MelAutim - Systems medicine investigation of melanoma and autoimmunity in the context of immune therapies

The MelAutim project aims to uncover the molecular and cellular mechanisms for the interaction of cancer and autoimmunity. In particular, it aims to identify factors that are involved in the development of new or the exacerbation of existing autoimmune diseases during immunotherapy.

The aim of the subproject 4 (SP4) is to construct and analyse the molecular interaction network connecting melanoma and autoimmune diseases (rheumatoid arthritis and inflammatory bowel disease), and screening of small-molecule inhibitors against selected checkpoints for therapy personalization. This SP 4 is divided into two phases. In the first three years, we construct disease maps with different level of regulation, i.e. transcriptional layer (transcription factors; TF), posttranscriptional (miRNAs, lncRNAs) and post-translational layers. The network will be analysed for the identification and prioritization of the core regulatory processes present at the interface of melanoma and autoimmune diseases under investigation. We will generate a multivalued logic-based model for the core regulatory processes and perform in silico perturbation experiments to identify critical checkpoints regulating adverse events responsible for Connecting Melanoma and autoimmune diseases using molecular interaction map (MAMIM) developing comorbidity phenotypes in melanoma patients. In the second phase of this subproject, we will perform molecular docking and molecular dynamics simulation studies for prioritized checkpoints regulating comorbidities and develop pharmacophore models for screening of large drug and nutraceutical libraries to identify small molecule inhibitors. These small molecule inhibitors will be connected to the molecular interaction network designed in the first phase to develop a drug interactome. We will develop methods to integrate patient data with drug interactome for designing personalized therapy.

Related publications

LncRNA-SLC16A1-AS1 induces metabolic reprogramming during Bladder Cancer progression as target and co-activator of E2F1

Logotheti S, Marquardt S, Gupta SK, Richter C, Edelhäuser BAH, Engelmann D, Brenmoehl J, Söhnchen C, Murr N, Alpers M, Singh KP, Wolkenhauer O, Heckl D, Spitschak A, Pützer BM

Theranostics 2020; 10(21):9620-9643.

An integrative network-driven pipeline for systematic identification of lncRNA-associated regulatory network motifs in metastatic melanoma

Singh N, Eberhardt M, Wolkenhauer O, Vera J, Gupta SK

BMC bioinformatics 21 (1), 1-17