I am honored to apply to the HK Laureate Forum, a distinguished platform that unites visionary leaders dedicated to innovation and societal impact. As a scientist and leader in biotechnology, my work has focused on bridging the gap between fundamental research and real-world applications. My research on Metabolic Dysfunction‐associated Steatotic Liver Disease (MASLD) underscores the importance of viewing health as a dynamic interplay of metabolic dysfunction and aging, rather than isolated diseases. This holistic approach drives my commitment to advancing healthspan and developing transformative therapies.

My leadership extends beyond the laboratory. As a PhD candidate and former student government leader, I have forged interdisciplinary collaborations with biomedical engineers in Shenzhen, clinicians in Thailand, and researchers globally. These experiences have enriched my understanding of diverse healthcare systems and strengthened my ability to connect academia, industry, and policy.

The HK Laureate Forum offers an ideal environment to refine my leadership skills and expand my global network. I am eager to share my insights on translational research and systems‐level thinking while learning from fellow luminaries. I am eager to contribute to dynamic dialogues and initiatives at the Forum.

Lee Kong Chian School of Medicine, Nanyang Technological University Singapore

Lee Kong Chian School of Medicine, Nanyang Technological University Singapore

Recommendation-Letter-2-Prof-Sunny-Wong-Hei.pdf

Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver-related morbidity worldwide, yet the molecular links between gut barrier dysfunction and disease progression remain unclear. We identify intestinal Angiopoietin-like 4 (Angptl4) as a key regulator of gut–liver crosstalk that integrates dietary and microbial signals to drive gut permeability and hepatic oxidative stress—early hallmarks of MASH. Using intestinal-specific Angptl4 knockout mice and multi-cohort human studies, we demonstrate that Angptl4 expression is governed by four mechanisms: (1) host TLR expression patterns modulated by diet; (2) fatty acid-induced PPARα signaling; (3) shifts in Gram-negative to Gram-positive bacterial ratios that alter LPS levels; and (4) flagellin-triggered TLR5-EGR1 signaling upregulating Angptl4. These functional changes, rather than broad taxonomic shifts in the microbiota, mediate gut barrier breakdown and liver pathology. Notably, fecal Angptl4 serves as a robust non-invasive biomarker of gut permeability and MASLD severity, independent of traditional dysbiosis markers. While dietary reversion restores gut–liver homeostasis, inulin supplementation fails to reverse dysbiosis-driven permeability defects, underscoring the need for precision microbiome and metabolic interventions. Our findings establish Angptl4 as a novel therapeutic target at the interface of host metabolism and microbial signaling. This study offers novel insight into MASLD pathogenesis and emphasizes targeted, precision interventions for outcomes.