Krutmann research group: environmentally-induced skin and lung aging
Head of research group:
Univ.-Prof. Dr. med. Jean Krutmann 
Phone: +49 (0)211-3389-225
Postdocs:
Dr. rer. nat. Marc Majora
Dr. rer. nat. Marius Pollet
PhD student:
Sabine Schneider
Master student:
Mbaboh Ngah Wanneh
Student assistance:
Jennifer Schindler
Technical assistance:
Maren Knechten, BTA
Judith Schulz, BTA
Ingo Uthe, BTA
Team Dr. Unfried:
Priv.-Doz. Dr. rer. nat. Klaus Unfried (senior researcher, head)
Dr. rer. nat. Tamara Hornstein
Dr. rer. nat. Tim Spannbrucker
Team Prof. Dr. Boukamp:
Prof. Dr. rer. nat. Petra Boukamp (senior scientist, head)
Dr. rer. nat. Elizabeth Pavez Loriè, postdoc
Katharina Janke, PhD student
Andrea Ximena Riscanevo Gonzalez, Master student
More information
Research profile
The Krutmann research group investigates the molecular mechanisms that underlie environmentally-induced skin aging and associated skin diseases. Insights obtained hereby are translated into the development of novel preventive strategies, if possible. Main topics of the last years are: (1) the discovery of the promoting effects of solar IRA radiation on skin aging and the development of corresponding skin protection products, (2) studies on the functional relevance of UV-induced mitochondrial mutagenesis in skin aging, (3) system biology investigations regarding UV-induced stroma aging of the skin, (4) and the discovery of the first curative therapeutic approach for the UV-sensitive progeroid syndrome Cockayne syndrome. Together with PD Dr. K. Unfried the development of an Ectoin-based medical product for the prevention of airborne particle (PM) induced lung aging was recently achieved. In IUF internal cooperation on epidemiological studies, an association between PM-exposure and skin aging was described for the first time. This finding is currently further investigated in a large Chinese cohort and moreover mechanistically investigated. In cooperation with the toxicological working groups, the role of the aryl hydrocarbon receptor in PM- and UV-induced skin aging and carcinogenesis is respectively analyzed. In cooperation with the immunological working groups the role of the innate immune system in extrinsic skin aging is being investigated.
Projects
The project "Gerontosys: Systems Biology of Stromal
Aging" was initially funded by the Federal Ministry of Education and
Research. Current activities are mainly covered by industry means. A
systems biology analysis of intrinsic and extrinsic aging processes in
the model of human skin fibroblasts is being conducted in a network of
researchers from Düsseldorf and Heidelberg. The IUF is hereby in charge
of the generation of a biobank of human skin fibroblasts that are
obtained from extrinsic and intrinsic aged skin of volunteers of
different age groups. Moreover, the IUF performs comparative
investigations on mitochondrial and epigenetic function parameters.
The
project „The role of the Cockayne syndrome B (CSB) protein in extrinsic
aging processes“ (initially funded within the SFB 728, currently by
iBRAIN und additional means from the industry) investigates the
mechanisms that are involved in premature aging processes triggered
through exogenic noxious agents in the progeroid syndrome Cockayne
syndrome which is mainly caused by mutations in the CSB gene. We were
able to show that the aggravation of the skin aging phenotype of
CSB-deficient mice and human fibroblasts upon UV radiation can be
ascribed to disturbances in autophagic processes. Together with the
Ventura research group, very similar findings in C. elegans were made.
Based on this, for the first time we identified a therapeutic approach
which was able to rescue the skin phenotype of the mouse model. Current
research aims to elucidate the molecular mechanisms that are responsible
for this curative effect. Besides an accelerated skin aging phenotype,
patients show neurodegenerative changes. As these are only mildly
pronounced in the mouse model, differentiated human neurospheres are
currently generated from human iPS cells derived from CS patients and
phenotypically and functionally characterized. This work is conducted in
close colaboration with the Fritsche research group.
The project
„KAUVIR: Combination instead of addition: UV and IR radiation in the
development of cancer and aging “ (funded by the Federal Ministry of
Education and Research; conducted together with the team Dr. Boukamp)
deals with the interaction between different wavelength ranges that are
part of the natural sunlight and lead to biological reactions in human
skin. The radiation spectrum of the sun contains UVA, UVB, visible light
(VIS) und infrared (IR) radiation that each has specific profiles
concerning their effects and cellular damage potential. We were able to
show that combinations of radiation e.g. UV and IR do not compulsorily
lead to an addition of the changes caused by the single spectrum but to
an unexpected third or even neutralizing reaction. Therefore, this
project investigates the combined action of UV and IR radiation
regarding their biological effects on the skin at different levels.
Using 2 dimensional and 3 dimensional organotypic cultures, the mouse
model as well as in vivo in human skin the corresponding effects of the
combined radiation compared to the single radiation is analyzed on
cellular, genetic and epigenetic levels. Moreover, together with the
research groups Haarmann-Stemmann, Esser and Fritsche investigations
concerning the role of the AhR in photocarcinogenesis, extrinsic (UV and
PM-triggered) skin aging, pathogenesis of inflammation reactions in the
skin are being conducted. This work is supported by a scholarship of
the Nagoya City University, Japan, as well as industry means.
