Perelman School of Medicine at the University of Pennsylvania

Capell Lab

banner image

EPITHELIAL EPIGENETICS

Epithelial tissues rely on a highly coordinated balance between self-renewal, proliferation, and differentiation. Epigenetic mechanisms provide this precise control through the regulation of gene expression in order to establish and maintain cell fate and identity. Disruption of these pathways can disrupt diverse cellular processes including both metabolism and immunity, and ultimately drive diseases such as cancer. 

Consistent with this, chromatin modifiers and modifications are commonly dysregulated in diseases ranging from developmental disorders to age-related diseases such as cancer. For example, there is an exceptionally high incidence of mutations in epigenetic modifiers in cancers of self-renewing epithelial tissues such as squamous cell carcinoma (SCC). SCC is the most common type of cancer worldwide, affecting numerous epithelial tissues ranging from the skin and eyes to the lung, esophagus, and oropharynx. Despite this, precisely how disruption of epigenetic homeostasis may drive epithelial cancers such as SCC is poorly understood. 

In the Capell Lab, we combine cutting-edge epigenetic technologies, human patient samples, primary cells, and mouse models in order to solve fundamental unanswered questions:

- How are epigenetic processes (histone, RNA, DNA) impacted by intrinsic (i.e. aging, sex chromosomes) and extrinsic (i.e. ultraviolet radiation, diet, etc.) environmental influences, and how do these changes impact cellular homeostasis (i.e. metabolism, immunity) to promote epithelial diseases such as cancer? 

- By elucidating these mechanisms, can we identify new targets and therapeutic vulnerabilities for the prevention and treatment of these potentially deadly conditions?

If you would be interested in joining our team, please contact us!