Human Nutrition Research Center on Aging - Tufts University
- Rapid screening method for low calcium absorption in humans. Determine to what extent a stable strontium oral absorption test can be used as a surrogate measure to estimate calcium absorption and successfully identify persons with poor vitamin D-induced calcium absorption.
- The FokI vitamin D receptor polymorphism reduces vitamin D-mediated intestinal calcium absorption and gene expression in elderly men and women. Aging imposes an added stress on maintaining calcium homeostasis. We hypothesize that elderly persons with the Ff and ff Fok I vitamin D receptor polymorphism also have an additional burden because of a weakened vitamin D cellular response in the enterocyte due to the presence of a less efficient elongated form of the vitamin D receptor protein that results in reduced vitamin D-mediated intestinal calcium absorption on a low calcium diet.
- Rate Limiting Molecular Determinants of Intestinal Calcium Transport. Determination as to whether TRPV6 (CAT1), an epithelial calcium channel, or calbindin D, intracellular calcium binding protein, expression will be knocked out by RNA interference techniques in Caco-2 cells to assess the role of these proteins in calcium transport.
- Extracellular Calcium Sensing Receptor Mediates the Chemoprotective Effects of a High Calcium Diet on Colon Cancer. Evaluation of the effects of a high calcium diet on carcinogen-induced colon carcinogenesis in PTH-extracellular calcium-sensing receptor double knockout mice.
- Heat Shock Protein 90 is Necessary for Vitamin D Signaling. Our recent studies using RNA interference have implicated HSP90 as a novel and important mediator of vitamin D-induced gene expression. Our current studies are focused on determining whether HSP90 binds directly to the vitamin D receptor in the cytosol and mediates vitamin D bioavailability by controlling access to the vitamin D receptor ligand-binding pocket.
- TRPV6/CAT1 Epithelial Calcium Channel Modulates the Rapid Non-genomic Cellular Response to Vitamin D. Rapid membrane-initiated cell signaling alters intracellular calcium concentrations. These studies are testing the hypothesis that the extent of the rapid rise in intracellular calcium in response to vitamin D is determined by the membrane TRPV6 channel.
- Conjugated Linoleic Acid (CLA) Enhances Calcium Bioavailability. CLA is a potential functional food component that may have positive effects on intestinal calcium absorption, as well as antidiabetic and anticarcinogenic actions. We hypothesize that the positive biological effects of CLA on the gut are mediated via its action as a ligand for the peroxisome proliferator-activated receptor. This hypothesis is currently being tested in Caco-2 cells, a human intestinal cell line.