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DermatologieForschungLaboratory of Epidermal Biology

Laboratory of Epidermal Biology 


  Copyright: S. Dubrac


Head: Associate Prof. Sandrine Dubrac

Research interest

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with a high yearly prevalence worldwide (affecting 2-26% of children and up to 18% of adults) that imposes a huge socioeconomic burden. The quality of life of AD patients is seriously impacted because of itching and scratching, which, in severe cases, can cause sleep deprivation, food limitation, pain, bleeding in children, and depression in adults. Importantly, AD is the initial step in the so-called ‘atopic march', where an average of 40% of children with AD goes on to develop asthma and/or allergic rhinitis later in life. AD is a complex disease whose full pathogenesis has not yet been elucidated. However, epidermal barrier impairment is considered the pathologic cornerstone of the disease.

Our research focuses on understanding cellular and molecular abnormalities leading to or worsening AD. We are exploring pathomechanisms involved in AD pathogenesis, including lipid and energy metabolism, oxidative stress and environmental triggers. A large network of collaborators based in the USA, Australia, and in several European countries participates to our ongoing projects, which connect the lab bench to the patient bed and may pave the way to the discovery of new therapeutic targets.

Our general question is: Which mechanisms promote the transition from healthy or normal appearing non-lesional atopic dermatitis skin to overt atopic dermatitis?

To answer this question, our strategy is the following:

Copyright: S. Dubrac


Our research has uncovered the role of Langerhans cell as well as metabolic perturbations in the pathogenies of atopic dermatitis.

Copyright: S. Dubrac


Sources of funding: MUI (2007-2009), FWF (2009-present), EU via the COST (2022-2026).

   

Patent: EP22187107.2: Antisense oligomers and methods for treating atopic dermatitis, psoriasis and other inflammatory conditions- Sandrine Dubrac-Coinventor


Publications

Selected publications

  1. Minzaghi D, Pavel P, Kremslehner C, Gruber F, Oberreiter S, Hagenbuchner J, Del Frari B, Blunder S, Gruber R, Dubrac S (2023). Excessive production of hydrogen peroxide in mitochondria contributes to atopic dermatitis. J Invest Dermatol. 143(10):1906-1918.e8.
  2. Holzknecht J, Dubrac S, Hedtrich S, Galgóczy L, Marx F (2022). Small, cationic antifungal proteins from filamentous fungi inhibit Candida albicans growth in 3D skin infection models. Microbiol Spectr 10(3):e0029922.
  3. Leman G, Pavel P, Hermann M, Crumrine D, Elias PM, Minzaghi D, Goudounèche D, Roshardt Prieto NM, Wanner A, Blunder S, Gruber R, Dubrac S (2022). Mitochondrial activity is up-regulated in nonlesional atopic dermatitis and amenable to therapeutic intervention. J Invest Dermatol 142(10):2623-2634.e12.
  4. Pavel P, Leman G, Hermann M, Ploner C, Eichmann TO, Minzaghi D, Radner FPW, Del Frari B, Gruber R, Dubrac S (2021): Peroxisomal fatty acid oxidation and glycolysis are triggered in lesional atopic dermatitis. JID Innovations 1(3):100033.
  5. Blunder S, Krimbacher T, Moosbrugger-Martinz V, Gruber R, Schmuth M, Dubrac S (2021): Keratinocyte-derived IL-1 β induces PPARG down-regulation and PPARD up-regulation in human reconstructed epidermis following barrier impairment. Exp Dermatol 30(9):1298-1308.
  6. Moosbrugger-Martinz V, Hackl H, Gruber R, Pilecky M, Knabl L, Orth-Höller D, Dubrac S (2021): Initial evidences of distinguishable bacterial and fungal dysbiosis in the skin of patients with Atopic Dermatitis or Netherton Syndrome. J Invest Dermatol 141(1):114-123.
  7. Moosbrugger-Martinz V, Gruber R, Ladstätter K, Bellutti M, Blunder S, Schmuth M, Dubrac S (2019): Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis. J Cell Mol Med 23(2):1288-1299.
  8. Blunder S, Kõks S, Kõks G, Reimann E, Hackl H, Gruber R, Moosbrugger-Martinz V, Schmuth M, Dubrac S (2018): Enhanced Expression of Genes Related to Xenobiotic Metabolism in the Skin of Patients with Atopic Dermatitis but Not with Ichthyosis Vulgaris. J Invest Dermatol 138(1):98-108.
  9. Elentner A, Schmuth M, Yannoutsos N, Eichmann TO, Gruber R, Radner FPW, Hermann M, Del Frari B, Dubrac S (2018): Epidermal Overexpression of Xenobiotic Receptor PXR Impairs the Epidermal Barrier and Triggers Th2 Immune Response. J Invest Dermatol 138(1):109-120.
  10. Blunder S, Rühl R, Moosbrugger-Martinz V, Krimmel C, Geisler A, Crumrine D, Elias P, Gruber R, Schmuth M, Dubrac S (2017): Alterations in epidermal eicosanoid metabolism contribute to inflammation and impaired late differentiation in FLG-mutated AD. J Invest Dermatol 137(3):706-715.
  11. Moosbrugger-Martinz V, Tripp CH, Gruber R, Clausen B, Finke D, Heufler C, Fiegl H, Schmuth M, Dubrac S (2016): Atopic dermatitis induces the expansion of thymus-derived regulatory T cells exhibiting a Th2-like phenotype. J Cell Mol Med  20(5): 930-8.
  12. Elentner E, Ortner D, Clausen B, Gonzalez FJ, Fernández Salguero PM, Schmuth M, Dubrac S (2015): Skin response to a carcinogen involves the xenobiotic receptor pregnane X receptor. Exp Dermatol 24(11): 835-40. 
  13. Dubrac S, Elentner A, Schoonjans K, Auwerx J, Schmuth M (2011): Lack of IL-2 in PPAR-alpha deficient mice triggers allergic contact dermatitis by affecting regulatory T cells; Eur J Immunol 41(7): 1980-1991.
  14. Dubrac S, Elentner A, Horejs-Hoeck J, Schmuth M (2010): Modulation of T-lymphocyte function by the Pregnane X Receptor (PXR); J Immunol 184(6): 2949-2957.
  15. Elentner A, Finke D, Schmuth M, Chappaz S, Ebner S, Malissen B, Kissenpfennig A, Romani N, Dubrac S (2009): Langerhans cells are critical in the development of atopic dermatitis-like inflammation and symptoms in mice; J Cell Mol Med  13(8B): 2658-2672.
  16. Dubrac S, Stoitzner P, Pirkebner D, Elentner A, Shoonjans K, Auwrex J, Saeland S, Hengster P, Fritsch P, Romani N, Schmuth M (2007): Peroxisome Proliferator-Activated Receptor-alpha activation inhibits Langerhans cell function; J Immunol 178(7): 4362-4372.

