Systems medicine of pulmonary arterial hypertension - SYMPAThIE study -

• Applicant: Dr. Jonas Schupp
• Subject Area: Pneumology, Thoracic Surgery
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 493930154

Pulmonary arterial hypertension (PAH) is a fatal chronic lung disease. All approved PAH drugs only delay the progression of the disease; accordingly, new therapeutic approaches are being sought. Within the framework of the DFG proposal "Systems Medicine of Pulmonary Arterial Hypertension", the SYMPAThIE study, the innovative technologies "Single Cell RNA Sequencing" and "Spatial Transcriptomics" will be used to find novel therapeutic approaches. "Single Cell RNA Sequencing" enables the analysis of mRNAs ("messenger ribonucleic acid" - messenger molecules that carry the genetic information about the structure of proteins) in hundreds of thousands of individual cells. "Spatial transcriptomics" allows the study of mRNAs in tissue, i.e., with spatial resolution. Together, these technologies offer previously unauthorized insights into (diseased) cells, the smallest living units in humans. During my PostDoc at Yale University, I created the human lung endothelial cell atlas, as well as the pulmonary fibrosis cell atlas (including first description of aberrant basaloid cells). The aforementioned endothelial cell atlas will be used as a reference to generate a PAH cell atlas, i.e. gene expression profiles of hundreds of thousands of individual cells. This will then allow identification of aberrant cell populations and their pathological gene expression profiles in PAH lung. Hereafter, the characteristic histopathological abnormality of PAH - the plexiform lesions - and the pathologically altered pulmonary arterial wall in PAH will be deciphered using "Spatial Transcriptomics". Based on this work, gene regulatory networks and novel molecular PAH therapeutic targets will be developed that normalize pathological intercellular communication. The necessary prerequisites for carrying out this challenging project are available at the Hannover Medical School with Germany's largest lung transplant center. The PAH cell atlas, as well as the spatially resolved PAH gene expression profiles, will provide valuable scientific resources that will potentially lead to novel, urgently needed therapeutic approaches.

• DFG Programme: Research Grants