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The Doctoral Programme
“Immune Modulation in Respiratory Diseases”

Research questions and concept of RESPImmun

The goal of RESPImmun is to provide an excellent multidisciplinary graduate training. The program focuses on lung diseases and immunomodulatory mechanisms, both are highly relevant for medical research and patient care. Respiratory diseases affect over several hundred million people and rank second only to cardiovascular diseases in terms of mortality, incidence, prevalence, and socio-economic burden. According to the latest WHO estimates around 235M people worldwide suffer from asthma, 64M from chronic obstructive pulmonary disease (COPD) and millions have allergic rhinitis or other — often — underdiagnosed chronic respiratory diseases (Link). Furthermore, asthma could be associated with COPD. In general, patients with CLD are at a high risk of developing cardiac diseases. Development of pulmonary hypertension (PH) is a life-threatening complication of advanced CLD and is associated with reduced exercise ability and increased oxygen desaturation. PH patients have significantly worse outcome and risk of mortality. Furthermore, lung cancer often co-occurs in patients with COPD and represents the most common cause of cancer death in humans. While in Europe, age-corrected incidence rates have been decreasing in men, they are still increasing in women. The 5-year overall survival, including operated stage-I cancer is < 18 %. Moreover, patients with CLD are more susceptible for infections such as SARS-CoV-2 thus understanding these diseases might help to combat future pandemics.

Inflammation and altered immune responsiveness are common theme underlying all respiratory disorders. The immune system can be viewed as a double-edged sword: In the physiological context, inflammatory processes are concerned with host defense against pathogens, healing and lung tissue regeneration. Under pathological conditions, inflammation may turn against the host, causing extensive tissue damage, and can promote disease progression leading to cellular dysfunction, chronic disease or even cancer. Moreover, in certain pathologic conditions alterations in distinct immune cell subtypes might potentiate the disease resulting in a vicious cycle. Current treatment strategies help to control symptoms and increase the quality of life; however, do not cure the underlying disease. Thus, RESPImmun addresses diseases that affect the lung, with a focus on its functional compartments such as the respiratory tract, interstitium and vascular bed. RESPImmun focuses on deciphering the interplay between immune system / inflammatory components and structural components and shape new diagnostic and therapeutic concepts. The inherent diversity of approaches and methodologies will impart the students with a deep knowledge of the most relevant areas of inflammation, which goes far beyond their individual projects. To account for the complexity of respiratory diseases we propose here 13 projects that are divided into three areas (Area 1: Chronic rhinosinusitis (CRS) and Asthma; Area 2: Pulmonary hypertension due to COPD / PF; and Area 3: Lung cancer). As different lung diseases can co-exist in patients, comprehensive therapeutic strategies could lead to better patient outcomes.

Here, we aim to investigate inflammatory processes and inflammatory mediators as common denominators in chronic lung disease (CLD). Even though CLD encompasses several different entities, often the underlying inflammatory cells and their mediators overlap. The resulting disease manifestation depends on the lung compartment or affected target cell. By concentrating on common denominators, we will efficiently combine resources and knowledge to better delineate the pathomechanisms underlying CLD. Based on this concept several projects have been proposed and outlined. By applying -omic approaches (transcriptomics, proteomics and microbiomics) on samples from different CLD (Chronic rhinosinusitis-CRS, asthma, chronic COPD-PH, fibrosis-PH and cancer) we will identify common and divergent modifiers. Additionally, by performing and comparing the immune cell profiles from multiple diseases we will identify previously unrecognized interactions. This will enable us to determine similarities and differences in how the same cell influences development of different CLD. All acquired data will be available for all the members of the consortium to better understand the complexity / similarity of the inflammatory components and potentially to discover new pathogenic mediators and therapeutically relevant biomarkers (Figure 1). All projects are supported by a common biobank containing more than 5 million human tissue and serum samples, translational (animal) and -omics platforms as well as system biology approaches which will promote knowledge exchange.

All proposed projects are described in full detail on our website at the faculty page.
A list of all projects with principle investigators and Co-PIs is given at the projects page.

Figure 1: RESPImmun Projects. CLD encompasses several different entities, but the underlying inflammatory cells and their mediators offen overlap. Abbreviations: SCFA (short chain faty acids), FFA (free faty acids), LPC (lysophosphatidy-lcholines), BM (basement membrane), PKC2 (Phosphoenolpyruvate carboxy kinase 2), M1/M2 (macrophages M1/M2, MGL (monoglyceride lipase), TME (tumour microenviroment), MPO (myeloperoxidase), BMP7 (Bone Morphogenetic Protein 7). Arrows indicate bidirectional flow of the information (to and from the platform) and flow of the information between areas.