Team Boukamp: UV-induced skin carcinogenesis and skin aging

Team leader:
Prof. Dr. rer. nat. Petra Boukamp

Postdoc:
Dr. Elizabeth Pavez Loriè

PhD students:
Katharina Janke

Master student:
Andrea Ximena Riscanevo Gonzalez

Research profile

The team of Petra Boukamp investigates the process of carcinogenesis and aging in one particular organ, the skin. To their help they use state of the art long term in vitro models that have been created by former members of this team. Before joining the IUF in 2015, the Boukamp group expedited research in skin biology and skin carcinogenesis at the German Cancer Research center in Heidelberg (DKFZ) for several decades.

One major interest of the team is to understand the underlying biological mechanisms, both genetically and environmentally driven, that cause disturbance in the skin, in particular the ones giving rise to cancer. With regard to genetics the group has done a lot of work on chromosomal alterations and their mode of development (UV-induced telomere shortening and induction of telomeric aggregates as initiators of genomic instability), as well as the role of specific mutations. A second major direction of the group is in the field of bioengineering with regards to their skin in vitro models. These models were subsequently optimized in the last 15 years. The first 3D organotypic cultures were developed in order to investigate the organization and regulation of human skin, in particular of the epidermis, and the human epidermal stem cell as a warrantor for life-long regeneration. The early models were based on de-epidermised dermis and hydrogels. However, because of biologically driven self-destruction of the models they only allowed for a rather limited life span. Now the group has developed a new generation of organotypic cultures (OTCs) based on scaffold- or cell-derived matrix, giving rise to authentic dermal equivalents, which make it possible to extend the life of the in vitro cultures for as long as 6 months. With these long-term cultures which are known for their reproducibility and in vivo similarities they are able to address questions concerning the identity of the epidermal stem cells during normal regeneration, wound healing and skin aging and similarly important, the studies of skin carcinogenesis with the help of the HaCaT in vitro skin carcinogenesis model. These studies are performed with the group’s OTC skin cancer model, which allows tumor cell-specific invasion through the basement membrane into the underlying stroma, a prerequisite for tumor progression. The next aim of the team is to further develop the skin in vitro model techniques to be used in not only basic biological and medical research, but also for questions related to environmental dermatology.

Projects

The KAUVIR project

For some time the group has performed research concerning the role of UV irradiation in skin carcinogenesis and skin aging. A first consortium project funded by the BMBF (The German Federal Ministry of Education and Research) specifically addressed the role of UVA. Using additional UVB or IRA demonstrated that radiation with UVA in combination with UVB or IRA caused a different “damage profile” than UVA alone. Therefore, the newly funded BMBF project KAUVIR (combination instead of addition: UV to IR radiation in skin cancer and skin aging) concentrates on the consequences of irradiation with a novel light source that combines UV, visible light (VIS), and IR, thus mimicking sun light to a large extent. These studies are essential in order to get a better understanding of the “damaging” effects of “sun light” and in consequence more relevant risk estimation and prevention. The team is also very interested to determine the consequences and regulation induced by this combinatorial radiation (KAUVIR) on the skin cells in OTCs, i.e. in the tissue context. An important aspect in this context is the influence of Cyclosporine A (CsA). This drug is frequently used as immunosuppressant for organ transplant patients. Unfortunately, however, immunosuppression is strongly associated with an increased risk of skin cancer (carcinomatous catastrophe). Therefore, it is of our interest to establish a molecular and mechanistic link between CsA treatment and UV radiation. In addition, UV-induced skin cancer is a cancer of old age and with the help of our new OTC-based aging model we aim to elucidate also the relationship of UV radiation and skin aging.

Prof. Petra Boukamp coordinates the KAUVIR project. Co-operation partners are Prof. Jean Krutmann from IUF, Dr. Rüdiger Greinert and Dr. Beate Volkmer from the Elbeklinik Buxtehude and Dr. Alexander Rapp from the University Darmstadt.

Inflammatory response studies of the skin

Inflammatory cells are supposed to contribute to skin diseases and skin cancer. Therefore, we will implement as a new research focus the complementation respectively development of OTCs with inflammatory cells in order to address their role in UV-dependent skin cancer and aging. This is an IUF trans-research field approach where we collaborate closely with Prof. Esser’s group.

Selected publications

Nöske K, Stark HJ, Nevaril L, Berning M, Langbein L, Goyal A, Diederichs S, Boukamp P: Mitotic diversity in homeostatic human interfollicular epidermis. Int J Mol Sci 17(2), 2016. doi: 10.3390/ijms17020167

Sobel K, Tham M, Stark HJ, Stammer H, Prätzel-Wunder S, Bickenbach JR, Boukamp P: Wnt-3a-activated human fibroblasts promote human keratinocyte proliferation and matrix destruction. Int J Cancer 136(12): 2786-2798, 2015. doi: 10.1002/ijc.29336

Berning M, Prätzel-Wunder S, Bickenbach JR, Boukamp P: Three-dimensional in vitro skin and skin cancer models based on human fibroblast-derived matrix. Tissue Eng Part C Methods 21(9): 958-970, 2015. doi: 10.1089/ten.TEC.2014.0698

Cooperations

IUF internal:
AG Krutmann
AG Esser

National:
Dr. Rüdiger Greinert and Dr. Beate Volkmer, Elbeklinik Buxtehude
Dr. Alexander Rapp, University Darmstadt
Prof. Cornelia Mauch, Dermatologie Köln
Prof. Hanno Glimm, DKFZ Heidelberg
Dr. Jörg Galle, IZBI Leipzig
Prof. Jürgen Becker, DKTK Essen

International:
Prof. Sabine Werner, ETH Zürich, Switzerland
Prof. Irene Leigh, School of Medicine, Dundee, UK
Prof. Pritinder Kaur, School of Biomedical Sciences, Bentley Campus, Australia