The Lung Bioengineering and Regeneration (LBR) Lab at Lund University focuses on growing new lung tissue in the lab for transplantation or to use this bioengineered tissue to study how the extracellular environment directs stem cell behavior. We use a multidisciplinary approach using advances in materials science (polymer design and synthesis), manufacturing (e.g. 3D bioprinting), and endogenous lung stem cells to construct this bioengineered tissue and these new models.Read more about LBR projects!
I am interested in generating lung tissue in the lab to study disease, develop new therapies and one day to be able to manufacture lung tissue in the lab for transplantation.
I was born and raised in Toledo, Ohio in the United States and received my undergraduate degree in mechanical engineering from Gonzaga University in Spokane, Washington, USA. I conducted my PhD studies in Dr. Sarit Bhaduri’s lab at the University of Toledo where I focused on using microwave processing to generate calcium phosphate nanoparticles for gene therapy and for bone tissue engineering. I went on to do my first postdoctoral training in Dr. Daniel Weiss’ lab at the University of Vermont in the Vermont Lung Center where I was an NIH T32 Fellow and developed protocols to decellularize whole lungs from different species and diseases, including human. I then moved to Munich, Germany to do a second postdoctoral training period in Dr. Melanie Königshoff’s lab at the Comprehensive Pneumology Center (a joint venture between the Ludwig Maximilians University, Helmholtz Center Munich and the Asklepios Clinic). There I focused on the derangement of distal lung epithelial progenitor cells in normal and diseased repair and regeneration.
I started my group ‘Lung Bioenigneering and Regeneration’ in 2017 at Lund University as part of the newly formed Wallenberg Center for Molecular Medicine, with a focus on regenerative medicine. I am currently an Associate Professor and Docent in the Faculty of Medicine at Lund University and head of the Lung Bioengineering and Regeneration Group. I am a Principal Investigator in the Lund Wallenberg Molecular Medicine Center as well as the Lund Stem Cell Center. My lab focuses on generation of lung tissue ex vivo for eventual transplantation and building new humanized models of lung tissue to study chronic diseases and evaluate potential therapies. My work takes a multidisciplinary approach using advances in materials science, manufacturing, and lung stem cell biology to construct these new models. I was selected in 2017 as one of the American Thoracic Society’s ‘Rising Stars of Research’ and was awarded the Carol Basbaum Award by the American Thoracic Society in 2018 – an award given to a young investigator who has demonstrated outstanding scientific achievement, mentorship, and leadership potential. My work is currently funded by the Wallenberg Molecular Medicine Fellowship and a European Research Council Starting Grant in 2018 on 3D bioprinting of lung tissue and a Swedish Research Council Starting Grant in 2018 to pursue mechanisms of repair in chronic lung diseases.
WCMM Highlight Video: “Developing therapies for patients with lung diseases”
Vetenskapens värld episode on Lung Transplantation: “Organ på väg”
Unravelling the unknown of lung fibrosis to find a treatment for the incurable disease
I come from Gaza, Palestine. I was admitted to the PhD course in August of 2018 at the group of Dr. Darcy Wagner, Lung bioengineering and regeneration (LBR). My PhD project is about finding new relevant transcriptional complexes in the lung epithelium of Idiopathic Pulmonary Fibrosis (IPF).
Lung fibrosis is a deadly disease with no available cure. Lung fibrosis can be described as an excessive injury to the lung that stiffens it preventing the barer of the disease from breathing. If you think of the lung as a balloon, lung fibrosis is like crumbling parts of the balloon continuously without stopping. Currently, the only available drugs do not help the patients, they only slow down the disease progression. These patients only survive for a few years once diagnosed. This is because we do not understand the exact causes of the disease. My doctoral studies are focused on identifying specific mechanisms related to lung stiffness in order to find new effective therapies for lung fibrosis.
