Projektdaten

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Trans-CPA - A transdisciplinary approach to the identification of personalized biomarkers and therapeutic targets for chronic pulmonary aspergillosis

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The expanding population of patients with chronic obstructive pulmonary disease (COPD) is at high risk of developing chronic pulmonary aspergillosis (CPA), an infection with devastating consequences to the lungs. Risk of CPA among COPD patients varies remarkably, even considering similar predisposing clinical conditions and environmental exposure. There is therefore a pressing demand for improved risk prediction and individually tailored prophylaxis, diagnosis and treatment, including new targets for drug development. Recent studies have implicated genetic factors in fungal disease but have provided little insight into the nature of the genetic and, more importantly, biological mechanisms underlying susceptibility to infection. Genetic analysis of individual molecular traits and systematic functional phenotyping offer a promising strategy for investigating variation in the propensity to develop CPA. TRANS-CPA proposes a transdisciplinary approach to identify novel biomarkers and therapeutic targets for personalized medical interventions in COPD patients at-risk of CPA. We aim to identify interindividual regulatory variation that modulates fungal-sensing transcriptional responses, to annotate the molecular and functional phenotypes through which regulatory variants control antifungal immunity, and to dissect their contribution to the development of fungal infection. Using cutting-edge research tools that combine genome-wide genotyping and transcriptomics, immunological and metabolic profiling, and advanced lung-on-a-chip model systems and patient samples, this ambitious proposal will establish a systematic understanding of the molecular and biological processes that define individual susceptibility to CPA. By deciphering such mechanisms, TRANS-CPA will contribute significantly to clinical practice in pulmonary medicine by opening new horizons and laying the foundations for personalized approaches based on individual patient profiles.