Role of gender in the interaction of the lungs with the environment

The lung is continuously exposed to the environment, and most lung diseases, including Chronic Obstructive Pulmonary Disease (COPD), pneumonia, bronchial asthma, and lung cancer, result from exposure to environment-dependent toxins or microorganisms.

The influence of biological sex on this interaction and the underlying mechanisms are scarcely investigated. The aim of this project is to examine the role of sex at the clinical-epidemiological and molecular levels using the use cases of COPD and pneumonia. Based on existing cohorts (COSYCONET; German COPD study, n=2800; PULMOHOM, n=850; IMAGINE, n=500), gender-specific differences in disease progression, prognosis, exposure, and cofactors will be explored. Extensive data on biomarkers and microbiome metagenomics allow a connection between clinical data and biological fundamentals. In the bioinformatic comparative analysis, bacterial species and their enzymatic and signal pathways that differ between male and female participants are identified.

Sex-specific differences between women and men in the interaction between environmental toxins or microorganisms are identified in isolated lung epithelial cells and immune cells. Single-cell characterization, metabolomics, microbiome metagenomics, and functional studies are employed. The OMICS data are integrated to explore the sex-specific mechanisms of interaction between human and bacterial cells.

The project's data will demonstrate how gender influences the risk and course of lung diseases.

Gruppenfoto von Jun.-Prof. Dr. Daniela Yildiz, Prof. Dr. Olga V. Kalinina und Prof. Dr. Dr. Robert Bals

Project lead

Jun.-Prof. Dr. Daniela Yildiz (née Dreymueller)

Saarland University
Preclinical Centre for Molecular Signalling (PZMS)
Experimental and clinical pharmacology and toxicology

daniela.yildiz(at)uks.eu
ORCID: 0000-0002-9702-8581

Curriculum Vitae

Univ-Prof. Dr. Olga V. Kalinina

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)
Saarland University
Faculty of Medicine
Centre for Bioinformatics

olga.kalinina(at)helmholtz-hips.de
ORCID: 0000-0002-9445-477X

Curriculum Vitae

Univ.-Prof. Dr. Dr. Robert Bals

Saarland University Hospital
Clinic for Internal Medicine V

robert.bals(at)uks.eu
ORCID: 0000-0002-1472-9535

Curriculum Vitae

 

Team

  • Prof. Christoph Beißwenger
  • Dr. Christian Herr
  • Guangyi Chen
  • Ahmad Aljohmani
  • Mariana Guedes

Important publications

  1. Lommatzsch M, Speer T, Herr C, Jorres RA, Watz H, Muller A, Welte T, Vogelmeier CF, Bals R, group Cs. IgE is associated with exacerbations and lung function decline in COPD. Respir Res. 2022;23(1):1. Epub 20220104.

  2. Ritzmann F, Chitirala P, Kruger N, Hoffmann M, Zuo W, Lammert F, Smola S, Tov N, Alagem N, Lepper PM, Pohlmann S, Beisswenger C, Herr C, Bals R, Group AA-i-C-S. Therapeutic Application of Alpha-1 Antitrypsin in COVID-19. Am J Respir Crit Care Med. 2021;204(2):224-7. Epub 2021/05/08.

  3. Sprott RF, Ritzmann F, Langer F, Yao Y, Herr C, Kohl Y, Tschernig T, Bals R, Beisswenger C. Flagellin shifts 3D bronchospheres towards mucus hyperproduction. Respir Res. 2020;21(1):222. Epub 2020/08/28.

  4. Becker A, Vella G, Galata V, Rentz K, Beisswenger C, Herr C, Walter J, Tierling S, Slevogt H, Keller A, Bals R. The composition of the pulmonary microbiota in sarcoidosis - an observational study. Respir Res. 2019;20(1):46. Epub 2019/03/02.

  5. Conrad C, Yildiz D, Cleary SJ, Margraf A, Cook L, Schlomann U, Panaretou B, Bowser JL, Karmouty-Quintana H, Li J, Berg NK, Martin SC, Aljohmani A, Moussavi-Harami SF, Wang KM, Tian JJ, Magnen M, Valet C, Qiu L, Singer JP, Eltzschig HK, CAPSyS Study Group, Bertrams W, Herold S, Suttorp N, Schmeck B, Ball ZT, Zarbock A, Looney MR, Bartsch JW. ADAM8 signaling drives neutrophil migration and ARDS severity. JCI Insight. 2022;7(3):e149870

  6. Aljohmani A, Opitz B, Bischoff M, Yildiz, D. Pseudomonas aeruginosa Triggered Exosomal Release of ADAM10 Mediates Proteolytic Cleavage in Trans. Int. J. Mol. Sci. 2022, 23, 1259

  7. Habib P*, Dreymueller D*, Rösing B, Botung H, Slowik A, Zendedel A, Habib S, Hoffmann S, Beyer C. Estrogen serum concentration affects blood immune cell composition and polarization in human females under controlled ovarian stimulation. J Steroid Biochem Mol Biol 2018; 178:340-347

  8. Srikakulam SK, Keller S, Dabbaghie F, Bals R, Kalinina OV (2023) MetaProFi: A protein-based Bloom filter for storing and querying sequence data for accurate identification of functionally relevant genetic variants, Bioinformatics, 39(3): btad101.

  9. Louadi Z, Yuan K, Gress A, Tsoy O, Kalinina OV, Baumbach J, Kacprowski T, List M (2020) DIGGER: Exploring the functional role of alternative splicing in protein interactions. Nucl Acids Res, 2020 49(D1): D309–D318.

  10. Gress A, Ramensky V, Kalinina OV (2017). Spatial distribution of disease-associated variants in three-dimensional structures of protein complexes. Oncogenesis, 6(9): e380.