Major Projects
1. Mechanisms of invasion and metastasis in pancreatic cancer. We have identified a novel pancreatic cancer biomarker: carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6). We have shown that over 90% of human pancreatic adenocarcinomas overexpress CEACAM6 and that tumoral CEACAM6 expression level is inversely correlated with survival duration following surgical resection of pancreatic adenocarcinomas (Figure 1). We have also shown that CEACAM6 is a key determinant of pancreatic cancer cellular invasiveness, anoikis-resistance, and metastasis. Mechanistic studies focus on characterizing downstream effectors and upstream regulators of CEACAM6 signaling.
2. Systemic siRNA-mediated gene silencing: a new approach to the targeted therapy of cancer. RNA interference (RNAi), mediated by small interfering RNA (siRNA) silences genes with a high degree of specificity and potentially represents a general approach for molecularly targeted anticancer therapy. We have recently demonstrated the efficacy of systemically-delivered siRNA in inducing specific gene silencing in vivo using a preclinical model of pancreatic cancer. In one example, systemic delivery of siRNA targeting CEACAM6 resulted in an inhibition of tumor growth (Figure 2) and improved survival (Figure 3) in a nude mouse xenograft model of pancreatic cancer.
3. Mechanisms of chemoresistance in pancreatic cancer. This project focuses on identifying new mechanisms of chemoresistance, particularly those related to gemcitabine, the principal chemotherapeutic agent used in the treatment of advanced pancreatic cancer. We have shown that siRNA-mediated silencing of CEACAM6, c-Src, and ribonucleotide reductase M2 subunit (RRM2) each increases the anticancer efficacy of gemcitabine.
4. Intestinal regeneration and tissue engineering. This project is designed to develop methods for expanding intestinal absorptive surface area as a strategy for treating patients with short bowel syndrome. Previously, in collaboration with Drs. Steve Secor and Jared Diamond, we characterized the mechanisms of intestinal adaptation in the Burmese python, a species which exhibits meal-induced increases in intestinal mass and absorptive capacity to an extreme degree (Figure 4). Currently, in collaboration with Dr. Joseph Vacanti, we are developing strategies for optimizing form, function, and resilience in a tissue-engineered intestine prototype (Figure 5).
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