NTU Bio-Tech

Associate Professor Shu-Han Yu’s Laboratory (The S.H.Y. Lab) focuses on two major research areas: the tumor immune microenvironment (TIME) and personalized medicine. The laboratory integrates high-throughput spatial transcriptomics with AI-guided multiplex immunohistochemistry to investigate the spatial organization and cellular interaction patterns within the tumor microenvironment. Through this platform, the lab aims to reconstruct functionally relevant immune microdomains, or immuno-clustering patterns, within the TME and further analyze the spatial proximity and interactions among different cell populations in these regions, enabling high-resolution spatial biology research.


The tumor immune microenvironment consists of tumor cells, tumor-infiltrating immune cells, cancer-associated fibroblasts, tumor vasculature, and extracellular matrix components. Together, these cellular and non-cellular elements regulate tumor immune evasion, promote tumor growth and metastasis, and influence patient responses to therapy. Therefore, systematic analysis of the immune cell composition and spatial distribution in patient tumor tissues and surrounding tissues can help establish a standardized platform for TIME analysis and further support the development of precision medicine and personalized therapeutic strategies.


The tumor microenvironment research platform established by Dr. Yu’s laboratory can be applied to the investigation of tumor biology and therapeutic mechanisms in canine and feline cancers, as well as other disease models. This platform is also integrated into the laboratory’s long-standing research on oral squamous cell carcinoma (OSCC). By analyzing the spatial organization of the tumor immune microenvironment and immune cell interaction patterns in OSCC patient tissues, the lab aims to evaluate their potential as predictive indicators of immunotherapy response. These research outcomes may help clinicians develop more precise personalized diagnostic and treatment strategies based on the unique TIME features of each patient, thereby reducing unnecessary drug use and treatment costs while minimizing potential side effects associated with high-dose, long-term, or continuous medication.

Idiopathic pulmonary fibrosis (IPF) is clinically characterized by a high mortality rate and currently remains incurable. Although pan-histone deacetylase (pan-HDAC) inhibitors have demonstrated potential in slowing disease progression, their lack of selectivity often leads to severe adverse effects, such as hepatotoxicity and skin toxicity. To address this clinical bottleneck, this study collaborates with Professor Chao-Wu Yu’s team from the School of Pharmacy at our university. We have successfully designed and synthesized a series of novel, selective inhibitors targeting HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, or dual HDAC6/8, aiming to minimize off-target effects and enhance therapeutic safety through precise epigenetic regulation.

To efficiently identify candidates with clinical potential, our team established an innovative three-stage drug screening platform to systematically accelerate drug development and reduce costs.

• In the first stage, mouse embryonic fibroblasts (NIH-3T3) were utilized for initial pre-screening against TGF-β1-induced fibrosis, successfully identifying hit compounds from the small-molecule library.

• In the second stage, human pulmonary fibroblasts (HPF) were employed for further efficacy validation, integrated with early drug metabolism and pharmacokinetics (DMPK) evaluations—specifically Caco-2 cell permeability and liver microsomal stability assays—to precisely narrow down the pool to the final two lead compounds possessing high stability and permeability.

• In the third stage, a molecular docking approach and a bleomycin-induced pulmonary fibrosis mouse modelwere implemented for in vivo validation of these lead compounds.

Our findings demonstrate that the identified key lead compounds significantly inhibit TGF-β1-induced proliferation of pulmonary fibroblasts and effectively downregulate the expression of fibrosis-associated proteins, thereby mitigating the progression of pulmonary fibrosis in mouse models. This comprehensive drug discovery pipeline—which seamlessly integrates chemical synthesis, multi-stage in vitro efficacy and pharmacokinetic screening, and in vivo disease model validation—lays a critical foundation for applying selective HDAC inhibitors to anti-fibrotic therapies. Looking forward, it holds great promise for developing highly effective, non-toxic, and innovative targeted drugs, ultimately improving the quality of life for patients suffering from IPF.