A major effort in the Kuperwasser Lab is to define the cellular precursors to human breast cancers and uncover how mutations or stable epigenetic changes sustained in these cells affect cell fate decisions and cellular plasticity to create heterogeneous tumor phenotypes. Efforts have been focused on uncovering the transcriptional mediators for somatic cell plasticity including transcription factors, chromatin modifiers as well as factors that post-translationally modify these factors (eg. SLUG/SNAI2, TAZ/WWTR1,TBX3 etc). This work has revealed fundamental mechanisms that regulate normal and cancer stem-like states as well as how these factors might be exploited to contribute to metastasis.
Other ongoing interests and projects relating to this include:
- Identifying breast tissue hierarchy, stem cells, and factors that control cellular plasticity and tissue development
- How mutations reprogram cell identity
- Understanding the effects of aging on stem cell fitness
- Reconstructing human breast tissues in vivo