Modeling Human Multi-Organ Interaction in Disease - Cancer Cachexia (MORGI)

The convergence environment will create a platform with organ representation technology to explain communication between organs in case of disease.

Tor Erik RustenAnne Kjersti BefringGareth SullivanYoshiaki Tanaka

Project leader: Dr. Tor Erik Rusten Center for Cancer Cell Reprogramming (CanCell), Faculty of Medicine, UiO

Principal investigators:

  • Dr. Gareth Sullivan Dpt. of Pediatrics, Oslo University Hospital & HTH, Centre of Excellence, Oslo
  • Anne Kjersti Befring Associate professor, Dpt. of Public and International Law, The Faculty of Law, UiO
  • Dr. Yoshiaki Tanaka Assistant professor, Immunology, Faculty of Medicine, University of Montreal, Canada

Other important collaborators: 
Dr. Anders Strand, Philosophy, Faculty of Humanities, Dr. Teresa Zimmers, Surgery, Faculty of Medicine, Un of Indiana, USA. Dr. Anne Hope Jahren, Geosciences, Faculty of Mathematics and Natural Sciences, Dr. Tuula Nyman, Immunology, Faculty of Medicine. Dr. Nikolaj Gadegaard, Biomedical Engineering, School of Engineering, Un of Glasgow, Scotland, Dr Åslaug Helland, Cancer Genetics, Oslo University Hospital

Summary

Experimental biology provides a scientific pillar for modern medicine and relies on both in vitro cell culture and animal models. These approaches often fall short of effectively addressing multi-organ interactions in human disease, particularly when addressing human-specific biology and physiology. Induced Pluripotent Stem Cell (iPSC) technology is revolutionizing studies in human biology. iPSCs can be differentiated into organs of choice containing most resident cells, setting the stage to model human organ homeostasis and disease approximating normal physiology. However, most studies focus on understanding development, heritable and infectious disease. There is an unrealized potential to model complex multi-organ interactions under normal homeostasis and disease due to increased sensitivity of omics´ technologies, ease of CRISPRdriven genetic manipulation and monitoring of select organoids in co-culture.

This proposal brings together a consortium of expertise from several disciplines to model multi-organ interactions in disease, to build a platform of enabling technologies in this emerging research area, currently not possible to address in isolation. Integrated development of bioinformatical analysis, modeling and investigation of societal and legal aspects lay the foundation for utilization of this technology for personalized medicine and innovative therapeutic intervention. We have selected Cancer Cachexia (Greek: Kakos-“bad”, hexis-”condition”) as a model disease due to its human health implications-affecting the majority of advanced cancer patients, its inducible experimental nature and the current lack of effective human experimental models to address disease mechanisms and pharmacological intervention in vitro. In cancer cachexia, the tumor causes a cascade of systemic effects, affecting multiple organs, leading to wasting of muscle, adipose tissue and bone, liver steatosis, inflammation and metabolic reprogramming leading to death in 20% of cancer patients. We envisage that this proof of principle platform for multi-organoid interaction studies will be of utility for the larger Life Science working environment, nationally and internationally.

Primary objective

  • To unleash next generation in vitro human organoid models for multi-organ interactions in disease -using Cancer Cachexia (CC) as an exemplar of a multi-organ disease.

Secondary objectives

  • Establish “healthy” iPSC-derived organoid physiological interaction in vitro through layered complexity.
  • Define normalcy using multi-omics analysis and bioinformatic computational modeling.
  • Model a homeostasis disrupting multi-organ disease state, using CC as a paradigm with -omics and bioinformatical approaches.
  • Reveal causal mechanistic multi-organ interactions during cancer cachexia that can be targeted.

  • Explore societal, legal and ethical challenges of iPSC-derived experimental biology and personalized medicine to facilitate legislation and translational studies.

Published Nov. 9, 2021 5:00 PM - Last modified Nov. 16, 2021 10:05 AM