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Lung Organoids and Disease Modeling

Ana Ivonne Vazquez-Armendariz, PhD

Ana Ivonne Vazquez-Armendariz is appointed as Junior Group Leader at the Institute for Lung Health (ILH), Justus-Liebig University Giessen (JLU), Germany, where she leads the research group “Lung organoids and disease modelling”. She is a committee member of the international graduate program Molecular Biology and Medicine of the Lung (MBML), member of the excellence cluster Cardio-Pulmonary Institute (CPI) and the German Center for Lung Research (DZL).

Ana Ivonne Vazquez-Armendariz was born in Monterrey, Mexico. She obtained her bachelor degree on Clinical Biochemistry with honors from the Autonomous University of Nuevo Leon in Mexico in 2009. After graduation, she was awarded with a scholarship by the Mexican National Council of Science and Technology (CONACYT) to pursue her postgraduate degree in Germany. Vazquez-Armendariz completed her master degree in Molecular Medicine at the University of Medicine Charité, Germany in 2012. Vazquez-Armendariz early research focused on Mycobacterial infections, including the study of the immune response of diabetic patients with tuberculosis and crosstalk between alveolar epithelial cells and alveolar macrophages during Mycobacterial Infection. In 2013, she moved to Giessen where she did her PhD and postdoctoral training at the JLU Giessen in the lab of Prof. Susanne Herold. During this period, her research work centered on the establishment and refinement of three-dimensional (3D) murine bronchioalveolar lung organoid cultures obtained from adult somatic stem cells for modeling of lung development and disease.

The Vazquez-Armendariz lab focuses on the use of 3D lung organoid systems from adult somatic stem cells and induced pluripotent stem cells (iPSCs) for modeling lung disease, particularly as a tool to characterize the molecular crosstalk between the epithelial-mesenchymal-myeloid unit during lung infection, injury and repair. The lab is interested in the elucidation of the cell-specific molecular signaling pathways involved in disease resolution, especially in the context of pathogen-induced lung injury.

Viral infections are a leading cause of substantial seasonal and pandemic morbidity and mortality worldwide. For instance, severe IAV infection spreads to the lower respiratory tract causing edema formation in the alveolar compartment leading to the development of pneumonia, acute respiratory distress syndrome (ARDS), and death due to respiratory failure. In order to regain homeostasis following IAV-induced injury, stem cell-mediated epithelial repair mechanisms are necessary. The term organoids refer to 3D structures derived from single stem cells that differentiate into organ-specific cells types that self-organize to form a structure resembling the cellular organization and functionality of the organ of origin. In this regard, 3D organoid culture systems have rapidly emerged as powerful tools to study stem cells potential and disease.

Figure 1: Overview of research topics addressed in Vazquez-Armendariz group

Our recently established a bronchoalveolar lung organoid (BALO) model is comprised of spatially organized bronchiolar and alveolar structures after co-culture of bronchioalveolar stem cells (BASCs) with defined subsets of lung-resident mesenchymal cells (rMC). Within these organoids, cells in the alveolar-like regions differentiate into mature AECII and AECI, whereas the airway-like regions contain basal, secretory and ciliated cells. In addition, distinct subsets of platelet-derived growth factor receptor-alpha (PDGFRα) high- and low expressing rMC, myofibroblasts and lipofibroblasts, are located within or in close proximity to alveolar-like structures. These mesenchymal cells are crucial components of the stem cell niche and fulfill defined tasks during epithelial cell regeneration after injury. In the context of injury, BALO epithelium infected with different strains of IAV supports viral replication and spread, and mounts an antiviral immune response. Additionally, microinjection of IAV into BALO airway-like structures recapitulates proximal-to-distal spread of the infection and causes substantial loss of AEC in the infected alveolar-like areas, thus, modeling this particular aspect of the in vivo situation of IAV pneumonia. Moreover, BALO can be supplemented with resident lung immune cells (e.g., alveolar macrophages), that engraft into the BALO and represent a further cellular compartment to study in the context of viral infection. Therefore, the professorship for “Lung organoids and disease modelling” aims to employ complex organoid models to model diseases that affect the bronchoalveolar compartment of the lung by focusing on the following aims:

  1. Development of multicellular, highly differentiated, branched human lung organoid systems that closely resemble the lung architecture.
  2. Visualization of tissue regeneration after organoid injury induced by viral infection or other insults at high resolution and over time by microscopic analysis.
  3. Determine the role of distinct cell types present within the alveolar niche during infection, injury and repair by employment of bronchioalveolar stem cells, endothelial cells, mesenchymal cells and/or leukocytes carrying gain- or loss-of-function mutations, or from reporter mice, to identify cell-specific functions of individual genes.
  4. Monitor cellular interactions happening during injury by cell microinjection of relevant cell types into lung organoids such as tumor cells, neutrophils, and inflammatory macrophages to determine how and when distinct supporting cells contribute to disease resolution.
  5. Combine organoid models with the latest technology such as two-photon light-sheet fluorescence microscopy, single-cell RNA-sequencing and genome editing tools to identify novel molecular cues and cellular interactions occurring during infection, injury and repair.

