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Hire Dr. Hani N A.

Sweden

USD 100 /hr

Freelance Data Analyst & Bioinformatician | Expert in R & python and data visualization

Profile Summary

I recently completed my Postdoctoral Research in experimental medical sciences, with a specialization in lung bioengineering and regeneration. Through extensive experience developing advanced 3D culture models and utilizing cutting-edge methodologies—including light-sheet microscopy and bioinformatics—I have made significant contributions to the understanding of pulmonary diseases, particularly idiopathic pulmonary fibrosis. I have led research projects examining the role of co-transcriptional regulators in lung epithelium and the impact of the extracellular matrix on fibrotic processes. My findings have been presented at prestigious conferences and published in leading journals. Building on this foundation, I founded my own consulting company, offering specialized expertise in data analysis, bioinformatics, and web development. I am dedicated to leveraging my interdisciplinary skills to drive innovation and support ambitious research initiatives across the fields of life sciences and technology.

Subject Matter Expertise

• ☆ Biochemistry
• ☆ Immunoassay
• ☆ Biochemical Assays
• ☆ Enzyme Activity Assays
• ☆ Binding Assays
• ☆ Molecular Biology
• ☆ Genetics
• ☆ Microarrays
• ☆ Omics
• ☆ Transcriptomics
• ☆ Comparative Genomics
• ☆ Proteomics
• ☆ Genomics
• ☆ Epigenetics
• ☆ PCR
• ☆ Next Generation Sequencing (NGS)
• ☆ ATAC-Seq
• ☆ DNA Sequencing
• ☆ Gene Expression Analysis
• ☆ RNA Sequencing
• ☆ ChIP-Seq
• ☆ Cell Biology
• ☆ Cell-Based Assays
• ☆ Cytochemistry
• ☆ Cell Signaling Pathways
• ☆ Gene Regulation
• ☆ Stem Cell Research
• ☆ Histology
• ☆ Biotechnology & Bioengineering
• ☆ Bioprinting
• ☆ Microscopy
• ☆ Light Microscopy
• ☆ Electron Microscopy
• ☆ Fluorescence Microscopy
• ☆ Data Analysis
• ☆ Image Processing
• ☆ Data Processing
• ☆ Data Exploration
• ☆ Cluster Analysis
• ☆ Data Visualization
• ☆ Big Data Analytics
• ☆ Data Collection
• ☆ Data Management
• ☆ Data Manipulation
• ☆ Machine Learning
• ☆ Data Mining
• ☆ Statistics
• ☆ Comparative Analysis
• ☆ Regression Analysis
• ☆ Correlation Analysis
• ☆ Bioinformatics
• ☆ Gene & Protein Expression Analysis
• ☆ Cell Culture
• ☆ Primary Cells
• ☆ Cell Banking
• ☆ 3D Cell Culture
• ☆ Taxonomy/Classification
• ☆ Blotting
• ☆ Immunohistochemistry
• ☆ Tissue Engineering
• ☆ Python
• ☆ SQL
• ☆ Excel
• ☆ Markup Languages

Services

• Writing
• Research
• Consulting
• Data & AI
• Product Development

Writing Technical Writing, General Proofreading & Editing

Research Scientific and Technical Research

Consulting Operations Consulting, Scientific and Technical Consulting

Data & AI Statistical Analysis, Image Processing, Image Analysis, Data Visualization, Big Data Analytics, Data Mining, Data Cleaning, Data Processing

Product Development Prototyping

Work Experience

Founder

Scidetech AB

March 2025 - Present

PostDoc

Lund University

March 2023 - February 2025

PhD Candidate

Lund University

August 2018 - February 2023

Research Associate

Helmholtz Zentrum München

November 2015 - November 2017

Education

PhD in Biomedicine (Experimental Medical Sciences)

Lund University

August 2018 - February 2023

B.A. (Biochemistry Department)

Earlham College

August 2010 - May 2014

I.B.

United World College of the Adriatic

September 2008 - May 2010

Certifications

• Certification details not provided.

Publications

JOURNAL ARTICLE

Darcy Elizabeth Wagner, Hani N. Alsafadi, Nilay Mitash, Aurelien Justet, Qianjiang Hu, Ricardo Pineda, Claudia Staab-Weijnitz, Martina Korfei, Nika Gvazava, Kristin Wannemo, et al. (2025). Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models . Nature Communications.

