Diane R. Dowd, Ph.D.
Assistant Professor of Pharmacology
Phone: (216) 368-4076
Fax: (216) 368-3395
E-mail: diane.dowd@case.edu
Wood W-334
Research
The proper development and maintenance of bone is controlled by a number mechanisms. Vitamin D (Vit D) and calcium are two players in the complex regulation of bone development. The biological effects of Vit D are mediated through a nuclear protein termed the vitamin D receptor, or VDR. As a member of the superfamily of nuclear receptors, the VDR functions by regulating transcription in a ligand- (or Vit D-) dependent manner. In the body, Vit D and VDR together regulate the amount of calcium which is absorbed in the gut and ultimately deposited in bone. Thus, Vit D leads to an increase in available Ca 2+ .
In addition to its role in bone structure, calcium also regulates gene transcription. Calcium-activated transcription is mediated in part through cAMP response elements (CREs) located in the promoters of calcium-regulated genes. The CRE-binding protein, CREB, is a transcription factor with a well-established role in Ca 2+ -activated transcription. CREB is activated in a calcium-dependent manner through the Ca 2+ /CaM-dependent kinase IV (CaMK IV) and MAP-kinase pathways. Because Vit D regulates calcium levels, and calcium regulates transcription, we are interested in studying the potential interplays between Vit D/VDR- and Ca 2+ -regulated gene transcription.