The department of dermatology has a number of research lines embedded within the GROW research institute. Both clinical and molecular biological research is supported within the department, with a strong focus on the genetics of epithelial growth and (malignant) differentiation. The diversity in our research, sustained by a relatively small and nimble group, offers the opportunity to quickly move into promising new fields. In 2006, we published 36 papers in international peer-reviewed journals and 17 in national journals. This includes a number of high-impact papers.
Molecular genetics of inherited skin disease
Our department is a national referral center for the diagnosis and treatment of inherited skin disease and syndromal skin abnormalities. All molecular genetics research in the lab is patient-driven, an approach that is quite successful. Fourteen international papers covering this field of research were published in 2006, all of which appeared in high-impact specialist journals. Results include the identification of a new gene important for nail development, reported in a major genetic journal (Am J Hum Genet).
Functional analysis of lamin mutations causing lipodystrophy
Mutations in the LMNA/C gene that codes for nuclear lamina proteins cause a number of diseases characterized by an altered fat distribution. This includes progeroid syndromes and familial partial lipodystrophy. In an effort to understand the molecular mechanisms underlying the fat dystrophy in these diseases we have a PhD project in close collaboration with the department of molecular and cellular biology. This line has now generated exciting results and the first major paper concerning progeria has been published this year (Hum Mol Genet).
Gap junction biology
We have a strong track record in the identification of diseases caused by mutations in gap junction genes. We recently showed that a novel mutation in the GJA1 gene can cause oculo-dento-digital dysplasia with skin symptoms, an unexpected finding. Our discovery sheds new light on the function of GJA1 in the skin. Using mutant gap junction proteins fused to fluorescent reporter proteins, we are now examining the life cycle of gap junction proteins in animal cells. We also perform functional analysis of gap junctions in cell membranes in an international collaboration. We expect this research line to generate high-impact results.
Clinical oncology
Our department is a national referral center for the diagnosis and treatment of non-melanoma skin cancer and has played a major role in the development of Mohs' micrographic surgery for the treatment of basal cell carcinoma. Also alternatives for treatment of these cancers have been developed such as laser resurfacing. Our significant contribution in this field is reflected in the completion of two PhD theses (J. Ostertag, P. Quaedvlieg). Current research is shifting towards molecular oncology focusing on the elucidation of hereditary factors that predispose to developing basal cell carcinoma and other hair follicle tumors. A first publication in this field is on the cancer syndrome Birt-Hogg-Dubé, that is financially supported by the "profileringsfonds" to resolve the functional role of the involved protein.
Biological activities of retinoic acid metabolism blocking agents
Retinoic acid metabolism blocking agents (RAMBAs) are promising new compounds for the treatment of several inherited and acquired genetic disorders. In 2004 we completed a first clinical trial showing the efficacy of one such compound in psoriasis. The results of a second clinical trial with a RAMBA are ongoing. In collaboration with Barrier Therapeutics, Inc (Geel, Belgium), we have started experiments to explore other potential applications for RAMBAs and similar compounds in vitro.
Awards
Sadhanna Badeloe was elected "Clinician of the Year" in recognition of her contributions to medical training. The award is granted to clinicians whose teaching is judged to be outstanding by the medical students themselve
Grants
First stream:
azM, 4 years, AGIKO equivalent: molecular analysis of laminopathies.
PI: P.M. Steijlen & M.A.M. van Steensel
GROW, 1.5 years, 10.000 €: mismatch repair defects in multiple basal cell carcinoma.
PI: M.A.M. van Steensel
azM, 3 years, profileringsfonds, 150.000 €: Deregulation of HIF1 and mTOR as a cause of Birt-Hogg-Dubé syndrome.
PI: M.A.M. van Steensel, B. Wouters
Third stream:
Stichting de Drie Lichten, 1 year, 6.000 €: Regulation of gap junction gene expression.
PI: M.A.M. van Steensel
Fourth stream:
Barrier Therapeutics, 50.000 €/year: contract research in compound development
PI: P.M. Steijlen, M.A.M. van Steensel & M. van Geel
Research group
Prof. Dr. P.M. Steijlen, project leader
Prof. Dr. J.A. Frank
Dr. M. van Geel
Dr. A. Sommer
Dr. M.A.M. van Steensel
PhD students
Drs. S. Badeloe
Drs. N. Shahid
Drs. V.L.R.M. Verstraeten
Drs. E. de Zwart-Storm
Drs. D. Kuijpers
Drs. P. Quaedvlieg
Drs. R. Ceulen
Technicians
Ing. M. Kamps
Ing. R.S. Bladergroen
Drs. M.H. Lenders