Modeling fibrotic alveolar transitional cells with pluripotent stem cell-derived alveolar organoids @article{282c4a21294449ccb1470761344fab3a, title = "Modeling fibrotic alveolar transitional cells with pluripotent stem cell-derived alveolar organoids", abstract = "Repeated injury of the lung epithelium is proposed to be the main driver of idiopathic pulmonary fibrosis (IPF). However, available therapies do not specifically target the epithelium and human models of fibrotic epithelial damage with suitability for drug discovery are lacking. We developed a model of the aberrant epithelial reprogramming observed in IPF using alveolar organoids derived from human-induced pluripotent stem cells stimulated with a cocktail of pro-fibrotic and inflammatory cytokines. Deconvolution of RNA-seq data of alveolar organoids indicated that the fibrosis cocktail rapidly increased the proportion of transitional cell types including the KRT5-/KRT17+ aberrant basaloid phenotype recently identified in the lungs of IPF patients. We found that epithelial reprogramming and extracellular matrix (ECM) production persisted after removal of the fibrosis cocktail. We evaluated the effect of the two clinically approved compounds for IPF, nintedanib and pirfenidone, and found that they reduced the expression of ECM and pro-fibrotic mediators but did not completely reverse epithelial reprogramming. Thus, our system recapitulates key aspects of IPF and is a promising system for drug discovery.", author = "Victoria Ptasinski and Monkley, {Susan J.} and Karolina {\"O}st and Markus Tammia and Alsafadi, {Hani N.} and Catherine Overed-Sayer and Petra Hazon and Wagner, {Darcy E.} and Murray, {Lynne A.}", note = "Publisher Copyright: {\textcopyright} 2023 Ptasinski et al.", year = "2023", month = aug, day = "1", doi = "10.26508/lsa.202201853", language = "English", volume = "6", journal = "Life Science Alliance", issn = "2575-1077", publisher = "Rockefeller University Press", number = "8", } . Life Science Alliance.

Hani N Alsafadi, Victoria Ptasinski, Susan J Monkley, Karolina Öst, Markus Tammia, Catherine Overed-Sayer, Petra Hazon, Darcy E Wagner, Lynne A Murray (2023). Modeling fibrotic alveolar transitional cells with pluripotent stem cell-derived alveolar organoids . Life Science Alliance.

Hani N Alsafadi, Joanna Nowakowska, Anna Olechnowicz, Wojciech Langwiński, Oliwia Koteluk, Żaneta Lemańska, Kacper Jóźwiak, Kacper Kamiński, Wojciech Łosiewski, John Stegmayr, et al.(2023). Increased expression of ORMDL3 in allergic asthma . Journal of Asthma. 60. (3). p. 458--467. Taylor & Francis Group LLC Philadelphia

Hani N Alsafadi, John Stegmayr, Victoria Ptasinski, Iran Silva, Margareta Mittendorfer, Lynne A Murray, Darcy E Wagner(2022). Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations . Stem Cell Reports. 17. (12). p. 2718--2731. Cell Press

Wojciech Langwiński, Dawid Szczepankiewicz, Beata Narożna, John Stegmayr, Darcy Wagner, Hani Alsafadi, Sandra Lindstedt, Zuzanna Stachowiak, Joanna Nowakowska, Marek Skrzypski, et al.(2022). Allergic inflammation in lungs and nasal epithelium of rat model is regulated by tissue-specific miRNA expression . Molecular Immunology. 147. p. 115--125. Pergamon Press Ltd.

Highlights of the ers lung science conference and sleep and breathing conference 2021 and the new ecmc members @article{5a654307a888467092abfb5433a6c811, title = "Highlights of the ers lung science conference and sleep and breathing conference 2021 and the new ecmc members", author = "Goodwin, {Amanda T.} and Dilek Karadoğan and {De Santis}, {Martina M.} and Alsafadi, {Hani N.} and Ian Hawthorne and Matteo Bradicich and Matteo Siciliano and Duyar, {Sezgi {\c S}ahin} and Adriano Targa and Martina Meszaros and Michail Fanaridis and Thomas Gille and Keir, {Holly R.} and Moor, {Catharina C.} and Mona Lichtblau and Ubags, {Niki D.} and Joana Cruz", year = "2021", month = sep, day = "1", doi = "10.1183/20734735.0080-2021", language = "English", volume = "17", journal = "Breathe", issn = "1810-6838", publisher = "European Respiratory Society", number = "3", } . Breathe.

John Stegmayr, Hani N. Alsafadi, Wojciech Langwiński, Anna Niroomand, Sandra Lindstedt, Nicholas D. Leigh, Darcy E. Wagner(2021). Isolation of high-yield and -quality RNA from human precision-cut lung slices for RNA-sequencing and computational integration with larger patient cohorts . American Journal of Physiology-Lung Cellular and Molecular Physiology. 320. (2). p. L232--L240. American Physiological Society

Hani N Alsafadi, John Stegmayr, Wojciech Langwinski, Anna Niroomand, Sandra Lindstedt, Nicholas D Leigh, Darcy E Wagner(2021). Isolation of high yield and quality RNA from human precision-cut lung slices for RNA-sequencing and computational integration with larger patient cohorts . American Journal of Physiology: Lung Cellular and Molecular Physiology. 320. (2). p. L232--L240. American Physiological Society

