Adult stem cells (SCs) undergo long-term self-renewal and multi-lineage differentiation to orchestrate postnatal remodeling and repair damage. In contrast to steady state, SCs in coping with stress often expand their fates and embark on behaviors distinct from their homeostatic patterns, known as plasticity. While plasticity is essential for organismal survival, its derailed regulation poses disease vulnerability to individuals, especially those undergoing prolonged stress. Under these scenarios, SCs are subjected to functional exhaustion frequently observed in aging, or malignant transformation that occurs in cancer.
Research in the Ge lab applies principle of development biology and genetics, aiming to understand molecular mechanisms underlying SC plasticity, and how its deregulation leads to human diseases. One of the key hypotheses we set out to test is this long-postulated idea “cancer is a wound that never heals”. Parallels between wounds and cancer have emerged in many contexts, begging questions in regards to their molecular origin and functional relevance.
Mouse skin represents an excellent model to address these outstanding issues. Its SCs are well defined, accessible, abundant, and genetically tractable. Squamous cell carcinomas (SCCs) of skin highly resemble those in head and neck, esophagus, lung and cervix. There, we identified a SC plasticity phenotype known as “lineage infidelity”, entailing a wide spread co-expression of otherwise lineage restricted genes. Lineage infidelity is functionally required for wound repair and cancer, and potentially other diseases and stress conditions. Therefore, it may represent a core mechanism that SCs employ to steer fate choices and a valuable therapeutic target in human patients.
Our lab’s ultrasound-guided in utero lentiviral microinjections achieves rapid, stable and skin specific transgene integration, which enables functional genomics at a hitherto unparalleled speed and precision. Our long-term goal is to leverage the basic knowledge we learn from human data and mouse models to therapeutically benefit patients with degenerative and malignant diseases.