RESEARCH INTERESTS
The Pancreas
Bardeesy N and DePinho R A. (2002)
The pancreas is like a tree with branches (ducts) and leaves (acini), as well as a birds nests (endocrine cells).
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The pancreas has both an endocrine and exocrine function. The hormone producing endocrine cells of the pancreas are located in nests called the islets of Langerhans and they are instrumental in controlling blood glucose homeostasis. Loss of beta cells, which produce the hormone insulin, leads to the onset of Type I Diabetes.
Exocrine function is controlled by acinar cells and ductal cells. These cells are arranged in a manner similar to a tree with the tree trunk being comprised of tube forming ductal cells and acinar cells representing the tree leaves. Together these cells combine to produce digestive enzymes and a stomach acid neutralizing solution that is delivered into the duodenum to aid in food digestion. Islets are nestled in the branches of the tree like nests. |
Pancreatic Cancer
Pancreatic Cancer will be diagnosed in 4700 Canadians this year alone, and 92% of these patients will die within 5 years, 75% within the first year. Pancreatic ductal adenocarcinoma is the most common type of pancreatic cancer and it often called a "silent" killer because it is initiated and progresses to a disseminated disease in the absence of recognizable symptoms. While treatment with chemotherapy is recommended for patients with early stage disease, patients are not often cured by these treatments. Our efforts to improve patient outcomes are focused on understanding 1) how this disease develops in order to improve our ability to detect this deadly cancer earlier and 2) how early events in tumour initiation affect tumour biology.
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Stained image showing ductal adenocarcinoma
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Chuvin, N, et al. 2017
Tools
To examine the cellular and molecular mechanisms underlying the development of pancreatic diseases, we are focused on understanding how specialized cell types of the pancreas are formed and how they contribute to diseases. To do this, we utilize mice to study pancreatic development and model aspects of pancreatic disease.
In addition to working with mice, we use tissue culture to continue to expand our understanding of the relationship between pancreatic and immune cells during tumor initiation. |
Projects
How does cellular origin impact pancreatic ductal adenocarcinoma (PDA)?
Diagram modelling how each cell type contributes to ductal adenocarcinoma through a ductal cell lineage
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Studies in mice have shown that acinar cells can give rise to ductal adenocarcinoma, but it is unclear what role ductal cells have in the initiation of the disease. Thus far, it has not been possible to address this issue, but we have developed mouse models that induce cancer initiating mutations in each cell type to address this open question and examine how each cell type affects the biology of pancreatic ductal adenocarcinoma. |
What are the molecular mechanisms underlying the initiation of different precancerous lesions?
Three different precancerous, or precursor, lesions are thought to precede the formation of pancreatic cancer. Whole genome sequencing of these lesions have provided insights into the mutations that are associated with the disease, but it is unclear what role these mutations have in that initiation and progression of each lesion, particularly the large cystic intraductal papillary mucinous neoplasia lesions (IPMN). We recently developed a mouse model of IPMN and we will utilize this unique model to examine the impact of these human gene mutations on IPMN development.
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How do the mechanisms regulating cell proliferation and differentiation differ between specialized pancreatic cell types?
Immunofluorescent staining highlighting embryonic pancreas structure
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Pancreatic ductal cells not only provide a conduit for acinar-cell-derived digestive enzymes, but they also create the structural foundation of the entire pancreas. However, it is unclear how proliferation of normal ductal cells are controlled during development to create the proper sized organ. Our initial studies examining the mechanisms regulating proliferation and differentiation in the pancreas will focus on several candidate genes identified by gene expression microarray analysis that may be involved in regulating proliferation and differentiation of ductal cells.
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