Michael Gerckens, Kenji Schorpp, Francesco Pelizza, Melanie Wögrath, Kora Reichau, Huilong Ma, Armando Marco Dworsky, Arunima Sengupta, Mircea Gabriel Stoleriu, Katharina Heinzelmann, et al.(2021). Phenotypic drug screening in a human fibrosis model identified a novel class of antifibrotic therapeutics . Science Advances. 7. (52). p. 1--19. American Association for the Advancement of Science (AAAS)

Hani N Alsafadi, Martina M De Santis, Sinem Tas, Deniz A Bölükbas, Sujeethkumar Prithiviraj, Iran A Da Silva, Margareta Mittendorfer, Chiharu Ota, John Stegmayr, Fatima Daoud, et al.(2021). Extracellular-Matrix-Reinforced Bioinks for 3D Bioprinting Human Tissue . Advanced Materials. 33. (3). John Wiley & Sons Inc.

Inhibition of LTβR signalling activates WNT-induced regeneration in lung @article{5ad6043379f04b258bb8e356200ba240, title = "Inhibition of LTβR signalling activates WNT-induced regeneration in lung", abstract = "Lymphotoxin β-receptor (LTβR) signalling promotes lymphoid neogenesis and the development of tertiary lymphoid structures1,2, which are associated with severe chronic inflammatory diseases that span several organ systems3-6. How LTβR signalling drives chronic tissue damage particularly in the lung, the mechanism(s) that regulate this process, and whether LTβR blockade might be of therapeutic value have remained unclear. Here we demonstrate increased expression of LTβR ligands in adaptive and innate immune cells, enhanced non-canonical NF-κB signalling, and enriched LTβR target gene expression in lung epithelial cells from patients with smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke. Therapeutic inhibition of LTβR signalling in young and aged mice disrupted smoking-related inducible bronchus-associated lymphoid tissue, induced regeneration of lung tissue, and reverted airway fibrosis and systemic muscle wasting. Mechanistically, blockade of LTβR signalling dampened epithelial non-canonical activation of NF-κB, reduced TGFβ signalling in airways, and induced regeneration by preventing epithelial cell death and activating WNT/β-catenin signalling in alveolar epithelial progenitor cells. These findings suggest that inhibition of LTβR signalling represents a viable therapeutic option that combines prevention of tertiary lymphoid structures1 and inhibition of apoptosis with tissue-regenerative strategies.", author = "Conlon, {Thomas M} and Gerrit John-Schuster and Danijela Heide and Dominik Pfister and Mareike Lehmann and Yan Hu and Zeynep Ert{\"u}z and Lopez, {Martin A} and Meshal Ansari and Maximilian Strunz and Christoph Mayr and Chiara Ciminieri and Rita Costa and Kohlhepp, {Marlene Sophia} and Adrien Guillot and Gizem G{\"u}nes and Aicha Jeridi and Funk, {Maja C} and Giorgi Beroshvili and Sandra Prokosch and Jenny Hetzer and Verleden, {Stijn E} and Hani Alsafadi and Michael Lindner and Gerald Burgstaller and Lore Becker and Martin Irmler and Michael Dudek and Jakob Janzen and Eric Goffin and Reinoud Gosens and Percy Knolle and Bernard Pirotte and Tobias Stoeger and Johannes Beckers and Darcy Wagner and Indrabahadur Singh and Theis, {Fabian J} and {de Angelis}, {Martin Hrab{\'e}} and Tracy O'Connor and Frank Tacke and Michael Boutros and Emmanuel Dejardin and Oliver Eickelberg and Schiller, {Herbert B} and Melanie K{\"o}nigshoff and Mathias Heikenwalder and Yildirim, {Ali {\"O}nder}", year = "2020", month = dec, day = "3", doi = "10.1038/s41586-020-2882-8", language = "English", volume = "588", pages = "151--156", journal = "Nature", issn = "0028-0836", publisher = "Nature Publishing Group", number = "7836", } . Nature.

Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Disease 2019 @article{1411d21413114cc8a99e34638dad98d8, title = "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Disease 2019", abstract = "A workshop entitled {"}Stem Cells, Cell Therapies and Bioengineering in Lung Biology and Diseases{"} was hosted by the University of Vermont Larner College of Medicine in collaboration with the National Heart, Lung and Blood Institute, the Alpha-1 Foundation, the Cystic Fibrosis Foundation, the International Society for Cell and Gene Therapy and the Pulmonary Fibrosis Foundation. The event was held from July 15 to 18, 2019 at the University of Vermont, Burlington, Vermont. The objectives of the conference were to review and discuss the current status of the following active areas of research: 1) technological advancements in the analysis and visualisation of lung stem and progenitor cells; 2) evaluation of lung stem and progenitor cells in the context of their interactions with the niche; 3) progress toward the application and delivery of stem and progenitor cells for the treatment of lung diseases such as cystic fibrosis; 4) progress in induced pluripotent stem cell models and application for disease modelling; and 5) the emerging roles of cell therapy and extracellular vesicles in immunomodulation of the lung. This selection of topics represents some of the most dynamic research areas in which incredible progress continues to be made. The workshop also included active discussion on the regulation and commercialisation of regenerative medicine products and concluded with an open discussion to set priorities and recommendations for future research directions in basic and translation lung biology.", author = "Wagner, {Darcy E} and Laertis Ikonomou and Gilpin, {Sarah E} and Magin, {Chelsea M} and Fernanda Cruz and Allison Greaney and Mattias Magnusson and Ya-Wen Chen and Brian Davis and Kim Vanuytsel and {Rolandsson Enes}, Sara and Anna Krasnodembskaya and Mareike Lehmann and Gunilla Westergren-Thorsson and John Stegmayr and Alsafadi, {Hani N} and Hoffman, {Evan T} and Weiss, {Daniel J} and Ryan, {Amy L}", note = "Copyright {\textcopyright}ERS 2020.", year = "2020", month = oct, doi = "10.1183/23120541.00123-2020", language = "English", volume = "6", journal = "ERJ Open Research", issn = "2312-0541", publisher = "European Respiratory Society", number = "4", } . ERJ Open Research.

Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery @article{8c023ea68b0146b38f7f2474c606252c, title = "Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery", abstract = "Chronic lung diseases (CLDs), such as chronic obstructive pulmonary disease, interstitial lung disease, and lung cancer, are among the leading causes of morbidity globally and impose major health and financial burdens on patients and society. Effective treatments are scarce, and relevant human model systems to effectively study CLD pathomechanisms and thus discover and validate potential new targets and therapies are needed. Precision-cut lung slices (PCLS) from healthy and diseased human tissue represent one promising tool that can closely recapitulate the complexity of the lung's native environment, and recently, improved methodologies and accessibility to human tissue have led to an increased use of PCLS in CLD research. Here, we discuss approaches that use human PCLS to advance our understanding of CLD development, as well as drug discovery and validation for CLDs. PCLS enable investigators to study complex interactions among different cell types and the extracellular matrix in the native three-dimensional architecture of the lung. PCLS further allow for high-resolution (live) imaging of cellular functions in several dimensions. Importantly, PCLS can be derived from diseased lung tissue upon lung surgery or transplantation, thus allowing the study of CLDs in living human tissue. Moreover, CLDs can be modeled in PCLS derived from normal lung tissue to mimic the onset and progression of CLDs, complementing studies in end-stage diseased tissue. Altogether, PCLS are emerging as a remarkable tool to further bridge the gap between target identification and translation into clinical studies, and thus open novel avenues for future precision medicine approaches.", keywords = "drug discovery, ex vivo lung disease, PCLS, translation", author = "Alsafadi, {Hani N} and Uhl, {Franziska E.} and Pineda, {Ricardo H.} and Bailey, {Kolene E.} and Mauricio Rojas and Wagner, {Darcy E} and Melanie K{\"o}nigshoff", year = "2020", month = jun, day = "1", doi = "10.1165/rcmb.2019-0276TR", language = "English", volume = "62", pages = "681--691", journal = "American Journal of Respiratory Cell and Molecular Biology", issn = "1044-1549", publisher = "American Thoracic Society", number = "6", } . American Journal of Respiratory Cell and Molecular Biology.

Hani N. Alsafadi, Franziska E. Uhl, Ricardo H. Pineda, Kolene E. Bailey, Mauricio Rojas, Darcy E. Wagner, Melanie Königshoff(2020). Applications and Approaches for Three-Dimensional Precision-Cut Lung Slices. Disease Modeling and Drug Discovery . American Journal of Respiratory Cell and Molecular Biology. 62. (6). p. 681--691. American Thoracic Society