    Selected reviews

  17. Moosbrugger-Martinz V, Leprince C, Méchin MC, Simon M, Blunder S, Gruber R, Dubrac S (2022). Revisiting the roles of filaggrin in atopic dermatitis. IJMS 23(10): 5318.
  18. Pavel P, Elias PM, Dubrac S (2022). Atopic Dermatitis: The Fate of the Fat. IJMS 23(4):2121.
  19. Blunder S, Pavel P, Minzaghi D, Dubrac S (2021): PPARdelta in Affected Atopic Dermatitis and Psoriasis: A Possible Role in Metabolic Reprograming. IJMS 22(14):7354.
  20. van den Bogaard E, Ilic D, Dubrac S, Tomic-Canic M, Bouwstra J, Celli A, Mauro T (2021): Barrier Function of Mammalian Skin Gordon Research Conference, Waterville Valley, New Hampshire. Perspective and Consensus Opinion: Good Practices for Using Organotypic Skin and Epidermal Equivalents in Experimental Dermatology Research. J Invest Dermatol 141(1): 203-205.
  21. Minzaghi D, Pavel P, Dubrac S (2019): Xenobiotic Receptors and Their Mates in Atopic Dermatitis. IJMS 29;20(17). pii: E4234.
  22. Leman G, Moosbrugger-Martinz V, Blunder S, Pavel P, Dubrac S (2019): 3D-Organotypic Cultures to Unravel Molecular and Cellular Abnormalities in Atopic Dermatitis and Ichthyosis Vulgaris. Cells 22;8(5). pii: E489.
  23. Schmuth M, Moosbrugger-Martinz V, Blunder S, Dubrac S (2014): Role of PPAR, LXR, and PXR in epidermal homeostasis and inflammation. BBA 1841 (3): 463-473.
  24. Dubrac S, Schmuth M, Ebner S (2010): Atopic dermatitis: the role of Langerhans cells in disease pathogenesis. Immunol Cell Biol 88: 400-409.

