Research & Initiatives
Our research program integrates several different model systems for our research investigations, including tissue culture models derived from the patients we treat, commercial cell lines, mouse models of pancreatic cancer, and a clinical data with a complementary biologic tissue repository. We seek to understand how pancreatic cancers develop resistance to standard chemotherapies. Additionally, we are interested in understanding how pancreatic cancer is able to successfully adapt to the extremely harsh metabolic conditions that are present throughout the tumor microenvironment such as hypoxia and low nutrient levels. Our aim is to design therapies that specifically target these adaptive mechanisms.
IDH1
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Research
Pancreatic cancer cells are poorly perfused, and live in a particularly harsh microenvironment characterized by low nutrient and oxygen levels. Normal cells, however, are well perfused and therefore have abundant nutrient availability. We are studying the molecular mechanisms that allow pancreatic cancer cells to adapt low nutrient conditions. Through investigations in tissue culture and mouse models of pancreatic cancer, we have shown that a regulatory molecule, HuR, supports pancreatic cancer survival under harsh conditions, and this is largely due to its regulation of the metabolic enzyme, isocitrate dehydrogenase (IDH1). We are interested in developing novel therapies that target this molecular interaction in order to render pancreatic cancer cells susceptible to stressful metabolic conditions. Mitochondria function is also especially important under low nutrient conditions and we seek to target this metabolic vulnerability in pancreatic cancer. We have received funding from the American Cancer Society and the NCI to pursue these lines of investigation.
Ketogenic Diet
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Research
Our goal for this project is to understand the effect of a ketogenic diet on pancreatic cancer metabolism and epigenetic. We believe a ketogenic diet exacerbate the hypo-nutrient environment of pancreatic cancer which up-regulates the oxidative stress. This environment provides a better opportunity for the small molecular inhibitors and chemotherapy to be more effective. On the other hand, ketone bodies are known HDAC inhibitors and they have potential to up-regulate the expression of anti-tumorigenic genes. Our lab soars to investigate whether a ketogenic diet can increase the efficacy of FDA approved HDAC inhibitors that failed in clinical trial against pancreatic cancer.
Immune Therapy
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Research
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Clinical
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Combination Therapy
Pancreatic Cancer-associated Depression & Weight Loss
Depression is more common in cancer than the general population, and amongst cancers, is the most common in pancreatic cancer. We will perform a randomized trial in patients with pancreatic cancer and randomized patients to an anti-depressant or placebo in order to try and reduce depression. Additionally, we study the biology of pancreatic cancer-associated depression, and believe it is directly related to increased tryptophan catabolism.
