Research Group KLOMP

Faculty of Medicine, University Medical Centre Utrecht, Dept. of Metabolic & Endocrine Diseases
Contact: Dr. Leo Klomp
E-mail: l.klomp@umcutrecht.nl
Website: http://www.metabole-ziekten.nl

General research focus: Liver membrane transporters in health and disease

We focus on cell biological characterization of inherited metabolic disorders: We have characterized the ATP8B1 and ABCB11 genes as the underlying genetic causes of hereditary cholestasis syndromes. Currently, we are working on the functional characterization of the proteins encoded by these genes in the context of the regulation of bile salt secretion.
We are interested in the mechanisms of liver copper homeostasis in relation to copper storage disorders. We aim to obtain a comprehensive understanding of the cellular proteins that are involved in the import, sequestration, intracellular distribution and excretion of copper, and the regulation of these processes. This involves, in part, work on the copper transporter ATP7B, which is mutated in patients with Wilson disease and the copper homeostasis protein COMMD1, which is mutated in Bedlington terriers affected with Copper Toxicosis.
A third research line encompasses the role of L-serine and D-serine biosynthesis in the development of the central nervous system. We characterized 3-phosphoglycerate dehydrogenase (PGDH) deficiency as a disorder of L-serine and D-serine biosynthesis, characterized by severe neurological dysfunction. Further work is currently aimed at understanding the metabolism of serine in the context of NMDA-receptor activation and more common neurologic diseases including epilepsy, hypoxic-ischemic injury and schizophrenia.

Techniques: general molecular cell biology, protein biochemistry, confocal fluorescence microscopy, histochemistry, enzyme assay's, molecular genetics, protein-protein interactions, cell sorting

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