Phone:
(859)323-5479
Fax:
(859) 323-6475
Nicholas J. Koszewski, PhD
Associate Professor of Medicine |
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University of Kentucky |
Phone: (859) 323-5049 |
Research/Clinical Interests: Our laboratory is interested in how vitamin D regulates the transcription of target genes. Specifically, we are looking at how this steroid hormone and its receptor are able to repress transcription of the parathyroid hormone, a key regulator of calcium homeostasis in the body. Thus far, we have been able to identify DNA sequences within the promoter regions of the rat and chicken parathyroid hormone genes that confers the repressive transcriptional effects of the hormone. Interestingly, a two base-pair change in the chicken DNA sequence is able to reverse the inherent repressive effect to yield an enhancer sequence with increased transcriptional activity. Our research is now focused on identifying additional co-factors that interact with the hormone-receptor-DNA complex to repress transcription of the parathyroid hormone gene. Selected Publications: Alimov, A. P., Langub, M.C., Malluche, H.H., Koszewski, N.J. Identification of an Sp1-like DNA element in the PTH promoter. Endocrinology 144:3138-3147, 2003. Rowan, A., Koszewski, N.J. Heterodimer requirement for negative gene regulation by vitamin D in variant OK cells. Steroids 68:307-314, 2003. Langub, M.C., Monier-Faugere, M.C., Wang, G., Williams, J.P., Koszewski, N.J., Malluche, H.H. Administration of PTH-(7-84) antagonizes the effects of PTH-(1-84) on bone in rats with moderate renal failure. Endocrinology 144:1135-1138, 2003. Malluche HH, Monier-Faugere, MC, Koszewski, NJ. Use and indication of vitamin D and vitamin D analogues in patients with renal bone disease. Nephrol Dial Transplant 17 Suppl 10:6-9, 2002. Malluche HH, Mawad H, Koszewski NJ. Update on vitamin D and its newer analogues: Actions and rationale for treatment in chronic renal failure. Kidney Int 62:367-74, 2002. |
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