Although the exact causes of lung fibrosis are unknown, many molecular events have been studied and our understanding of the disease is increasing. The lung contains as many as 40 different cell types to carry out the various functions of the lung, some of which are known as epithelial cells. Epithelial cells are located on the surface of the internal parts of the lung and they are responsible for gas exchange (i.e. breathing). These cells are heavily damaged in patients with lung fibrosis. Our research team has found two molecules to be involved in the damage of the epithelial cells, they are called YAP and TAZ, and they are known for their ability to sense changes in stiffness. In lung fibrosis, these molecules are active and are responsible for causing some of the disease characteristics. However, in normal conditions these molecules are necessary for maintaining normal functions. We are using state-of-the-arts techniques to identify the exact roles of these molecules in the different types of cells in health and disease. YAP and TAZ are like good cops that have gone rogue in fibrosis and we are investigating why so we can fix the damage they caused.
The problem with current approved drugs is that they are not specific and that is one of the reasons they do not work. Finding out the exact roles of YAP and TAZ in the lung compartments and learn how they are involved in the progression of lung fibrosis will lead us to finding highly specific drugs. Highly specific drugs will be able to stop the rogue cops without harming the good ones. Additionally, these molecules are involved in several other organs and diseases, thus knowledge gained in this research can be easily transferable to other disciplines.
Vetenskapens värld episode on Lung Transplantation: “Organ på väg”
Master of Science with emphasis in Pathophysiology and Anatomy - FMVZ- USP-Brazil. Specialist in Molecular Biology and Parasitology - IAL-SP. Bachelor of Biological Sciences UAM-SP.
Ambient air pollution accounts for an estimated 4.2 million deaths per year due to stroke, heart disease, lung cancer and chronic respiratory diseases. Around 91% of the world’s population lives in places where air pollution levels exceed WHO limits. Exposure to pollutants contributes to the development of chronic obstructive pulmonary disease COPD is lower than exposure to indoor pollutants. The WHO assumes that only 1% of COPD cases are caused by urban pollution in developed countries and the index in less developed countries goes to 2%. However, there is some evidence linking air pollution with the worsening of COPD, in addition to the fact that recognition of negative health outcomes at high levels of pollution and considering that the airways in turn the lung is the main point of entry for distribution of pollution particles to the rest of the body, since ultrafine particles are found in various organ.
The presence of air pollution is not only related to COPD but also inflammation, development of COPD, increased risk of Alzheimer’s development, and other adverse health effects including effects on fetal development through exposure of pregnant women to areas with high concentrations of pollutants. For this purpose, the evaluation of the regenerative capacity of lungs exposed or not to high concentrations of suspended material in the air is important.
The central goal of this project is to investigate where these particles end up in the lung, what they are, and how they affect lung regeneration capacity.
I am a clinician in China but also passionate about new therapies that could provide promising medicine.
I am a clinician in China but also passionate about new therapies that could provide promising medicine. I was admitted to Nagoya University in April 2019 as a Ph.D. student, majoring in stomatology and studying clinical researches focused on its clinical application as an ‘exit’ of regenerative medicine research. By participating in a Joint-Degree Program between Nagoya University (Japan) and Lund University (Sweden) in 15 months since June 2021, I had a chance to join the group of Dr. Darcy Wagner, Lung bioengineering and regeneration (LBR) as a Ph.D. student, pursuing a project about bioengineering therapy in salivary gland regeneration. Radiation therapy for malignant tumors of the head and neck can cause salivary gland dysfunction, which in turn causes a variety of serious oral diseases, such as rampant teeth and dysphagia, which seriously affect the quality of life of patients. At present, salivary gland dysfunction is mainly treated with drugs such as salivary fluid substitutes (artificial saliva) or sialogogue (pilocarpine). It not only has short curative effects, but also requires multiple long-term medications, but still has side effects that cannot be ignored. The most important thing for therapeutic effect of these treatments is closely related to the residual salivary gland functional cells after irradiation. Cell therapy is faced with deficiencies such as difficulty in extracting salivary gland stem/progenitor cells, high risks related to stem cell transplantation, and ethical issues. Other treatment methods include surgical displacement of the relevant glands in the radiation area before radiotherapy or the use of radioprotective agents, or the use of more advanced intensity-modulated radiation therapy to improve outcomes of radiotherapy. However, the former is an invasive operation; although the latter improves the accuracy of radiotherapy and may restore part of the salivary gland function, damage to the maxillofacial glands is unavoidable. In view of this, finding a more feasible treatment for salivary gland dysfunction has important clinical significance. My project is to explore the enigmatic mechanisms of radiosensitivity for salivary glands, also develop bioactive scaffolds to construct an organized branched structure with saliva-secretory function, hoping to provide more options for the recovery of salivary gland dysfunction and to repair the various disorders in its nearby tissues.