The
project "Identification of cellular responses relevant for the safety
assessment of modern nanomaterials" (Head: Dr. Unfried) deals with the
development of test systems for the identification and assessment of
risks of these materials for humans. In the framework of the Leibniz PhD
project based on complementary expertise at the IUF and the “INM -
Leibniz-Institut für Neue Materialien” in Saarbrücken, mechanistic
basics to establish those test systems shall be developed. This project
is created as an integral part of the Alliance Nanosafety of the Leibniz
Association with research work at both institutes.
The project
"Identification of molecular mechanisms of carbon nanoparticle-induced
senescence and aging ex vivo and in vivo: Role of reactive oxygen
species" is a partial project of a jointly DFG individual application
that was obtained together with the Haendeler research group. Both
groups could show the induction of cellular senescence in lung
epithelial cells as well as endothelial cells in jointly preparatory
work (Büchner et al., 2013). The partial project, which is led by Dr.
Unfried, investigates the molecular mechanisms of the formation of
reactive oxygen species in primary human lung epithelial cells upon
contact with environmental relevant carbon particles. The relevance of
these events for the cellular senescence and the development of aging
phenotypes in the lung is validated in cell cultures as well as suitable
animal models.
Service
The Krutmann research group is together with Dr. S. Grether-Beck in charge of the IUF’s „Human in vivo studies“ (Heads: Prof. Dr. J. Krutmann, Dr. S. Grether-Beck).
Cooperations
IUF internal:
Esser research group
Fritsche research group
Haendeler research group
Schikowski junior research group
Schins research group
von Mikecz research group
Haarmann-Stemmann junior research group
Ventura liaison research group
Weighardt liaison research group
National:
Prof. Mark Berneburg, University Hospital Regensburg
Dr. Annette Kraegeloh, Leibniz Institute for New Materials (INM), Saarbrücken
und Leibniz Alliance Nanosafety
Dr. Harald Jungnickel, Federal Institute for risk assessment (BfR), Berlin
Dr. Ingrid Haußer-Siller, University Hospital Heidelberg
International:
Prof. Jean-Marc Egly, University of Strasbourg, France
Dr. Ivana Fenoglio, PhD, Dipartimento di Chimica, Università degli Studi di
Torino, Italy
Dr. Fernando Larcher, Centro de Investigaciones Energéticas, Medioambientales y
Tecnológicas (CIEMAT), Madrid, Spain
Dr. Sijia Wang, PICB, Shanghai, China
Selected publications
Krutmann J, Passeron T, Gilaberte Y, Granger C, Leone G, Narda M,
Schalka S, Trullas C, Masson P, Lim HW: Photoprotection of the future:
Challenges and opportunities. J Eur Acad Dermatol Venereol 34(3):
447-454, 2020. [pubmed] (open access)
Majora M, Sondenheimer K, Knechten M, Uthe I, Esser C, Schiavi A, Ventura
N, Krutmann J: HDAC inhibition improves autophagic and lysosomal function to
prevent loss of subcutaneous fat in a mouse model of Cockayne syndrome. Sci Transl Med 10(456): eaam7510, 2018. [pubmed]
Kroker M,
Sydlik U, Autengruber A, Cavelius C, Weighardt H, Kraegeloh A, Unfried K: Preventing
carbon nanoparticle-induced lung inflammation reduces antigen-specific
sensitization and subsequent allergic reactions in a mouse model. Part
Fibre Toxicol 12(1): 20, 2015. [pubmed]
(open access)
Sydlik U, Peuschel
H, Paunel-Görgülü A, Keymel S, Krämer U, Weissenberg A, Kroker M,
Seghrouchni S, Heiss C, Windolf J, Bilstein A, Kelm M, Krutmann J,
Unfried K: Recovery of neutrophil apoptosis by ectoine: a new strategy
against lung inflammation. Eur Respir J 41(2): 433-442, 2013. [pubmed]
Kamenisch
Y*, Fousteri M*, Knoch J, von Thaler AK, Fehrenbacher B, Dolle M,
Kuiper
R, Majora M, Schaller M, van Steeg H, Röcken M, Krutmann J*, Mullenders
LH*, Berneburg M: Proteins of nucleotide and base excision repair
pathways interact in mitochondria to protect from loss of subcutaneous
fat, a hallmark of aging. J Exp Med 207(2): 379-390, 2010.
(* equal contribution) [pubmed] (open access)
Fritsche E, Schäfer C, Bernsmann T, Calles C,
Wurm M, Hübenthal U, Cline J E, Schroeder P, Rannug A, Klotz L O, Fürst
P, Hanenberg H, Abel J, Krutmann J: Lightening up the UV response by
identification of the Arylhydrocarbon Receptor as a cytoplasmatic target
for ultraviolet B radiation. Proc Natl Acad Sci USA 104(21): 8851-8856,
2007. [pubmed] (open access)
Schwarz A, Ständer S, Berneburg M, Böhm M, Kulms D, van Steeg
H, Große-Heitmeyer K, Krutmann J, Schwarz T: Interleukin-12 suppresses
ultraviolet radiation-induced apoptosis by inducing DNA repair. Nature
Cell Biol 4(1): 26-31, 2002. [pubmed]
