Priscilla Dannies, PhD
Research & Publications
Biography
Research Summary
A major unanswered question in endocrinology is how protein hormones are concentrated into secretory granules. We have developed a model system of rat pituitary tumor cells, GH4C1 cells, which have few secretory granules, but can be induced to accumulate many and to store prolactin. We have identified mutants of human prolactin and human growth hormones that can not be stored themselves, and that interfere with the storage or stability of wild-type hormones.
We are investigating why these mutants behave as they do by physical techniques in solution and biochemical methods in cells. Dominant-negative mutants for secretion of hormones have been found in people deficient in growth hormone, vasopressin and amylin. Understanding how mutants of prolactin and growth hormone interfere with synthesis and storage or normal hormones will lead to understanding the mechanisms of these deficiencies as well as answering a basic question in endocrinology.
Extensive Research Description
We are investigating why these mutants behave as they do by physical techniques in solution and biochemical methods in cells. Dominant-negative mutants for secretion of hormones have been found in people deficient in growth hormone, vasopressin and amylin. Understanding how mutants of prolactin and growth hormone interfere with synthesis and storage or normal hormones will lead to understanding the mechanisms of these eficiencies as well as answering a basic question in endocrinology.
Coauthors
Research Interests
Endocrinology; Pharmacology; Prolactin; Vasopressins
Selected Publications
- Aggregation and lack of secretion of most newly synthesized proinsulin in non-beta-cell lines.Zhu YL, Abdo A, Gesmonde JF, Zawalich KC, Zawalich W, Dannies PS. Aggregation and lack of secretion of most newly synthesized proinsulin in non-beta-cell lines. Endocrinology 2004, 145:3840-9.
- Is there structural specificity in the reversible protein aggregates that are stored in secretory granules?Keeler C, Hodsdon ME, Dannies PS. Is there structural specificity in the reversible protein aggregates that are stored in secretory granules? Journal Of Molecular Neuroscience : MN 2004, 22:43-9.
- The tertiary structure and backbone dynamics of human prolactin.Keeler C, Dannies PS, Hodsdon ME. The tertiary structure and backbone dynamics of human prolactin. Journal Of Molecular Biology 2003, 328:1105-21.
- New GH-1 gene mutations: expanding the spectrum of causes of isolated growth hormone deficiency.Mullis PE, Deladoëy J, Dannies PS. New GH-1 gene mutations: expanding the spectrum of causes of isolated growth hormone deficiency. Journal Of Pediatric Endocrinology & Metabolism : JPEM 2002, 15 Suppl 5:1301-10.
- Prolonged retention after aggregation into secretory granules of human R183H-growth hormone (GH), a mutant that causes autosomal dominant GH deficiency type II.Zhu YL, Conway-Campbell B, Waters MJ, Dannies PS. Prolonged retention after aggregation into secretory granules of human R183H-growth hormone (GH), a mutant that causes autosomal dominant GH deficiency type II. Endocrinology 2002, 143:4243-8.