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Grant Abstract

Grant Number: 5P50AT006273-03
PI Name: Lubahn
Project Title: MU Center for Botanical Interaction Studies

Abstract: DESCRIPTION (provided by applicant): Botanicals are capable of interacting with several cell regulating pathways at the same time. Our Center's goal is to explore the crosstalk between antioxidant-related pathways. The 5 key pathways to be examined are the (anti)oxidant (Nrf2/Keap1 and NADPH oxidase) pathways and their interactions with the NF-kappaB-, estrogen-, and hedgehog-signaling pathways. Research Project 1: Botanicals Targeting 5 Signaling Pathways to Prevent Prostate Cancer will test the hypothesis that five individual, widely-used botanical dietary supplements will prevent prostate cancer through the five key signaling pathways. Research Proiect 2: Botanical Phenolics on Oxidative/Nitrosative Signaling Pathways: Implication for Cerebral Ischemia will test the hypothesis that botanicals promote brain health and prevent neurodegeneration through modulating the NADPH oxidase-, Nrf2/Keap1-, and/or NF-kappaB-signaling pathways, and protein modifications by S-nitrosylation. Research Project 3: Antioxidant Botanicals and Antimicrobial Defenses will test the hypothesis that botanical compounds that possess potent antioxidant activity modulate cellular events associated with antimicrobial defense. The Center includes five core facilities. The Administrative Core will oversee the Center's research, training, and pilot programs. Core A: Botanicals/Plant Genomics Core will identify, cultivate, and document raw plant materials including novel cultivars of elderberry and soy. Core B: Nutrition/Animal Core will provide transgenic mice and prepare diets for the research projects. Core C: Analytical Chemistry Core will provide analytical support and quality control for quantifying botanical compounds and their metabolites, and verifying plant material. Core D: Interactions Core: Mega-sequencing/Proteomics/lnformatics/Nitrosylation) will provide novel technology for proteomic and nitrosylation analyses, DNA mega-sequencing for mRNA analysis, and data integration through bioinformatics and statistical support. MU is highly supportive of this Center and is providing funds to train and support four graduate research assistants. Pilot projects will help provide seed money for new botanical grants and allow career development of both new faculty and students. Our Center's approach using bioinformatics to explore 5 signaling pathways concurrently by the latest cutting edge technology in mRNA and protein analysis is highly innovative. This type of synergism, when combined with the botanical and pathway expertise of Center investigators, will generate new information important in human health. PUBLIC HEALTH RELEVANCE: The botanicals we propose to study are already extensively used by the public, and though they have antioxidant properties that may offer cancer, immuno-, and neuroprotective effects, the molecular basis of these effects is largely not understood. Our overall goal is to test and identify botanicals and related molecular mechanisms that can potentially offer beneficial effects to maintain a healthy body and brain by preventing neurodegenerative and infectious diseases, as well as cancer.

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