Vitamin D Research
Vitamin D, Skin, and Bone Research Laboratory
Michael Holick, Phd, MD and his team of researchers continue to be leaders in the field of vitamin D, osteoporosis, metabolic bone disease, psoriasis and hair research.
Researchers successfully formulated the receptor agonist of parathyroid hormone related peptide, PTH (1-34), in a liposomal cream (Novasome A®). A pilot clinical trial was initiated to evaluate the safety and efficacy of topical administration of PTH (1-34) for the treatment of psoriasis. The pilot study’s results suggest that PTH (1-34) is both safe and effective for treating psoriasis, and offers a novel approach for treating this skin disease. Studies were initiated on the evaluation of PTH (1-34) and PTH (7-34) for preventing and treating chemotherapy-induced alopecia. C57 BL6 mice that received cyclophosphamide and were pretreated with PTH (7-34) were able to preserve their hair to a greater extent than the placebo-treated mice were. PTH (1-34) was effective in accelerating hair regrowth in mice that received cyclophosphamide.
We have initiated a program to evaluate the effect of vitamin D deficiency in advancing colon tumor growth in mice and the potential use of novel Gemini analogs to treat colan cancer.
Because the skin is an important source of vitamin D, a human skin equivalent and a liposomal model have been developed to mimic the photoproduction of vitamin D in human skin. Using these models systems, researchers demonstrated that during exposure to solar simulated-sunlight, a unique membrane-associated mechanism stabilizes the previtamin D3 in a cis,cis-conformation and results in its rapid conversion to vitamin D3. It has now been demonstrated that human skin also produces several photoproducts including tachysterol and lumisterol, which may have important biologic functions in the skin. Research is underway to further evaluate this.
Rahul Ray, Ph.D., Associate Professor of Medicine, continues to study structure-activity of binding proteins and nuclear transcriptional factors related to the vitamin D endocrine system: protein crystallography; molecular modeling; biochemical and mutational studies; gene regulation; molecular targeting of steroid hormone receptors for selective delivery of toxins to cancer cells; development of anti-cancer agents, small molecules and proteins; and identification and characterization of breast cancer-specific antigens.
The production of photoproducts of previtamin D3 and vitamin D3 was investigated. At least six photoproducts have been isolated and are being evaluated for their structure and biologic activity. To better understand how 1,25-dihydroxyvitamin D3 is produced in non-renal tissues such as the prostate, colon, and skin, the promoter region of the enzyme’s gene was cloned. It is being evaluated for its regulatory sequences. In addition an alternative spliced variant of the mRNA has been identified. Studies are underway to determine its function, gene regulation and use for gene therapy. Studies were conducted to determine the prevalence of vitamin D deficiency in cancer patients.
