Sugar, PI3K, and Cancer

The uncontrolled cellular growth that characterizes tumor formation requires a constant delivery of nutrients.  For over a century, researchers have wondered if the supply of nutrients from the diet could impact tumor development.  In these projects, our goal is to assess if dietary sugar can directly or indirectly (via insulin) stimulate tumor growth.

1. The Effects of Fructose on Tumor Growth and Metabolism

Tumors that form in the colon and liver come in direct contact with glucose and fructose from the diet. Here, we are interested in examining the effects of glucose, fructose, and the combination of the two on tumor metabolism and growth.

Active Grants:

National Cancer Institute (R01), Molecular Mechanisms of Fructose-induced Colorectal Cancer Cell Survival. PI, 09/01/2021 – 08/31/2026. $3,387,755.

Prior Grants:

Pilot Project, Developmental Research Program, WCM SPORE in Prostate Cancer (P50), The Role of Fructose Metabolism in Prostate Cancer Growth and Development, PI, 08/01/19-07/31/20. $75,000

2. The Effects of Fructose on Intestinal Villous Length, Nutrient Uptake, and Obesity.

Fructose is ubiquitous and unavoidable in the food we eat. It is critical that we understand how it is altering our metabolism. We found that fructose metabolites can change cell metabolism and elongate the intestinal villi. In this project, we are studying the effects of fructose on intestinal architecture and lipid transport.

Pending Grants:

National Institute of Diabetes and Digestive and Kidney Diseases (R01), The role of PKM2 in dietary lipid absorption and fructose-induced obesity. PI, 04/01/2022 – 03/31/2027. $3,092,692.

3. The Effects of Insulin and PI3K on Uterine Cancer Growth and Metabolism

High insulin has been directly implicated in the pathogenesis of uterine (endometrial) cancer. Insulin stimulates PI3K to drive cell growth, proliferation, and anti-apoptotic pathways. Here, we will take a rigorous, translational approach using longitudinal biospecimens from clinical trials and patient-derived organoid mouse models to validate the effectiveness of lowering insulin and blocking PI3K.

Active Grants:

AACR-The Mark Foundation for Cancer Research “Science of the Patient” Grant, Targeting Insulin to Improve Endometrial Cancer, PI, 12/15/2020-12/14/2023. $750,000

Prior Grants:

CTSC Pilot Award, A Feasibility Study Evaluating the Effects of Ketogenic Diet in Endometrial Cancer, Co-PI, 01/18/18-01/20/20, $100,000