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Revised DEC 2025
Main Research Theme
Main Research Theme
Unlocking Next-Generation Therapeutics for Cancer, Metabolism, and Aging via AI and Single-cell/Spatial Multi-omics
Unlocking Next-Generation Therapeutics for Cancer, Metabolism, and Aging via AI and Single-cell/Spatial Multi-omics
Our laboratory is dedicated to decoding the multiscale regulatory architectures governing the interplay between the tumor microenvironment, metabolic plasticity, and epigenetic aging. By leveraging high-resolution single-cell/spatial multiomics and explainable deep learning models, we engineer next-generation precision medicine strategies designed to therapeutically modulate targets previously deemed undruggable.
Our laboratory is dedicated to decoding the multiscale regulatory architectures governing the interplay between the tumor microenvironment, metabolic plasticity, and epigenetic aging. By leveraging high-resolution single-cell/spatial multiomics and explainable deep learning models, we engineer next-generation precision medicine strategies designed to therapeutically modulate targets previously deemed undruggable.
Current Research Topics
Current Research Topics
Decoding the cancer microenvironment for next-generation therapy
Using single-cell, spatial, and deep multi-omics, we decode actionable tumor–immune–stroma circuits that govern therapy response, then engineer interventions—neoantigen vaccines, CAR-macrophage reprogramming, phosphorylation-network vulnerabilities, and therapy-induced senescence-driven resistance targeting—to convert “cold” tumors into immunologically tractable states.
Decoding the cancer microenvironment for next-generation therapy
Using single-cell, spatial, and deep multi-omics, we decode actionable tumor–immune–stroma circuits that govern therapy response, then engineer interventions—neoantigen vaccines, CAR-macrophage reprogramming, phosphorylation-network vulnerabilities, and therapy-induced senescence-driven resistance targeting—to convert “cold” tumors into immunologically tractable states.
Selected papers from our lab on this topic:
Nature Communications. 11, 951 (2020) - We built a deep-learning framework that prioritizes clinically relevant neoantigens and functional immune-evasion mutations, providing a computational launchpad for microenvironment-aware vaccine and immunotherapy stratification.
Clinical and Translational Medicine. 12, e714 (2022) - Demonstrated that tumour-essential genes shape neoantigen-directed immunoediting and immune escape, motivating microenvironment-aware therapeutic targeting.
Selected papers from our lab on this topic:
Nature Communications. 11, 951 (2020) - We built a deep-learning framework that prioritizes clinically relevant neoantigens and functional immune-evasion mutations, providing a computational launchpad for microenvironment-aware vaccine and immunotherapy stratification.
Clinical and Translational Medicine. 12, e714 (2022) - Demonstrated that tumour-essential genes shape neoantigen-directed immunoediting and immune escape, motivating microenvironment-aware therapeutic targeting.
Signal Transduction and Targeted Therapy. 9, 274 (2024)
Metabolic precision at the intersection of cancer and obesity
We study cancer metabolism and obesity biology in parallel, with a shared emphasis on how nutrient transport and metabolic stress programs rewire cell states and reshape tissue ecosystems. In cancer, we pursue metabolism-linked vulnerabilities that enforce immune exclusion or therapy resistance; in obesity, we dissect systemic metabolic remodeling that alters tissue inflammation and immune competence—then connect the two through convergent mechanisms that may determine cancer risk and treatment outcome.
Metabolic precision at the intersection of cancer and obesity
We study cancer metabolism and obesity biology in parallel, with a shared emphasis on how nutrient transport and metabolic stress programs rewire cell states and reshape tissue ecosystems. In cancer, we pursue metabolism-linked vulnerabilities that enforce immune exclusion or therapy resistance; in obesity, we dissect systemic metabolic remodeling that alters tissue inflammation and immune competence—then connect the two through convergent mechanisms that may determine cancer risk and treatment outcome.
Selected papers from our lab on this topic:
Selected papers from our lab on this topic:
Nature Communications 15, 10164 (2024) - We defined NSCLC subtypes with distinct metabolic signaling and immune niches through deep proteogenomics, illustrating how multi-omics can reveal actionable “metabolic–immune states” for precision therapy.
Nature Reviews Cancer. 20, 516-531 (2020)
Noncanonical DNA dynamics in immune cell development and aging
We uncover how noncanonical DNA/RNA structures—including G-quadruplexes and R-loops—and their regulators (e.g., helicases such as DHX9) reshape chromatin and transcriptional programs during immune cell development and drive aging trajectories; our earlier environmental epigenetics work provides a life-course foundation for exposure-linked epigenetic “scars,” now informing a transition toward mechanistic, structure-centric models of immune maturation and aging.
Noncanonical DNA dynamics in immune cell development and aging
We uncover how noncanonical DNA/RNA structures—including G-quadruplexes and R-loops—and their regulators (e.g., helicases such as DHX9) reshape chromatin and transcriptional programs during immune cell development and drive aging trajectories; our earlier environmental epigenetics work provides a life-course foundation for exposure-linked epigenetic “scars,” now informing a transition toward mechanistic, structure-centric models of immune maturation and aging.
Selected papers from our lab on this topic:
Clinical and Translational Medicine 11, e562 (2021) - Used integrative multi-omics network analysis to decode exposure-linked lung injury mechanisms, establishing our cohort-to-mechanism pipeline for environmental immune perturbations.
Environmental Pollution. 366, 125471 (2024) - Connected prenatal particulate exposure to childhood allergic disease through placental/cord multi-omics, supporting an exposure-to-immune-programming framework.
Selected papers from our lab on this topic:
Clinical and Translational Medicine 11, e562 (2021) - Used integrative multi-omics network analysis to decode exposure-linked lung injury mechanisms, establishing our cohort-to-mechanism pipeline for environmental immune perturbations.
Environmental Pollution. 366, 125471 (2024) - Connected prenatal particulate exposure to childhood allergic disease through placental/cord multi-omics, supporting an exposure-to-immune-programming framework.
Nature Reviews Immnology. 23, 74-89 (2023)
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