Scientific coordinator with a PhD in microbiology.
I defended my thesis and got my PhD at Lund University in 2003, after that I did a PostDoc at Malmö University Hospital, Sweden, and then worked in the private sektor for a few years. Since 2008 I am back at Lund University now on the administrative side of the research. I am deputy coordinator at Neuronano Research Center (NRC) and scientific coordinator in Lung Bioengineering and Regeneration, both at Lund University.
I am a Medical Doctor graduated from Tbilisi State Medical University,Georgia. My passion for learning basic molecular mechanisms behind disease development and pathogenesis led me to join the Lung Bioengineering and Regeneration laboratory at Lund University as a research engineer.Currently I am involved in multidisciplinary projects such as the decellularization of different tissues, the establishment of different ARDS models in large animals and a drug screening project.
Investigating the role of embryological signaling in adult lung regeneration
I´m born and raised in Skåne, Sweden and received my first undergraduate degree, an MSc in Biology from Lund University. I conducted my PhD in the Airway Inflammation and Immunology group at Lund University, where I studied vascular remodeling in lungs following allergic airway inflammation, but also neutrophil responses following infectious airway inflammation.
Following my PhD, I did a first postdoc in rheumatology (Lund University/Lund University Hospital) where I developed and described a model for systemic sclerosis/scleoderma, an autoimmune disease characterized by dermal fibrosis but commonly also in other organs such as kidney or lungs. I did a second postdoc in the Lung Biology group (Lund University) studying development of pulmonary fibrosis, mainly focusing on the effect of vascular inflammation in this process. Following this postdoc, I received a position as Assistant Professor, and during this time I started investigating the role of Wnt-signaling in development of Idiopathic Pulmonary Fibrosis (IPF).
I became a Docent (Reader/Associate Professor) in Experimental Pulmonary Medicine 2016, but realized I wanted to become an MD and work as a clinician. I thus went back to school to get a second degree, finishing in December 2020. During my education I have remained active as a researcher, seeking to merge a preclinical background with my clinical present and future.
My research focuses on embryological signaling pathways which are also essential in adult regeneration. In order to regenerate tissue after damage regenerative processes needs to be initiated, but also terminated at an appropriate time. If regeneration fails to start the tissue will not be restored, which is believed to occur in development of emphysema. However, if the regeneration is not terminated when the tissue is restored, the scar tissue will continue to accumulate resulting in fibrosis. Thus, the Swedish word “lagom” (meaning “just right”) is truly the golden standard when it comes to regeneration.
My research focuses on an embryonic signaling pathway known as Wnt/β-catenin-signaling, which is a key signaling pathway in embryological development but also in regeneration and tissue repair in adults. Wnt/β-catenin-signaling is involved in a number of fundamental biological processes, such as proliferation, migration and invasion, and are known to be dysregulated in many forms of cancer.
β-catenin-signaling is known to be decreased in emphysema and increased in pulmonary fibrosis, but the mechanisms underlying this alternate regulation is unknown. My research focuses both on how normal endogenous control mechanisms fails, as well as on the possibility to normalize the signaling by pharmacological interventions.
Biomedicine Undergraduate doing a reverse Optical Clearing project.
Assisted by Dr. Darcy Wagner´s team and Dr. John Stegmayr on developing an efficient technique to reverse solvent-based optical clearing of whole organs, allowing to support the data obtained with light sheet fluorescence microscopy using histology-based staining methods like H&E, Masson’s trichrome, or immunofluorescence.
