Research & Clinical Summary

Pancreatic cancer is one of the most lethal of all human malignancies, responsible for hundreds of thousands of deaths annually. Combination chemotherapy remains the standard of care for patients with pancreatic cancer, which continues to carry a prognosis of less than one year. Thus, there is an urgent need to improve our understanding of pancreatic cancer pathogenesis and to leverage that understanding toward better therapeutic options.

As with all eukaryotic cells, the DNA double helix in the pancreatic cancer cell nuclei is packaged around histones into a highly condensed, higher order structure called chromatin. In order for eukaryotic cells to undergo transcription, replication and DNA repair they have to overcome this natural barrier to DNA accessibility. However, cancer cells frequently dysregulate these normal processes as an exquisite mechanism to gain the plasticity needed to achieve uncontrollable growth and survival.

Our laboratory uses genetically-engineered mouse models, patient-derived cell lines and clinical pancreatic cancer samples to investigate the role of chromatin modifying proteins in the formation, progression and spread of pancreatic cancer. We study how the dysregulation of these proteins may enhance tumor cell plasticity and allow tumor cells to both survive and adapt to the harsh conditions in the tumor microenvironment. As part of this work, we would like to explore whether acquired drug resistance is driven by epigenetic plasticity and if we can use this information to identify novel drug targets.

A second area of focus in the lab is on developmental pathways in pancreatic cancer. We have found that a more aggressive subset of pancreatic cancer hijacks genes that are specifically expressed in early development but are subsequently silenced during differentiation and maturation of the organism. We would like to explore how these “oncofetal” proteins drive tumor cell growth and survival and whether they are necessary and sufficient for pancreatic cancer formation, progression and metastasis.

These avenues of exploration will not only identify relevant molecular subsets of pancreatic cancer for improved prognosis and stratification of patients toward a more effective therapy but will also help us create novel therapeutic strategies in this lethal disease.


More publications associated with this author on PubMed

The following publications were retrieved from PubMed:

2005Kugel, Sita

More publications associated with this author on PubMed