Apical-out human airway organoids-on-a-chip derived from iPSCs for studying bacterial infections

Multi-drug resistant bacterial infections, such as Pseudomonas aeruginosa represent a significant global health care burden and disproportionately impact patients who are immuno-comprised, which make them more susceptible to opportunistic pathogens. These infections impact a broad range of patients, including those with chronic diseases such as diabetes, cancer, organ transplant recipients, and those with chronic respiratory diseases. 

P. aeruginosa has been listed on the World Health Organization’s list of priority pathogens for at least a decade and was recently included as one of 15 pathogen families listed on the WHO’s Bacterial Priority Pathogens List (BPPL) 2024. There is an urgent need to increase research on P. aeruginosa to identify new therapies.

This project aims to develop a new humanized model of airway organoids, which represent a more physiological path of infection. We will generate apical-out airway organoids (i.e. the upper layer of the epithelial cells will face out towards the media instead of inwards like conventional organoids). We will utilize induced pluripotent stem cells (iPSCs) to derive proximal and/or distal airway progenitor cells and develop custom microfluidic devices for longer term culture with live bacteria. The use of iPSCs is particularly important in this proof-of-concept grant as it opens up future possibilities to study more diverse patient phenotypes, especially among those patients who have underlying comorbidities and who may not undergo invasive bronchoscopy procedures where primary airway cells could be sourced (e.g. diabetes, cancer patients, etc).

IGNITE Fellow - Shahram Parvaneh 

Shahram Parvaneh completed his PhD in Immunology at the University of Szeged, Hungary, in the Regenerative Medicine and Cellular Pharmacology Laboratory. His doctoral research focused on cancer biology, investigating the effects of bile acids on pancreatic cancer tumorigenesis and developing a 3D bioprinted tumor model to study the role of adipose-derived mesenchymal stem cells (ADMSCs) in tumor microenvironment–driven chemoresistance. He integrated transcriptomic and proteomic approaches to uncover the molecular mechanisms underlying therapy resistance and tumor–stroma interactions.

Before his PhD, Shahram earned a BSc in Clinical Laboratory Sciences and an MSc in Medical Immunology. He has broad experience in protein purification, immunochemistry, bioconjugation, biomaterial-based tissue engineering, and stem cell biology across both academic and industrial settings.

Since 2023, Shahram has been working as a research engineer in the Wagner Lab - Lung Bioengineering and Regeneration Group - at Lund University. 

Shahram is currently an IGNITE Fellow the Wagner Lab, where he is developing a humanized airway organoid model to study Pseudomonas aeruginosa, a WHO priority pathogen that urgently requires new therapeutic strategies. 

His project involves creating apical-out airway organoids derived from induced pluripotent stem cells (iPSCs) to mimic physiological infection routes and integrating microfluidic systems to enable long-term co-culture with live bacteria.

Main Principal Investigator

• Darcy Wagner

Co-supervisor

• Lisa Påhlman