Perelman School of Medicine at the University of Pennsylvania

Capell Lab

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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 enhancer and transcriptional networks that establish and maintain cell fate and identity. Disruption of these pathways can lead to a loss of proliferative control, ultimately driving cancer. 

Consistent with this, chromatin regulators are amongst the most frequently mutated genes in all of cancer, with an exceptionally high incidence of mutations 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 several fundamental unanswered questions:

  • How is the skin epigenome altered by intrinsic (i.e. aging) and extrinsic (i.e. ultraviolet radiation) environmental influences, and how do these changes contribute to disease?  
  • How do chromatin regulatory enzymes function in both normal and diseased skin, particularly during carcinogenesis?  
  • Can we target the epigenome with precision to treat disease?

Through this, we hope to identify new epigenetic targets for prevention and treatment of these potentially deadly cancers.

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