Link to all publications:

https://pubmed.ncbi.nlm.nih.gov/?term=%28%28Dubrac+S%5BAuthor%5D%29+NOT+%28Sarah+Dubrac%5BAuthor%5D%29%29+NOT+%28Touati%5BAuthor%5D%29&sort=date

The Team

Associate Professor Sandrine Dubrac, Head of the Lab

Sandrine Dubrac is an Associate Professor in the Department of Dermatology, Venereology and Allergology, at the Medical University of Innsbruck. She earned a PhD degree from the University Paris Diderot - Orsay University (Paris XI) in Paris, France in 2001. After a postdoctoral fellowship in the Department of Metabolism at the University of California, San Francisco (UCSF), USA, she moved to the Medical University of Innsbruck for a second postdoctoral fellowship at the Department of Dermatology. There, she went on to establish her own laboratory to investigate atopic dermatitis. She earns several prizes and awards from the French Ministry of Foreign Affairs, The French Ministry of Science and Education, The French Society of Nutrition, the Singer-Polignac Foundation, Auspritz Prize, Unilever Prize, The International society of PPAR research, the Austrian Society of Dermatology (ÖGDV). Prof. Dubrac's research focuses on the interplay between epidermal barrier impairment and immune abnormalities in atopic dermatitis, with emphasis on lipid and xenobiotic metabolism in keratinocytes. Her laboratory aims to better understand the primary events involved in the pathogenesis of atopic dermatitis. Prof. Dubrac is currently member of the European Society for Dermatological Research (ESDR) board (2022-2027) and Chair of the EU-funded COST Action (CA21108) on skin engineering.

https://www.cost.eu/actions/CA21108/

https://netskinmodels-cost.com/


CA21108 - European Network for Skin Engineering and Modeling (NETSKINMODELS)

Over the past years, investigative and experimental dermatology has developed various approaches, ranging from utilisation of ex-vivo skin tissues to establishment of reconstructed in-vitro and in-silico skin models as tools in both basic and translational skin research. These models have the strong potential to increase the significance of scientific and clinical outcomes and to reduce animal experimentation. Nevertheless, current skin models lack sophistication and standardisation, thereby hampering their wider acceptance by the scientific community and regulatory bodies. This is partly caused by a lack of cross talk between relevant stakeholders — regulatory bodies, basic scientists, clinicians, and industry — whereby advances in new technologies have not delivered their full potential in this field.

In the proposed Action, interdisciplinary and intersectoral research and coordinated initiatives will drive the development and validation of standout sophisticated cell-based and computational skin models, including the development of artificial intelligence models for dermatological research. Furthermore, the Action has ambitions to develop ethical and sustainable reagents required for the elaboration of organotypic skin models, based on a strong partnership between network academia and industries. Harmonisation of scientific and technological knowledge and an enduring bottom-up dynamic in the field will be ensured by dissemination of leading-edge know-how among research intensive and research moderate European territories. Moreover, next-generation scientists will be trained for the long-term propagation and continued development of skin models. Action outcomes will turbocharge the field of skin models to meet rising scientific, clinical, economic, environmental and regulatory expectations, making Europe the epicentre of research in this field.

The COST Action includes 350 participants in 40 countries and 17 international companies.

Present and past students

Students who earned prizes and awards are in bold.


Stefan Blunder, MD, PhD

Deborah Minzaghi, Mag. Pharma, PhD / Ausgezeichnet - Medizinische Universität Innsbruck (i-med.ac.at)

Petra Pavel, Dr. Pharma, PhD

Géraldine Leman, PhD

Verena Moosbrugger-Martinz, MD, PhD

Huiting Zhu, MD

Master students: Romane Cadot, Philipp Boussard, Laura Hafferle

Bachelor students: Christoph Winkler (MD), Rebecca Gröbner, Özcan Sesli

MD Students: Andrea Wanner, Andreas Innerhofer, Anna-Lena Steinbrecher, Bettina Müller, Bianca Schaffenrath, Christine Krimmel, Cosimo Costanzia di Costigliole, Daniel Passini, Iris Grünen, Jakob Schnegg, Judith Gasl, Julia Grünwald, Julia Zimmermann, Katharina Ladstätter, Katharina Maurer, Lena Schnepf, Lisa Guggenburger, Mustafa al Jorani, Natalia Maria Roshardt Prieto, Nele Wichtmann, Nina Jocher, Rita Mahmuti, Sarah Maurer, Silvia Anlvidalfarei, Sofia Nischler, Sophie Ehrle, Sophie Oberreiter, Sorin Ungureanu, Thomas Krimbacher, Thomas Scheier, Thomas Thafoier, Victoria Weimann, Aaron Otto

Present and past BMA

Andreas Elentner

Katharina Scwhabenbauer

Daniela Spielmann

Yasmin Elfaran



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