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Project partner:

Frau Prof. Dagmar Fischer, Lehrstuhl für Pharmazeutische Technologie und Biopharmazie, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)

Transplant rejection and the severe side effects of immunosuppression remain associated with 
relevant health and socio-economic burdens. The ultimate goal of this study is to generate 
immunologically  invisible  kidneys  by  organ  genetic  engineering  during  ex  vivo  perfusion 
towards  decreasing  their  immunogenicity.  In  this  study,  the  strength  of  allogeneic  immune 

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease whose progression is orchestrated by tissue macrophages. Their functions are regulated by two opposing lipid pathways that initiate inflammation or induce tissue regeneration. In COPD patients, macrophage lipid signaling is disrupted, resulting in uncontrolled responses and irreversible lung damage. I will use bronchoscopy samples from severe-stage COPD patients to investigate the effects of impaired macrophage lipid signaling.

Genetic information of viruses, such as HIV, Influenza and SARS-CoV-2 is formed of RNA. During infection, cells use special proteins to recognize the viral RNA inside them and destroy it. This process limits viral infection and is an important part of the innate immunity. Zinc finger antiviral protein recognizes foreign RNA and recruits endonucleases to degrade it. Endonucleases can also act on their own, targeting cellular and viral RNAs. To prevent unnecessary damage of their own RNA, cells use a protein cutting enzyme MALT1. It cuts the endonucleases so they can no longer destroy RNAs.

Targeting cancer cells while sparing healthy cells is very challenging. One strategy to solve this problem is through genetic alterations, known as mutations, which only occur in tumors but not in healthy tissues. Interestingly, some but not all of these mutations are presented to the patient’s immune system on the cell surface. Then parts of the immune system are able to recognize these presented mutations, called neoepitopes, as an abnormal structure and thus will kill the tumor cell.

Johanson-Blizzard syndrome (JBS) is caused by homozygous mutations in the UBR1 gene, encoding for an E3 ubiquitin protein ligase and therefore directly regulating the degradation of multiple proteins. Despite the identification of the genetic cause, the exact mechanism leading to the prenatal loss of pancreatic cells and other tissues has remained elusive. In my innovative JBS model, patient-specific human pluripotent stem cells will be differentiated to mature pancreatic cells by addition of specific growth factors.

Project description in easily understandable terms for the general public (800 characters incl. blanks):