Ligand Pharmaceuticals Inc. announced Monday that it hasreceived two grants totaling $435,000 over the next four yearsfrom the National Institutes of Diabetes and Digestive andKidney Diseases to study the role of vitamin D and itsintracellular receptor in human disease.

Ligand researchers J. Wesley Pike and Donald McDonnell -- incollaboration with Bert O'Malley of the Baylor College ofMedicine -- cloned the human vitamin D receptor while theywere at the Houston university in 1988, according to RobertStein, Ligand's vice president for research and preclinicaldevelopment.

Pike's group will use its grant to study the evolution, structure,function and biology of the vitamin D receptor and its gene,while McDonnell will investigate the receptor's structure andits functional domains.

Vitamin D affects bone growth and influences the immunesystem and the skin. It functions as a steroid hormone andplays an important role in regulating calcium metabolism. Butit also has profound effects on gene expression, according toStein. It can induce the differentiation of cells in culture, forinstance. "There's a lot of interest in the various activities ofvitamin D," Stein said.

The researchers hope to be able to separate vitamin D's effectson calcium handling and on differentiation through studying itsreceptor. And because "receptors make excellent targets forsmall molecules," it's possible to use this approach to treatdiseases such as psoriasis, Stein said. He added that there's alsoan interest in using vitamin D analogs to treat certain types ofcancer.

As well, the vitamin D receptor is part of a large family ofintracellular receptors. "The receptors for non-peptidehormones, including the glucocorticoids, sex hormones,retinoids and thyroid hormone, are closely relatedstructurally," Stein said.

Because they are similar, "what we learn (for vitamin Dreceptors) will work on other members of the receptorsuperfamily," Stein said.

Ligand of San Diego has major collaborative drug discovery anddevelopment programs with Pfizer Inc. in osteoporosis andGlaxo Inc. in cardiovascular disease. It also has a joint venturewith Allergan Inc. to study retinoids.

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