Grant Abstract: A Revitalized Framework for Vitamin Biology: New Sensors, Pathways and Precision Therapies

Grant Number: 1R01AT013724-01
PI Name: Jain
Project Title: A Revitalized Framework for Vitamin Biology: New Sensors, Pathways and Precision Therapies

Abstract: Our research project seeks to fundamentally transform the field of vitamin biology by applying modern scientific approaches to uncover the critical roles that vitamins play in health and disease. Although vitamin supplementation is widely recognized for its practicality and safety, it is often used without a strong scientific basis. To address this, we aim to systematically identify all enzymes and metabolic pathways that depend on each vitamin cofactor using advanced techniques like thermal stability proteomics and gradient metabolomics. Additionally, we will explore the body's ability to sense and respond to varying vitamin levels by identifying novel vitamin sensors and their associated signaling pathways. These discoveries could open new avenues for targeted therapies, much like the breakthroughs made in understanding other metabolic sensors. Furthermore, we will investigate the potential of megavitamin therapies by identifying genetic diseases that can be ameliorated with high doses of specific vitamins. Through genome-wide CRISPR screens and in- depth phenotyping of relevant mouse models, we aim to pinpoint conditions that respond favorably to vitamin supplementation. This approach has already shown promise in our preliminary work with vitamin B3 and the genetic disorder NAXD, where we observed a dramatic extension of lifespan. By expanding this strategy across all vitamins, our work could lead to immediate and impactful therapies for a wide range of genetic disorders, offering a new era of personalized vitamin-based treatments. PUBLIC HEALTH RELEVANCE: Our proposed research seeks to revitalize the field of vitamin biology using modern approaches. We aim to identify all enzymes and metabolic pathways dependent on vitamins, discover new vitamin sensors that regulate essential biological processes, and pinpoint genetic diseases that can be treated with megavitamin therapies. By leveraging modern techniques, we hope to revive and expand the understanding of vitamin metabolism, leading to personalized vitamin-based treatments and potentially instant cures for numerous genetic disorders.

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