Elucidate the genetic and epigenetic regulation during mammalian stem cell development and tumorigenesis, and how stem cells or tumor cells communicate with their microenvironment.

1. Mammalian spermatogonial stem cells (SSCs)
- Identified the essential role of Spry4–ERK signaling in initiating adult mouse SSCs recovery and sustaining fertility following chemotherapy-induced damage in male reproduction system.
- Developing a three-dimensional semi-physiological culture platform to expand human reproductive tissues in vitro, including SSCs, testicular seminiferous tubules, normal prostate or prostate cancer (PCa) organoids.
- Histone variant H3.3 functions in mammalian SSC homeostasis and germline development 

2. Tumor microenvironment (TME)
- Developing a three-dimensional vascularized tumor organoid culture platform “Tumor-On–VascularNet” with stable blood and nutrient transportation to predict chemoimmunotherapy efficacy in esophageal adenocarcinoma (EAC) patients. 
- Reconstituting tumor microenvironment in vitro with engineered human vascular endothelial cells (R-VECs) and immune cells (macrophages, neutrophils, etc.) to investigate therapy resistance and epigenetic reprogramming within tumor organoids and tumor-associated cells.
- Identifying novel epigenetic targets or biomarkers to improve chemoimmunotherapy efficacy with angiogenesis facilitated tumor organoid culture.
- Optimizing a novel circulating tumor cells (CTCs) culture protocol for patients with metastatic breast cancer or colon cancer using R-VECs and microfluidic enrichment.