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Grant Abstract: Mechanisms of Carotenoid Transport and Interactions with Nutrient Absorption

Grant Number: 1K99AT008576-01A1
PI Name: Moran
Project Title: Mechanisms of Carotenoid Transport and Interactions with Nutrient Absorption

Abstract: PROJECT SUMMARY Candidate: I am a trained, translational nutrition scientist focused on studying the complex genetic and nutritional factors impacting physiological responses to diet. With a foundation in Molecular and Cellular Biology and Chemistry, during Nutritional Sciences PhD training I developed a paradigm for stable- and radio- isotope-labeled tomato carotenoid production and studied tomato carotenoid distribution in animals. During postdoctoral training, I utilized these tracers to find that human kinetic responses to the red tomato carotenoid, lycopene (LYC) (associated with a reduced risk of several chronic diseases and malignancies), vary widely. Furthermore, I found the kinetics and biodistribution of LYC and the structurally similar, potentially bioactive tomato carotenoid, phytoene (PE), to differ markedly in humans and rodents. Research: To understand the mechanistic causes of heterogeneous responses to diet, I propose to study how interactions between PE and LYC with candidate membrane transport proteins dictate systemic carotenoid exposure. Aim 1. To determine if intestinal and prostatic uptake and efflux of PE and LYC is mediated by candidate lipid transporters (SCARB1, CD36, or ABCA1) in vitro. Aim 2. To define the regulatory roles of lipid transporters in LYC and PE systemic exposure in vivo. Aim 3. To determine if and how LYC or PE impact uptake and systemic exposure of two phytonutrients which are known to be transported by SCARB1 & CD36: ß-carotene and a-tocopherol. Research career development plan: The proposed training plan will provide the tools and experience needed to expand my current research efforts to address nutrigenetic mechanisms. The co-mentors are leaders in translational nutrition research for disease prevention and carotenoid nutritional biochemistry. In addition, an advisory committee of professors from Pharmacology, Food Science & Technology, and Medical Genetics will meet semi-annually to evaluate my training and research progress and my preparation to transition to a tenure- track position. Environment: The Ohio State University and Wexner Medical Center is a hub of interdisciplinary nutrition and disease prevention research. OSU’s “Crops to the Clinic” program promotes an interdisciplinary program in which plant scientists, food scientists, basic and applied nutritionists, epidemiologists, and physicians collaborate to study dietary compounds and functional foods. Long-term career goals: My long-term goals are to A) establish an academic lab at a research university to conduct cutting-edge studies of dietary bioactive compound nutrigenetics and bioactivities, to B) train future leaders in the field of nutritional dietary bioactives, and to C) promote rigorous investigations of dietary phytochemicals for evidence-based recommendations on diet and supplement use. Impact: By understanding nutrigenetic factors impacting the response to diet, we will better design clinical trials and develop public health diet and supplement use recommendations to maximize benefits and minimize risks. The proposal plan will yield a highly trained, interdisciplinary, translational nutrition scientist who is uniquely prepared to meet this challenge. PUBLIC HEALTH RELEVANCE: Population studies indicate that people with higher levels of blood lycopene, the red carotenoid pigment in tomatoes, have a lower risk of stroke, heart attacks, and several cancers including that of the prostate. However, individuals vary in their response to dietary tomato lycopene, making it challenging for nutritionists to recommend a specific amount of tomato that should be eaten to lower disease risk. This study will focus on understanding the genetic and nutritional factors that impact the response to dietary tomato carotenoids, so that nutritionists and health care providers can better develop customized dietary recommendations to promote health.

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