Over my career, I’ve studied the physiology and molecular biology of mineral metabolism, especially the role that vitamin D plays in the regulation of intestinal calcium absorption.

See   Xue et al. (2009) Gastroenterology

  Cui et al. (2012) J Bone Min Res.

More recently I have conducted studies to determine the role of natural genetic variation on bone and mineral metabolism.   Initially I worked with clinicians to assess the impact of polymorphisms in candidate genes (most notably the VDR) on bone-related disease. However, in the last 10 years I have conducted studies using mouse genetics.   This work is demonstrating that genetics and diet interact to influence physiology.  Broadly speaking, these studies are essential proof of principle for the concept of a biological basis for personalized nutrition.

A schematic of our approach to studying Gene x Diet interactions in mouse models.  Mapping phenotypes for bone and calcium metabolism affected by natural genetic variation identifies loci controlling those traits.   Some genetic influences are not affected by changes in diet but others appear and disappear depending on the diet fed.   In addition, some loci reflect the physiologic adaptation to the dietary change and these are different from the loci that control the basal phenotype.  Once loci are found we do additional informatic and experimental studies to identify the affected gene and test the function of the gene in cells and mice.

Genetically Programmed High Bone Mass Changes Calcium Metabolism.  Classically, calcium metabolism is thought managed to keep serum calcium in a very narrow range.   When dietary Ca is low, the body adapts by increasing the efficiency of calcium absorption, promoting calcium reabsorption from the kidney, and mobilizing bone calcium stores.  However, in mice with a genetic mutation that promotes high bone formation (a mutant form of the Wnt receptor Lrp5), high bone mass appear to be driving changes in calcium metabolism to maintain higher serum calcium through improved calcium absorption and renal calcium reabsorption.  This higher serum calcium provides more calcium to mineralize the newly formed bone.   Interestingly this all seems to be done without the need to increase the production of the active vitamin D metabolite (and regulator of calcium absorption), 1,25(OH)2 D.