K. K., Ye, Z. W., Gurung, S., Zhang, Y., Wang, S., Wang, Z., Ge, X., Kwan, H. Y., Lyu, A., Chan, K. M., Wong, N., Huang, J., Zhou, Z. & Bian, Z. X. & 2 others, , 23 Dec 2022, In: Nature Communications. 13, 17 p., 7907.Research output: Contribution to journal › Journal article › peer-review
Open Access11 Citations (Scopus) -
Regulation of age-associated insulin resistance by MT1-MMP-mediated cleavage of insulin receptor
Guo, X., Asthana, P., Gurung, S., Zhang, S., Wong, S. K. K., Fallah, S., Chow, C. F. W., Che, S., Zhai, L., Wang, Z., Ge, X., Jiang, Z., Wu, J., Zhang, Y., Wu, X., Xu, K., Lin, C. Y., Kwan, H. Y., Lyu, A. & Zhou, Z. & 2 others, , 29 Jun 2022, In: Nature Communications. 13, 1, 10 p., 3749.Research output: Contribution to journal › Journal article › peer-review
Open Access24 Citations (Scopus) -
Body weight regulation via MT1-MMP-mediated cleavage of GFRAL
Chow, C. F. W., Guo, X., Asthana, P., Zhang, S., Wong, S. K. K., Fallah, S., Che, S., Gurung, S., Wang, Z., Lee, K. B., Ge, X., Yuan, S., Xu, H., Ip, J. P. K., Jiang, Z., Zhai, L., Wu, J., Zhang, Y., Mahato, A. K. & Saarma, M. & 7 others, , 17 Feb 2022, In: Nature Metabolism. 4, 2, p. 203–212 10 p.Research output: Contribution to journal › Journal article › peer-review
23 Citations (Scopus)
Prizes
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NSFC Excellent Young Scientists Fund (Hong Kong and Macao)
WONG, H. L. X. (Recipient), 2023
Prize: Award
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President's Award for Outstanding Performance as Early Career Researcher
WONG, H. L. X. (Recipient), 2022
Prize: Award
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Activities
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Gordon Research Conference: 2024 Plasminogen Activation and Extracellular Proteolysis
WONG, H. L. X. (Speaker)
18 Feb 2024 → 23 Feb 2024Activity: Conference/talk/lecture/symposium/speech/workshop, etc › Event organized by non-HKBU units
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Gordon Research Conference: Proteolytic Enzymes and Their Inhibitors
WONG, H. L. X. (Speaker)
9 Jun 2024 → 14 Jun 2024Activity: Conference/talk/lecture/symposium/speech/workshop, etc › Event organized by non-HKBU units
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BMJ Open Diabetes Research and Care (Journal)
WONG, H. L. X. (Reviewer)
12 Apr 2024Activity: Publication peer-review/editorial work › Editor/reviewer for publications (incl. CDCF T61 Journal Editor)
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Proteolysis at the membrane – from signaling to disease
WONG, H. L. X. (Speaker)
13 May 2024 → 16 May 2024Activity: Conference/talk/lecture/symposium/speech/workshop, etc › Event organized by non-HKBU units
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Obesity Reviews (Journal)
WONG, H. L. X. (Reviewer)
24 Mar 2024Activity: Publication peer-review/editorial work › Editor/reviewer for publications (incl. CDCF T61 Journal Editor)
Press/Media
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Press conference on potential of artemisinin derivative in treating human obesity
7/03/24
4 items of Media coverage, 2 Media contributions
Press/Media
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Press conference on cell entry mechanism of SARS-CoV-2 and therapeutic target for COVID-19
20/03/23
1 item of Media coverage
Press/Media
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Press conference on the new regulatory mechanism of satiety and therapeutic target for obesity research
30/05/22 → 31/05/22
5 items of Media coverage, 1 Media contribution
Press/Media