Biomedical scientist-to-be with a clinical backbone
Hi, my name is Indra. I am a Master in Biomedicine student at Lund University and originally from Indonesia. Within the Lung Bioengineering and Regeneration Lab, I am working on my master degree project on developing a high-throughput lung ALI culture-based platform from primary human bronchial basal cells for COVID-19 prophylaxis drug screening. With my basic as medical doctor, I am naturally enticed with basic researches that is leaning on the translational side and this platform will hopefully be useful not only for the purpose of COVID-19 drug screening, but also for general use in high-throughput lung-related researches. In my free time I love to do music and I am singing together with Lunds Studentsångare as a Tenor.
Many people with end-stage lung disease have no other option than to undergo lung transplantation. There are, however, not enough donor lungs to meet clinical demand, heightening the need for new options that can increase available tissue for lung transplantation. The EU-funded 3DBIOLUNG project will focus on generating lung tissue in the lab using bioengineering approaches and explore whether new advances in 3D printing and 3D bioprinting can be a possible option for lung tissue for transplantation. To do this, it will use custom 3D bioprinters to generate constructs imitating lung tissue, 3D bioprint hybrid murine and human lung tissue models, and test gas exchange, angiogenesis and in vivo immune responses.
Sandra Lindstedt (Region Skåne, Lund University)
Lena Uller (Lund University)
In this project, we aim to develop and validate cryopreservation methods for human PCLS for use in ultimately studying SARS-CoV2 infection and evaluation of potential therapies. The development of cryopreservation techniques would allow many more experiments to be possible from a single human lung, but would also allow for the establishment of a biobank of cryopreserved PCLS (that could be used on-demand and shipped worldwide). Cryopreserved PCLS would allow testing of SARS-CoV2 in labs with access to the virus and appropriate BSL3 facilities. If fully realized, the infection model could then be run using a library of compounds with FDA/EMA approval for repurposing. As an alternative to the infection model, there has recently been reports of characterizing the late stages of infection, including characterization of the cytokine profile of patients who succumb versus those who survive. Our work previously used this approach of simultaneous exposure to multiple cytokines to develop an ex vivo model of fibrosis (Alsafadi et al. AJP-Lung 2017). This approach could be explored in parallel to identify drugs to combat lethal SARS.
As the COVID-19 pandemic progresses, it has become increasingly clear that SARS-CoV-2 disproportionately effects different patient populations and that age and underlying co-morbidities are major predictors of mortality. In parallel, it is now well acknowledged that the general population is susceptible to infection with SARS-CoV-2, but most patients remain asymptomatic and do not develop severe disease. Several potential vaccines have reached late phases of clinical trials, but even if a successful vaccine is identified soon, concerns will remain with administering a vaccine to the world population and technologies to ramp up production are still needed. During this time, it is critical to identify approaches to protect vulnerable patient populations so that society can begin to return to near normal. One potential option is to repurpose existing antiviral compounds which can prevent infection in vulnerable patients. Here, we will perform a medium throughput drug screen in primary human airway cells, a major site of SARS-CoV-2 infection, to identify approved antiviral compounds which could be repurposed for prophylactic SARS-CoV-2 therapy in vulnerable populations. Together with Cellevate AB, we have developed a new method for medium-high throughput drug screening of human airway cells which allows several hundred compounds to be evaluated on cells from individual patients. Furthermore, this assay is amenable to validation of compounds in human airway cells derived from patients with underlying co-morbidities associated with COVID-19. This approach has the potential to identify and repurpose antiviral compounds with previously established safety profiles to protect vulnerable patients until a vaccine is developed.
LBR on the news
PhD defence interview – Martina De Santis
LU Med News 2021
A new interdisciplinary co-op between researchers, healthcare and industry formed to fight the virus
LU Med News 2021
Kliniskt fysiologisk lungforskning
Lung & Allergiforum 2020
Meet this week’s Wallenberg Researcher: Darcy Wagner
LU Med News 2020
New Promising Treatment Uses Smart Nanoparticles to Target Lung Cancer
LU Med News 2020
Här skapas lungvävnad på laboratoriet
Forskning & Framsteg 2019
Darcy Wagner Receives ERC starting grant
LU Med News 2018
Four LU researchers receive ERC starting grants
LU News 2018