Marta Palomo Irigoyen
Anna Spiegel Center of Translational Research,
Medical University of Vienna
Inflammatory skin diseases
Help me to win the Young Researcher
Award 2023 from Promega.
Why should you vote for me!
Skin diseases are the most common health conditions affecting over 900 million people according to the World Health Organization. Among inflammatory skin diseases (ISDs) which are complex conditions with unknown aetiology, I am investigating the ISD with the largest burden: Atopic Dermatitis (AD). Despite major efforts to gain insight into the cellular and molecular mechanisms underlying AD, an effective treatment is currently lacking. Promega YRA will therefore push further the boundaries of our current knowledge in AD pathophysiology by providing knowledge on the cellular and molecular mechanism behind aberrant S100A8 and S100A9 alarmin expression, Staphylococcus aureus infection and microbial dysbiosis that are observed in AD. My main goal is to identify the key clinically targetable molecule involved in skin and beyond, for example the gut. Thus, these results may convince pharmaceutical companies to start new clinical trials targeting alarmins and opening new avenues for future therapies for ISDs and gastrointestinal tract disorders, such as Inflammatory Bowel Diseases (IBD). Promega YRA is invaluable to push my research/project forward with the ultimate goal of improving timely diagnosis and treatment of AD and IBD, which will have an economic impact by avoiding misdiagnosis and decreasing therapeutic costs. This research will also have a significant societal impact, since half of Europeans and Americans have skin pathologies while 20% of children and 10% of adults worldwide suffer from AD. In other words, 373 million ISD patients in EU and 775 million AD patients worldwide could benefit from this project’s findings. Importantly, my research may also have an impact in understanding other disorders associated with S. aureus infection, such as osteomyelitis.
Abstract
Beyond skin inflammation: cell-specific immune-modulatory functions of S100A8/A9 alarmins Authors: Marta Palomo-Irigoyen, Tim Hendrikx, Latifa Bakiri, Silvia Hayer, Johanna Schaffenrath, Philipp Starkl, Sylvia Knapp, Erwin F. Wagner Skin diseases are among the most common health conditions affecting over 900 million people. Inflammatory skin diseases (ISDs) comprise a series of complex pathologies with unknown aetiology, such as Atopic Dermatitis (AD), which accounts for the largest ISD burden. Despite major efforts gaining insights in the cellular and molecular mechanisms underlying AD, an effective treatment is currently lacking. AD is accompanied by skin microbiota dysbiosis characterized by Staphylococcus aureus (SA) colonization. Furthermore, S100A8 (A8), S100A9 (A9) and their heterocomplex Calprotectin (CP) mainly released by keratinocytes and neutrophils are deregulated in AD and can act as antimicrobial peptides.
However, the cell-specific A8/A9 contribution to SA infection and systemic inflammation associated with AD is still elusive. A genetically engineered mouse model (GEMM) of AD, based on constitutive epidermal loss of JunB (JunB∆ep), was crossed to S100A9(A) knockout (JunB∆epS100a9-/-) or epidermal A9-deficient mice (JunB∆epS100a9∆ep). JunB∆ep mice with A9 loss-of-function in neutrophils were established by bone marrow transplantation of mice with Mrp8-Cre mediated A9 deletion.
Global A9 inactivation in JunB∆ep mice ameliorated AD-like skin lesions, reduced SA colonization, neutrophil recruitment and decreased inflammatory mediators including S100A8 (A8), IL-17, IL-36β, G-CSF, Neutrophil elastase (NE) and Myeloperoxidase (MPO) in the skin. Furthermore, JunB∆epS100a9-/- mice developed aggravated systemic inflammation with prominent swollen digits with SA penetration, bone erosion and local A8 upregulation, as well as increased neutrophil recruitment, NE and MPO. In contrast, JunB∆epS100a9∆ep mice displayed worsened skin lesions with increased SA overgrowth and elevated A8/A9-positive neutrophil infiltrate in the skin. Importantly, A9-deficiency in neutrophils improved skin lesions with reduced A8 and A9 in the skin, whereas CP levels were elevated compared to control bone marrow chimeras. Ongoing experiments aim to identify cell-specific A8/A9 role in gut dysbiosis associated to ISDs with the ultimate goal to identify the critical targets for ISD and IBD prevention strategies.
In summary, here we identified epithelial- and immune cell-specific functions of A8/A9 that modulate AD-like disease with potential therapeutic relevance.
Describe the activity of your laboratory in a few lines:
Our multidisciplinary lab covers different research lines in cell biology, genetics, immunology and microbiology, including skin inflammation, cancer-associated cachexia, lung fibrosis, liver diseases, and bone disorders. The group is funded by an ERC Advanced Grant, an ITN/EU PhD network grant, as well as the Austrian Academy of Sciences and the Medical University of Vienna. Our studies employ animal models and patient-derived material to analyse gene function in important diseases, with the ultimate goal of identifying novel biomarkers and therapeutic targets (https://www.meduniwien.ac.at/hp/dermatologie/wissenschaft-forschung/genes-and-disease-group-erwin-wagner/)
My main project aims to explore cell-specific function of antimicrobial peptides and alarmins such as S100A8, S00A9 and calprotectin during organ cross-talk and host-pathogen interaction that occur in Atopic Dermatitis, the most common inflammatory skin disease with limited therapeutic options.
What are your other interests outside of science?
My main interest in addition to science is to continue exploring outside of the lab, I love scuba diving and snowboarding; but I also like to get to know people and learn from them. Moreover, painting, swimming and spending time with my dog are on my must-do list to relax.
Tell us something about your scientific background :
I obtained my PhD in Neurosciences at Severo Ochoa Excellence CIC BioGUNE research center and University of the Basque Country, in Spain, in 2020. Mentorship of Dr. A. Woodhoo, ERC Consolidator grant holder and general director Prof. Dr. J.M. Mato, promoted my special interest in tackling global challenges, that was reflected in 4 co-authorship publications during the PhD (+1 first author follow up paper in preparation), 2 book chapters and, cum laude as well as international mention of the thesis by the University of the Basque Country. I was mainly involved in studying gene regulatory networks in Schwann cells and Peripheral Nervous System disorders, where we discovered RNA Binding protein HuR (Human antigen R) as a master regulator of transcriptional networks required for malignant peripheral nerve sheath tumors (MPNSTs), published in J. Clin. Invest. This study provided a pharmacological target for MPNSTs which made significant advancements to the field. I am currently working as a Postdoctoral Fellow and project leader in Erwin Wagner’s lab, at Medical University of Vienna, Austria, thanks to the APART-MINT grant from the Austrian Academy of Sciences. During my postdoc I became more passionate about science than ever by tackling global challenges in skin biology, such as microbiota and inter-organ communication, using genetically engineered mouse models for inflammatory skin diseases. Furthermore, I truly encourage open science and networking to advance in research.
Can you describe yourself in 3 adjectives?
Positive, ambitious, perseverant
If you were a famous scientist, who would you be?
Irène Joliot-Curie because of her important contribution to science and her active involvement in women's rights, societal progress and peace movements.