The candidate plans to become an independent, established investigator in pediatric bone and mineral metabolism in a setting where clinical exposure will foster scientific curiosity applicable to a laboratory setting. The research addresses certain observations in patients with metabolic bone disease regarding the relationship between vitamin D metabolism and phosphate transport. The experiments systematically evaluate mitochondrial metabolism in animal models of defective PO4 transport. Examination of mitochondrial PO4 content and transports, and monitoring of biochemical events during mitochondrial respiration will be performed using classical methods. 1AlphaOHlase activity will be determined in association with mitochondrial respiration and with alterations in extramitochondrial ionic milieu. Chronic regulation of 1AlphaOHlase activity will be investigated with respect to alterations in PO4 transport and intracellular ionic milieu. We seek a mechanism with shared pathogenetic elements to explain the observed associated defects in PO4 transport and vitamin D metabolism. Yale University is a major scientific center attached to the Yale-New Haven Hospital. The sponsor will be of invaluable assistance in carrying out the proposed projects in a major area of his interest, mitochondrial biochemistry. His expertise and direct oversight of the project will provide an incomparable environment for training.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR001749-04
Application #
3079228
Study Section
Special Emphasis Panel (ADDK)
Project Start
1987-01-01
Project End
1991-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Sullivan, W; Carpenter, T; Glorieux, F et al. (1992) A prospective trial of phosphate and 1,25-dihydroxyvitamin D3 therapy in symptomatic adults with X-linked hypophosphatemic rickets. J Clin Endocrinol Metab 75:879-85
Gundberg, C M; Clough, M E; Carpenter, T O (1992) Development and validation of a radioimmunoassay for mouse osteocalcin: paradoxical response in the Hyp mouse. Endocrinology 130:1909-15
Carpenter, T O; Mackowiak, S J; Troiano, N et al. (1992) Osteocalcin and its message: relationship to bone histology in magnesium-deprived rats. Am J Physiol 263:E107-14