Dr. Yejing Ge
The University of Texas MD Anderson Cancer Center
Department of Cancer Biology
Adult stem cells (SCs) are essential units 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 developmental biology, 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, abundant, and genetically tractable. Squamous cell carcinomas (SCCs) of skin highly resemble those deadly cancers in head and neck, esophagus, lung and cervix. Studying skin SCCs, we found SCs adopt a plastic phenotype so called “lineage infidelity”, entailing a wide spread co-expression of otherwise lineage restricted genes. Our most recent observations suggest lineage infidelity occurs across many diseases and stress conditions including aging and chronic wounds, therefore may represent a core mechanism SCs use to steer fate choices and valuable therapeutic target in human patients.
A few potential rotation projects are:
- Determine functional targets and molecular mechanisms of key lineage infidelity transcription factors in driving squamous cell carcinomas progression
- Investigate epigenetic determinants of lineage infidelity during hair follicle stem cell aging
- Screen novel non-coding drivers of human squamous cell carcinomas using functional genomic approaches and explore therapeutic opportunities