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