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Grant Abstract: Vitamin D and HA Signaling in TNBC

Grant Number: 5R01CA194500-03
PI Name: Welsh
Project Title: Vitamin D and HA Signaling in TNBC

Abstract: This supplement will expand the studies described in the parent R01 through direct analysis of tissue vitamin D metabolites in tumor bearing animals. Published data on tissue vitamin D stores is extremely limited. However, identification of the cellular pathways that regulate flux between the physiological vitamin D pools in the body is critical to understanding the considerable variability in human serum 25D levels after oral dosing as well as the differences between populations and in diseases states (i.e. obesity, cancer, diabetes). A number of strategies are available for vitamin D supplementation in populations at risk for deficiency, including large bolus doses given weekly, monthly or quarterly. Although the intention with bolus doses is to fill tissue reserves, it is currently unclear how the body handles such large doses, and whether tissue rese3rves can be mobilized when needed. It is highly likely that genetic, physiologic and environmental factors interact to regulate tissue vitamin D reserves and how they are utilized. This small scale project is designed to assess tissue vitamin D3 stores in relation to environment (dietary vitamin D3), genetics (presence or absence of DBP) and disease (breast cancer) in mouse models. We anticipate these studies will generate important preliminary data leading to more comprehensive projects to define genes, pathways and mechanisms by which tissue vitamin D stores are regulated.

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