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Birgitte Mønster Christensen

Group Leader

Birgitte Mønster Christensen
Associate Professor
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RESEARCH
Renal regulation of water and sodium metabolism is one of the most fundamental homeostatic functions in man and is essential for the function of most organs. Many life-threatening diseases are associated with significant disturbances in the ability of the kidney to regulate water and sodium balance. This includes a number of kidney, liver, lung and heart diseases. The final reabsorption of water and sodium takes place in the distal nephron and the collecting duct under tight control of the hormones vasopressin and aldosterone. The key proteins involved are the vasopressin-regulated water channel aquaporin-2 (AQP2) and the epithelial sodium channel (ENaC). Mutations or dysregulation of AQP2 is associated with nephrogenic diabetes insipidus (NDI), a kidney disease which is characterized by the inability of the kidney to concentrate urine in response to vasopressin. Lithium is a widely used drug for manic depressive patients, but a side effect of this treatment is development of NDI and hence a severe polyuria. Li-induced NDI is associated with downregulation of AQP2 and a remodeling of the collecting duct, but the exact mechanisms for these changes are not known. Part of our research is focused on understanding the mechanisms for the development of lithium-induced nephrogenic diabetes insipidus and in general the molecular mechanism for AQP2 regulation. ENaC is located in the apical plasma membrane of aldosterone-sensitive epithelia cells in the distal nephron and collecting duct as a heterotrimer composed of the three subunits. The channel plays a critical role in sodium and potassium balance, blood volume and blood pressure. We are interested in understanding which specific part of the distal nephron and collecting duct are important for sodium homeostasis and to identify and investigate aldosterone-specific targets in this part of the kidney.

RESEARCH INTERESTS
Renal Na+ transport: determine the phenotype of mice with kidney tubule-specific gene deletion of ENaC subunits in order to understand which tubule segments are essential for sodium homeostasis. Identify and investigate aldosterone-specific targets in the kidney distal nephron.

Water channels, aquaporins (AQPs): understanding the molecular mechanism for AQP2 regulation in physiological and pathophysiological conditions.

Abnormal water homeostasis: understanding the mechanisms for the development of lithium-induced nephrogenic diabetes insipidus.

METHODOLOGIES
Transgenic mice: generation and phenotypic characterization of mice with kidney-specific gene deletions, isolation and analysis of specific kidney cells expressing fluorescent proteins.

Animal disease models: generation and characterization of mouse and rat models with conditions of abnormal sodium and water handling by the kidney.

Laser scanning confocal microscopy and light microscopy: examination of the cellular and subcellular localization of proteins in sections of fixed tissues and cells.

Electron microscopy: examination of the subcellular distribution of proteins using immuno-gold labeling.

Cell and molecular biology: immunoblotting, immunocytochemistry, immunohistochemistry, RNA purification, PCR, genotyping.

Proteomics/transcriptome analysis: identification of intracellular signaling pathways involved in water and sodium homeostasis using mass spectrometry based analysis and RNA sequencing. 

COLLABORATORS

  • Edith Hummler and Bernard Rossier, University of Lausanne, Schweiz
  • Mark A Knepper and Jason Hoffert, National Institutes of Health, Bethesda, MD, USA
  • Peter Deen, Radboud University, Nijmegen, Netherlands
  • Steffen Madsen, Syddansk Universitet, DK

RESEARCH GROUP MEMBERS
Søren Brandt Poulsen, PhD student; Francesco Trepiccione, PhD student.

 

 

 

                                                          

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Revideret 03.08.2016