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2004 PC Project Grant Award
Maurice van Steensel, M.D. University Hospital Maastricht The Netherlands Project Title: Gap junction regulation of keratin expression
Biography Maurice A. M. van Steensel received his M.D. from Catholic University Nijmegen in 1996. He was a research physician at the Department of Human Genetics and completed his residency at that hospital. Since January 2003, he has been a Resident/clinical scientist at the Department of Dermatology, University Hospital Maastricht (The Netherlands). He has received a number of grants and awards relating to genes, control of expression of genes, and gap junctions in skin disease.
Abstract At the end of this project which is expected to last about one year, we will have established patterns of keratin expression in organotypic skin culture in the context of gap junction gene mutations. Altered keratin expression may indicate that gap junctions regulate keratin expression. We will simultaneously explore (in a related project) the effect that the mutations have on the gap junctions themselves.
Our working hypothesis is that the KID/HID syndrome mutations lead to a gain-of-function (the gap junctions will be in a continuous "open" configuration) with increased intracellular calcium levels as a result. Keratinocyte proliferation with expression of the keratins associated with it will occur. The other mutations should have not this effect. Measurement of calcium levels will be performed in mutant keratinocytes. If increased, intracellular calcium may be the messenger that allows gap junctions to regulate differentiation.
Also, the effect of gap junction composition needs to be examined. It is possible that only gap junctions containing CJB2 or CJB6 will affect nail growth. In that case, a massive parallel screen for small molecules that block GJB2/6 containing gap junctions may prove useful. |
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