Generation of Human 3D Lung Tissue Cultures (3D-LTCs) for Disease Modeling @article{0330851a625b4591ab3b8c43280c3e22, title = "Generation of Human 3D Lung Tissue Cultures (3D-LTCs) for Disease Modeling", abstract = "Translation of novel discoveries to human disease is limited by the availability of human tissue-based models of disease. Precision-cut lung slices (PCLS) used as 3D lung tissue cultures (3D-LTCs) represent an elegant and biologically highly relevant 3D cell culture model, which highly resemble in situ tissue due to their complexity, biomechanics and molecular composition. Tissue slicing is widely applied in various animal models. 3D-LTCs derived from human PCLS can be used to analyze responses to novel drugs, which might further help to better understand the mechanisms and functional effects of drugs in human tissue. The preparation of PCLS from surgically resected lung tissue samples of patients, who experienced lung lobectomy, increases the accessibility of diseased and peritumoral tissue. Here, we describe a detailed protocol for the generation of human PCLS from surgically resected soft-elastic patient lung tissue. Agarose was introduced into the bronchoalveolar space of the resectates, thus preserving lung structure and increasing the tissue's stiffness, which is crucial for subsequent slicing. 500 µm thick slices were prepared from the tissue block with a vibratome. Biopsy punches taken from PCLS ensure comparable tissue sample sizes and further increase the amount of tissue samples. The generated lung tissue cultures can be applied in a variety of studies in human lung biology, including the pathophysiology and mechanisms of different diseases, such as fibrotic processes at its best at (sub-)cellular levels. The highest benefit of the 3D-LTC ex vivo model is its close representation of the in situ human lung in respect of 3D tissue architecture, cell type diversity and lung anatomy as well as the potential for assessment of tissue from individual patients, which is relevant to further develop novel strategies for precision medicine.", author = "Michael Gerckens and Alsafadi, {Hani N} and Wagner, {Darcy E} and Michael Lindner and Gerald Burgstaller and Melanie K{\"o}nigshoff", year = "2019", month = feb, day = "12", doi = "10.3791/58437", language = "English", journal = "Journal of visualized experiments : JoVE", issn = "1940-087X", publisher = "MyJoVE Corporation", number = "144", } . Journal of visualized experiments : JoVE.

Deniz A. Bölükbas, Martina M. De Santis, Hani N. Alsafadi, Ali Doryab, Darcy E. Wagner(2019). The Preparation of Decellularized Mouse Lung Matrix Scaffolds for Analysis of Lung Regenerative Cell Potential . Methods in molecular biology (Clifton, N.J.). 1940. p. 275--295. Springer

Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology 06 Biological Sciences 0601 Biochemistry and Cell Biology @article{10e39add05064bfab159c71057f8277c, title = "Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology 06 Biological Sciences 0601 Biochemistry and Cell Biology", abstract = "Background: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Repetitive injury and reprogramming of the lung epithelium are thought to be critical drivers of disease progression, contributing to fibroblast activation, extracellular matrix remodeling, and subsequently loss of lung architecture and function. To date, Pirfenidone and Nintedanib are the only approved drugs known to decelerate disease progression, however, if and how these drugs affect lung epithelial cell function, remains largely unexplored. Methods: We treated murine and human 3D ex vivo lung tissue cultures (3D-LTCs; generated from precision cut lung slices (PCLS)) as well as primary murine alveolar epithelial type II (pmATII) cells with Pirfenidone or Nintedanib. Murine 3D-LTCs or pmATII cells were derived from the bleomycin model of fibrosis. Early fibrotic changes were induced in human 3D-LTCs by a mixture of profibrotic factors. Epithelial and mesenchymal cell function was determined by qPCR, Western blotting, Immunofluorescent staining, and ELISA. Results: Low μM concentrations of Nintedanib (1 μM) and mM concentrations of Pirfenidone (2.5 mM) reduced fibrotic gene expression including Collagen 1a1 and Fibronectin in murine and human 3D-LTCs as well as pmATII cells. Notably, Nintedanib stabilized expression of distal lung epithelial cell markers, especially Surfactant Protein C in pmATII cells as well as in murine and human 3D-LTCs. Conclusions: Pirfenidone and Nintedanib exhibit distinct effects on murine and human epithelial cells, which might contribute to their anti-fibrotic action. Human 3D-LTCs represent a valuable tool to assess anti-fibrotic mechanisms of potential drugs for the treatment of IPF patients.", keywords = "ATII, Epithelial cells, ex vivo, IPF, Lung disease, Nintedanib, PCLS, Pirfenidone", author = "Mareike Lehmann and Lara Buhl and Alsafadi, {Hani N.} and Stephan Klee and Sarah Hermann and Kathrin Mutze and Chiharu Ota and Michael Lindner and J{\"u}rgen Behr and Anne Hilgendorff and Wagner, {Darcy E.} and Melanie K{\"o}nigshoff", year = "2018", month = sep, day = "15", doi = "10.1186/s12931-018-0876-y", language = "English", volume = "19", journal = "Respiratory Research", issn = "1465-9921", publisher = "BioMed Central (BMC)", number = "1", } . Respiratory Research.