 

Contact

Ana Ivonne Vazquez-Armendariz, Ph.D.
Group leader for lung organoids and disease modelling
Tutour of the international graduate program Molecular Biology and Medicine of the Lung (MBML)
Institute for lung health (ILH)
Cardio-Pulmonary Institute (CPI)
Member of the German Center for Lung Research (DZL)

Universities of Giessen and Marburg Lung Center (UGMLC)
Justus-Leibig University Giessen
Aulweg 132
35392 Giessen

 

Tel: +49 (0) 641 99 36402 (office)
Tel: +49 (0) 641 99  36406 (lab)
Fax: +49 (0) 641 99 36406

Email:
Ana.I.Vazquez-Armendariz@innere.med.uni-giessen.de

Ten most important publications

  1. Vazquez-Armendariz AI, Seeger W, Herold S, El Agha E. “Protocol for the generation of bronchiolospheres”. Star Prot. In revision.
  2. Vazquez-Armendariz AI, Herold S. “From clones to buds and branches: The use of lung organoids to model branching morphogenesis ex vivo”. Front Cell Dev Biol. 2020. doi: 3389/fcell.2021.631579. IF: 5.203
  3. Vazquez-Armendariz AI, Heiner M, El Agha E, Salwig I, Hoek A, Hessler MC, Shalashova I, Shrestha A, Carraro G, Mengel JP, Günther A, Morty R, Vadasz I, Schwemmle M, Kummer, W, Hain T, Goesmann A, Bellusci S, Seeger W, Braun T, Herold S. “Multilineage murine stem cells generate complex organoids to model distal lung development and disease”. EMBO J. 2020 Oct 28; e103476. doi: 10.15252/embj.2019103476, 2020. IF: 9.968
  4. Moiseenko A, Vazquez-Armendariz AI, Kheirollahi V, Chu X, Tata A, Rivetti S, Günther S, Lebrigand K, Herold S, Braun T, Mari B, De Langhe S, Kwapiszewska G, Günther A,   Chen C, Seeger W, Tata RP, Zhang JS, Bellusci S, El Agha E. “Identification of a repair-supportive mesenchymal cell (RSMC) population during airway epithelial regeneration”. Cell Rep. 2020; 33(12):108549. IF: 8.109
  5. Jones MR, Lingampally A, Wu J, Sedighi J, Ahmadvand N, Wilhelm J, Vazquez-Armendariz AI, Herold S, Chen C, Zhang JS, Bellusci S, Chao CM. “Evidence for Overlapping and Distinct Biological Activities and Transcriptional Targets Triggered by Fibroblast Growth Factor Receptor 2b Signaling between Mid- and Early Pseudoglandular Stages of Mouse Lung Development”. Cells. 2020 May 21;9(5):1274. doi: 10.3390/cells9051274. IF: 4.329
  6. Kheirollahi V, Wasnick RM, Biasin V, Vazquez-Armendariz AI, Chu X, Moiseenko A, Weiss A, Wilhelm J, Zhang JS, Kwapiszewska G, Herold S, Schermuly RT, Mari B, Li X, Seeger W, Günther A, Bellusci S, El Agha E. “Metformin Induces Lipogenic Differentiation in Myofibroblasts to Reverse Lung Fibrosis”. Nat Commun. 2019;10(1):2987. IF: 12.121
  7. Salwig I, Spitznagel B, Vazquez-Armendariz AI, Khalooghi K, Guenther S, Herold S, Szibor M, Braun T. “Bronchioalveolar stem cells are a main source for regeneration of distal lung epithelia in vivo”. EMBO J. 2019 Jun 17;38(12):e102099. doi: 10.15252/embj.2019102099. Epub 2019 Apr 26. IF: 9.968
  8. Schmoldt C, Vazquez-Armendariz AI, Shalashova I, Selvakumar B, Bremer CM, Peteranderl C, Wasnick R, Witte B, Gattenlöhner S, Fink L, Vadász I, Morty RE, Pleschka S, Seeger W, Günther A, Herold S. “IRE1 Signaling As a Putative Therapeutic Target in Influenza Virus-induced Pneumonia”. Am J Respir Cell Mol Biol. 2019 Oct;61(4):537-540. doi: 10.1165/rcmb.2019-0123LE. IF: 5.373
  9. Shrestha A, Carraro G, Nottet N, Vazquez-Armendariz AI, Herold S, Cordero J, Singh I, Wilhelm J, Barreto G, Morty R, El Agha E, Mari B, Chen C, Zhang JS, Chao CM, Bellusci S. “A critical role for miR-142 in alveolar epithelial lineage formation in mouse lung development”. Cell Mol Life Sci. 2019 Jul;76(14):2817-2832. doi: 10.1007/s00018-019-03067-8. Epub 2019 Mar 18. IF:7.03
  10. Quantius J, Schmoldt C, Vazquez-Armendariz AI, Becker C, El Agha E, Wilhelm J, Morty R, Vadász I, Mayer K, Gattenloehner S, Fink L, Matrosovich M, Li X, Seeger W, Lohmeyer J, Bellusci S, Herold S. “Influenza Virus Infects Epithelial Stem/Progenitor Cells of the Distal Lung: Impact on Fgfr2b-Driven Epithelial Repair”. PLoS Pathog. 2016 Jun; 12(6): e1005544. IF:6.22

Funding

Group Members

Doctoral Students

Marie Hessler, Anna-Lena Ament

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