Microstructural and metabolic magnetic resonance imaging for cardiac regeneration therapy
Prof. Sebastian Kozerke (UZH/ETH), Prof. Simon Hoerstrup (UZH/USZ), PD Dr. Maximilian Emmert (USZ), Dr. Christian T. Stoeck (UZH/ETH)
Although survival after Heart failure (HF) diagnosis has improved, still 50% of the patients die within five years after diagnosis. Treatment options of HF depend on many factors, but for end-stage HF, heart transplantation is often the only choice. Due to general shortage of donor organs and contraindications in the individual patient, alternative approaches are pursued. Stem-cell therapy has been proposed as a potential intervention to stimulate tissue regeneration in chronic HF. However, measures of success have been restricted to global diagnostic markers. Recent advances in imaging technologies have enabled real-time imaging of microstructural and metabolic information of the beating heart. The objective of this HMZ Seed Project is to validate this magnetic resonance imaging methodology in an animal model of cardiac regeneration therapy and to translate it into a clinical protocol.
Associated HMZ Network: EXCITE Zurich
Formation and activation of brown fat in cancer cachexia
Prof. Markus Stoffel (ETH), Prof. Giatgen Spinas (USZ), Prof. Christian Wolfrum (ETH)
Obesity and associated metabolic disorders are highly prevalent in westernized countries and new strategies to reduce body weight are needed. A new potential approach to fight adipositas is the activation of brown fat. In contrast to the classical lipid-storing white adipose tissue, brown adipose tissue dissipates energy. Recent studies showed that white fat could be transformed into brown fat, a mechanism referred to as “adipose tissue browning”. It readily occurs in cancer cachexia, a paraneoplastic wasting syndrome characterized by atrophy of fat tissue and skeletal muscle and that is thought to affect up to 50% of patients in late stage cancer. To study the formation and activation of brown fat, two approaches are followed: one aims at identifying the genetic factors that underlay the highly heterogenic distribution of brown fat in humans. The other will use a model of cancer cachexia to identify potential systemic factors that induce brown adipocyte activation and formation.
The gut microbiota: shielding against infection, but sensitive to intervention?
Prof. Wolf-Dietrich Hardt (ETH), Prof. Gerhard Rogler (USZ), Prof. Uwe Sauer (ETH), Prof. Christian von Mering (UZH)
The gut harbors a dense microbial community (microbiota) with numerous functions in health and disease, including protection from enteropathogenic bacteria. This so-called “colonization resistance” will be investigated in the present HMZ Seed Project. Lactulose, a disaccharide routinely used in diagnostic procedures, increases the susceptibility to diarrheal infections caused for example by Samonella spp.. By using an indicator-strain approach, it will be examined if lactulose disrupts the colonization resistance. To this end, growth of Escherichia coli, a normal component of the gut microbiota, is monitored upon lactulose treatment. In a mouse model, the indicator-strain approach will be verified and further investigated.
Associated HMZ Network: Node Infection and Immunity
Comprehensive molecular profiling towards biomarkers of acute aortic dissection
Prof. Manfred Claasen (ETH), Prof. Arnold von Eckardstein (UZH), Dr. Felix Schönrath (USZ)
Acute aortic dissection (AAD) is associated with a high morbidity and mortality. Clinical imaging provides a robust and effective basis for diagnosis of AAD, but is associated with high performance costs and inconvenience for unstable patients. Up to now, easily accessible and cost-effective blood tests play only a minor role in the assessment of AAD due to a lack of clinically relevant biomarkers. This HMZ Seed Project aims at the identification of such biomarkers. To achieve this, transcriptome and proteome analyses of aortic tissue of AAD patients and respective control groups will be performed and analyzed by bioinformatics. Subsequent biochemical quantification in blood samples will validate these results.
Making induced pluripotent stem cells safe for regenerative medicine and fertility restoration therapies
Dr. Cameron Moshfegh (ETH), Dr. Benedikt Weber (UZH/USZ), Prof. Viola Vogel-Scheidemann (ETH), Prof. Simon Hoerstrup (UZH/USZ)
Stem cell therapy has enormous potential in regenerative medicine. One of the many possible applications is the restoration of the fertility of young patients who underwent cancer therapy. Pluripotent stem cells harbor the greatest potential, as these cells are able to form all types of somatic cells as well as germ cells. Meanwhile, it is possible to generate induced pluripotent stem (iPS) cells from blood samples and without genetic modification. But their intrinsic tumorigenicity forms a major obstacle for medical applications. In this HMZ Seed Project, a new method to chemically induce pluripotent stem cells that is supposed to prevent transplanted iPS cells to differentiate into tumors, will be tested.