Mareike Lehmann, Lara Buhl, Hani N. Alsafadi, Stephan Klee, Sarah Hermann, Kathrin Mutze, Chiharu Ota, Michael Lindner, Jürgen Behr, Anne Hilgendorff, et al.(2018). Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis . Respiratory Research. 19. (1). Springer Nature America, Inc

Chiharu Ota, John-Poul Ng-Blichfeldt, Martina Korfei, Hani N. Alsafadi, Mareike Lehmann, Wioletta Skronska-Wasek, Martina M. De Santis, Andreas Guenther, Darcy E. Wagner, Melanie Königshoff (2018). Dynamic expression of HOPX in alveolar epithelial cells reflects injury and repair during the progression of pulmonary fibrosis . Scientific Reports.

Dynamic expression of HOPX in alveolar epithelial cells reflects injury and repair during the progression of pulmonary fibrosis @article{62e5323cf7434ec591a030670f53dc00, title = "Dynamic expression of HOPX in alveolar epithelial cells reflects injury and repair during the progression of pulmonary fibrosis", abstract = "Mechanisms of injury and repair in alveolar epithelial cells (AECs) are critically involved in the progression of various lung diseases including idiopathic pulmonary fibrosis (IPF). Homeobox only protein x (HOPX) contributes to the formation of distal lung during development. In adult lung, alveolar epithelial type (AT) I cells express HOPX and lineage-labeled Hopx+ cells give rise to both ATI and ATII cells after pneumonectomy. However, the cell function of HOPX-expressing cells in adult fibrotic lung diseases has not been investigated. In this study, we have established a flow cytometry-based method to evaluate HOPX-expressing cells in the lung. HOPX expression in cultured ATII cells increased over culture time, which was accompanied by a decrease of proSP-C, an ATII marker. Moreover, HOPX expression was increased in AECs from bleomycin-instilled mouse lungs in vivo. Small interfering RNA-based knockdown of Hopx resulted in suppressing ATII-ATI trans-differentiation and activating cellular proliferation in vitro. In IPF lungs, HOPX expression was decreased in whole lungs and significantly correlated to a decline in lung function and progression of IPF. In conclusion, HOPX is upregulated during early alveolar injury and repair process in the lung. Decreased HOPX expression might contribute to failed regenerative processes in end-stage IPF lungs.", author = "Chiharu Ota and John-Poul Ng-Blichfeldt and Martina Korfei and Alsafadi, {Hani N.} and Mareike Lehmann and Wioletta Skronska-Wasek and {De Santis}, {Martina M.} and Andreas Guenther and Darcy Wagner and Melanie K{\"o}nigshoff", year = "2018", month = aug, day = "28", doi = "10.1038/s41598-018-31214-x", language = "English", volume = "8", journal = "Scientific Reports", issn = "2045-2322", publisher = "Nature Publishing Group", } . Scientific Reports.

Early Career Members at the ERS Lung Science Conference: cell-matrix interactions in lung disease and regeneration: Early career forum @article{c4310e20b8884789a007e41d03545b59, title = "Early Career Members at the ERS Lung Science Conference: cell-matrix interactions in lung disease and regeneration: Early career forum", abstract = "The 16th ERS Lung Science Conference (LSC) took place on March 8–11, 2018, in Estoril, Portugal, with around 200 delegates from all over the world. This year{\textquoteright}s topic was “Cell-matrix interactions in lung disease and regeneration” and involved excellent presentations by leading experts in the field covering everything from exploratory studies on how the matrix functions, matrix remodelling and biomarkers in disease, to more technical knowledge described in the field of lung bioengineering. As in previous years, the Saturday afternoon was reserved for a programme dedicated to early career delegates, which this year focussed on “Maximising your publication output”. In this article, we summarise the Early Career Member highlights of this year{\textquoteright}s LSC.", author = "Isaac Almendros and Alsafadi, {Hani N.} and Deniz B{\"o}l{\"u}kbas and Collins, {Jennifer JP} and Paula Duch and Garrido-Martin, {Eva M} and Nicholas Kahn and Theodoros Karampitsakos and {Mahmutovic Persson}, Irma and Argyrios Tzouvelekis and Franziska Uhl and Sabine Bartel", year = "2018", month = jun, doi = "10.1183/20734735.016818", language = "English", volume = "14", pages = "e78--e83", journal = "Breathe", issn = "1810-6838", publisher = "European Respiratory Society", number = "2", } . Breathe.

Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo @article{b93c7193ef194ef5ba08895df42f2d5e, title = "Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo", abstract = "Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with poor prognosis and limited therapeutic options. The incidence of IPF increases with age, and ageing-related mechanisms such as cellular senescence have been proposed as pathogenic drivers. The lung alveolar epithelium represents a major site of tissue injury in IPF and senescence of this cell population is probably detrimental to lung repair. However, the potential pathomechanisms of alveolar epithelial cell senescence and the impact of senolytic drugs on senescent lung cells and fibrosis remain unknown. Here we demonstrate that lung epithelial cells exhibit increased P16 and P21 expression as well as senescence-associated β-galactosidase activity in experimental and human lung fibrosis tissue and primary cells.Primary fibrotic mouse alveolar epithelial type (AT)II cells secreted increased amounts of senescence-associated secretory phenotype (SASP) factors in vitro, as analysed using quantitative PCR, mass spectrometry and ELISA. Importantly, pharmacological clearance of senescent cells by induction of apoptosis in fibrotic ATII cells or ex vivo three-dimensional lung tissue cultures reduced SASP factors and extracellular matrix markers, while increasing alveolar epithelial markers.These data indicate that alveolar epithelial cell senescence contributes to lung fibrosis development and that senolytic drugs may be a viable therapeutic option for IPF.", keywords = "Journal Article", author = "Mareike Lehmann and Martina Korfei and Kathrin Mutze and Stephan Klee and Wioletta Skronska-Wasek and Alsafadi, {Hani N.} and Chiharu Ota and Costa, {Ana Rita} and Schiller, {Herbert B} and Michael Lindner and Wagner, {Darcy E} and Andreas G{\"u}nther and Melanie K{\"o}nigshoff", year = "2017", month = aug, doi = "10.1183/13993003.02367-2016", language = "English", volume = "50", pages = "1--15", journal = "European Respiratory Journal", issn = "1399-3003", publisher = "European Respiratory Society", } . European Respiratory Journal.

Reduced frizzled receptor 4 expression prevents WNT/b-catenin-driven alveolar lung repair in chronic obstructive pulmonary disease @article{604d14284e80458aa92cbdbc90665997, title = "Reduced frizzled receptor 4 expression prevents WNT/b-catenin-driven alveolar lung repair in chronic obstructive pulmonary disease", abstract = "Rationale: Chronic obstructive pulmonary disease (COPD), in particular emphysema, is characterized by loss of parenchymal alveolar tissue and impaired tissue repair. Wingless and INT-1 (WNT)/b-catenin signaling is reduced in COPD; however, the mechanisms thereof, specifically the role of the frizzled (FZD) family of WNT receptors, remain unexplored. Objectives: To identify and functionally characterize specific FZD receptors that control downstream WNT signaling in impaired lung repair in COPD. Methods: FZD expression was analyzed in lung homogenates and alveolar epithelial type II (ATII) cells of never-smokers, smokers, patients with COPD, and two experimental COPD models by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunofluorescence. The functional effects of cigarette smoke on FZD4, WNT/b-catenin signaling, and elastogenic components were investigated in primary ATII cells in vitro and in three-dimensional lung tissue cultures ex vivo. Gain- and loss-of-function approaches were applied to determinethe effects of FZD4 signaling on alveolar epithelial cell wound healing and repair, as well as on expression of elastogenic components. Measurements and Main Results: FZD4 expression was reduced in human and experimental COPD lung tissues as well as in primary human ATII cells from patients with COPD. Cigarette smoke exposure down-regulated FZD4 expression in vitro and in vivo, along with reduced WNT/b-catenin activity. Inhibition of FZD4 decreased WNT/b-catenin-driven epithelial cell proliferation and wound closure, and it interfered with ATII-to-ATI cell transdifferentiation and organoid formation, which were augmented by FZD4 overexpression. Moreover, FZD4 restoration by overexpression or pharmacological induction led to induction of WNT/b-catenin signaling and expression of elastogenic components in threedimensional lung tissue cultures ex vivo. Conclusions: Reduced FZD4 expression in COPD contributes to impaired alveolar repair capacity.", keywords = "Cigarette smoke, Emphysema, Frizzled 4 receptor, Regeneration, Smoking", author = "Wioletta Skronska-Wasek and Kathrin Mutze and Baarsma, {Hoeke A.} and Bracke, {Ken R.} and Alsafadi, {Hani N.} and Mareike Lehmann and Costa, {Ana Rita} and Mariano Stornaiuolo and Ettore Novellino and Guy Brusselle and Wagner, {Darcy E.} and Yildirim, {Ali O} and Melanie K{\"o}nigshoff", year = "2017", month = jul, day = "15", doi = "10.1164/rccm.201605-0904OC", language = "English", volume = "196", pages = "172--185", journal = "American Journal of Respiratory and Critical Care Medicine", issn = "1073-449X", publisher = "American Thoracic Society", number = "2", } . American Journal of Respiratory and Critical Care Medicine.

Hani N. Alsafadi, Claudia A. Staab-Weijnitz, Mareike Lehmann, Michael Lindner, Britta Peschel, Melanie Königshoff, Darcy E. Wagner(2017). An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices . American Journal of Physiology: Lung Cellular and Molecular Physiology. 312. (6). p. L896--L902. American Physiological Society

Skronska-Wasek, W., Mutze, K., Baarsma, H.A., Bracke, K.R., Alsafadi, H.N., Lehmann, M., Costa, R., Stornaiuolo, M., Novellino, E., Brusselle, G.G., et al.(2017). Reduced frizzled receptor 4 expression prevents WNT/b-catenin-driven alveolar lung repair in chronic obstructive pulmonary disease . American Journal of Respiratory and Critical Care Medicine. 196. (2). p. 172-185.

