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PD Dr. Hans Christian Hennies

Principal Investigator, CECAD Cologne

PD Dr. Hans Christian Hennies
Principal Investigator, CECAD Cologne
Tel.  +49 221 478 96802
h.hennies[at]uni-koeln.de

Cologne Center for Genomics
Uniklinik Köln
Weyertal 115b
50931 Köln
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Hans Christian Hennies

The research group around PD Dr. Hans Christian Hennies investigates the molecular basis of genetic disorders. Many of these are rare monogenic diseases, but especially multifactorial disorders, such as alopecia areata and Dupuytren’s contracture, are common. Their goal is to identify the underlying pathomechanisms for these diseases and use them to define new targets for therapies as part of translational research.

Our research: The primary focus of Dr. Hennies and his team is on rare, monogenic diseases, in particular diseases of the skin, hair and connective tissue. They have turned their attention to two more common diseases as well: alopecia areata, hair loss in round patches, and Dupuytren’s disease, a contracture of the hand caused by fibromatosis that often occurs at advanced age. Identification of mutations that trigger the conditions is instrumental to decode the underlying pathomechanisms.

Our successes: The greatest advance in research into multifactorial diseases has been an understanding of how diverse genetic loci contribute to cellular mechanisms and affect gene expression in different cell types. One key breakthrough in the study of Dupuytren’s disease is new insight into the importance of Wnt signaling: six of nine known chromosomal loci associated with the disease contain genes involved in these pathways. Researchers have demonstrated that Wnt signaling not only exhibits changes at the protein level, but also variants at the DNA level have a direct influence on the Wnt gene. Furthermore, the group has identified mutations in various rare skin diseases, which have revealed the importance of cellular adhesion and lipid metabolism for epidermal integrity and skin barrier function.

Our goals: Dr. Hennies and his team of researchers aim to identify causal genetic variants in order to derive molecular targets for new medicines. The team is also working on the development of cellular models for the different disorders, which facilitate personalized approaches and systematic testing of new substances.

Our methods/techniques: In their research, Dr. Hennies and his team use high-throughput methods in genomics, including next generation sequencing and SNP genotyping. A variety of complex human cell models allows for investigation of fibroblasts, keratinocytes and melanocytes in organotypic cell structures.

Figures
Figure 1
Figure 2

Figure 1: Generation of epidermal keratinocytes by differentiation of induced pluripotent stem cells.
A) Pluripotent stem cells were obtained by reprogramming of fibroblasts as shown by typical morphology, activity of alkaline phosphatase, and staining signals for Oct4 and Tra1-81 (left to right). B) Differentiation of induced pluripotent stem cells to the ectodermal fate showed synthesis of epithelial marker keratin 18, epidermal marker keratin 14, and ectodermal gatekeeper p63. C) Primary (first row) and iPS-derived keratinocytes were positive for epithelial markers CD104 (first and second row) and keratins 18, 14, and 5 (third row) in FACS analysis.

Figure 2: Genome-wide study of genetic association in Dupuytren’s disease (Dolmans et al 2011). A) Clinical presentation. B) Manhattan plot of genome-wide P values showed single-nucleotide polymorphisms (SNPs) associated with Dupuytren’s disease. The orange line denotes significance threshold (P = 5 × 10-8).

EXTERNAL Cooperations
  • Prof. Dr. D. Furniss, Oxford, UK
  • Prof. Dr. D. Kelsell, London, UK
  • Prof. Dr. M. Schäfer-Korting, Berlin, DE
  • Prof. M. Schmuth, Innsbruck, AT
  • Prof. Dr. H. Traupe, Münster, DE
  • Prof. Dr. P. Werker, Groningen, NL
  • other cooperations via the ERA-Net project SkinDev