Epigenetic plasticity in pancreatic tumor initiation 

Through careful epigenomic profiling of the exocrine acinar cell as it undergoes transdifferentiation to a 'duct-like' state and neoplastic conversion, we are identifying the perturbations to the epigenome that are central to tumor initiation

 
 
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Tumor-suppressive mechanisms in the acinar cell

In vivo, oncogenic stress or an inflammatory insult are not sufficient alone to 'lock-in' the metaplastic state whereby the pancreatic acinar cell becomes duct-like. Characterization of the underlying chromatin reveal the means by which the acinar cell maintains its identity via mechanisms that stabilize its epigenetic landscape.

 
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Cooperativity between Kras activation and inflammation

Together, activation of the key driver oncogene in pancreatic cancer (Kras) and inflammation are sufficient to drive neoplastic conversion in normal acinar cells. This conversion results in not only massive histologic and transcriptional change, but widespread dysregulation of the epigenome. We are currently characterizing the precise means by which this chromatin alteration enables tumorigenesis.