Lehmann, M., Korfei, M., Mutze, K., Klee, S., Skronska-Wasek, W., Alsafadi, H.N., Ota, C., Costa, R., Schiller, H.B., Lindner, M., et al.(2017). Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo . European Respiratory Journal. 50. (2).

Alsafadi, H.N., Staab-Weijnitz, C.A., Lehmann, M., Lindner, M., Peschel, B., Königshoff, M., Wagner, D.E.(2017). An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices . American Journal of Physiology - Lung Cellular and Molecular Physiology. 312. (6). p. L896-L902.

DISSERTATION THESIS

Hani N. Alsafadi(2023). Role of the co-transcriptional regulators Yap/Taz in the normal and fibrotic lung epithelia . Lund University, Faculty of Medicine Doctoral Dissertation Series. (2023:13). Lund University, Faculty of Medicine

PREPRINT

Hani N. Alsafadi, John Stegmayr, Victoria Ptasinski, Iran Silva, Margareta Mittendorfer, Lynne Murray, Darcy E. Wagner (2022). Simultaneous isolation of proximal and distal lung progenitor cells from individual mice using a 3D printed guide reduces proximal cell contamination of distal lung epithelial cell isolations .

John Stegmayr, Hani N. Alsafadi, Wojciech Langwiński, Anna Niroomand, Sandra Lindstedt, Nicholas D. Leigh, Darcy E. Wagner (2020). Isolation of high yield and quality RNA from human precision-cut lung slices for RNA-sequencing and computational integration with larger patient cohorts .

OTHER

(2022). RNAseq of proximal and distal murine lung epithelial cells isolated with 3DLD before and after differentiation.

CONFERENCE PAPER

Sinem Tas, Deniz A. Bölükbas, Hani Alsafadi, Darcy E. Wagner(2019). 3D printing of decellularised porcine lung ECM . Society for Biomaterials Annual Meeting and Exposition 2019. 40. p. 962--962. Swiss Society for Biomaterials

CONFERENCE ABSTRACT

LSC - 2017 - Hippo-YAP/TAZ signaling is deranged in IPF @article{a3e0f54a867745e4a427186811d856e3, title = "LSC - 2017 - Hippo-YAP/TAZ signaling is deranged in IPF", abstract = "Objective: Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no cure and is characterized by deranged epithelial repair, myofibroblast activation, and excess deposition of extracellular matrix. Yes associated protein (YAP) and transcriptional co-regulator with PDZ-binding domain(TAZ), co-transcriptional activators of the Hippo pathway and proto-oncogenes, were recently found to be deranged in IPF. The cause of their dysregulation remain unknown. Hippo signaling regulates several endogenous progenitor cell functions through YAP/TAZ. We hypothesized that Hippo signaling is downregulated in IPF, resulting in increased YAP/TAZ activity.Methods and Results: We assessed normal and fibrotic (IPF or intratracheal bleomycin-treated murine) lung tissue using immunohistochemistry, qPCR, and Gene Set Enrichment Analysis to identify cell types with deranged YAP/TAZ. Distal epithelial cells and fibroblasts were found to have dysregulated YAP/TAZ activity. Hippo components were downregulated in IPF and fibrotic mice, including in murine alveolar type II cells (mATII). Secretion of YAP/TAZ targets with pro-fibrotic activity was increased in fibrotic mATII as detected by mass spectrometry proteomics. Principal component analysis using Hippo expression in the Lung Gene Research Consortium separated IPF from normal patients. Fibrotic markers, including YAP/TAZ targets and myofibroblast activation, were reduced in the bleomycin model of fibrosis and in a novel ex vivo model of early pulmonary fibrosis in human precision cut lung slices when verteporfin, an FDA approved drug and YAP/TAZ inhibitor, was used therapeutically.Conclusion: Hippo-YAP/TAZ are deranged in IPF. Pharmaceutical targeting of YAP/TAZ and or restoration of Hippo signaling may represent a new therapeutic strategy for IPF.", author = "Darcy Wagner and Hani Alsafadi and Kathrin Mutze and Rita Costa and Marlene Stein and Herbert Schiller and Naftali Kaminski and Melanie Koenigshoff", year = "2017", month = sep, day = "6", doi = "10.1183/1393003.congress-2017.OA475", language = "English", volume = "50", journal = "European Respiratory Journal", issn = "0903-1936", publisher = "European Respiratory Society", number = "Suppl. 61", } . European Respiratory Journal.