HMZ Seed Projects 2015

Personalizing treatment of metastatic clear cell renal cell carcinoma patients using CC-PM platform technologies

Prof. Ian Frew (UZH), Prof. Wilhelm Krek (ETH), Prof. Holger Moch (UZH/USZ), Prof. Peter Wild (UZH/USZ), Dr. Cedric Poyet (UZH/USZ)

normal tissue (left) and tumour (right)

Tumours often spread throughout the body to form new tumours at other sites, a process called metastasis. The most common form of kidney cancer, clear cell renal cell carcinoma (ccRCC), undergoes metastasis in approximately 30-50% of cases and current therapeutic regimes provide very little clinical benefit. To improve the prediction of which patients are most likely to develop metastasis and to improve therapeutic strategies to treat metastatic ccRCC, we will study the genetic landscape of ccRCC metastases by combining expertise in clinical and diagnostic pathology, genome-wide molecular analysis techniques, bioinformatics, cell biology, mouse tumour models and genetic and small molecule therapeutic screens, to form an integrated approach to tackle this important clinical problem.

Associated HMZ network: Kompetenzzentrum Personalisierte Medizin

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Functionalizing melanoma intra-tumor heterogeneity to overcome targeted therapy resistance

Prof. Mitch Levesque (UZH/USZ), Prof. Wilhelm Krek (ETH), Prof. Niko Beerenwinkel (ETH), Prof. Reinhard Dummer (UZH/USZ), Dr. Anja Irmisch (UZH/USZ)

Image Irmisch

During the last 10 years the incidence of melanoma has increased more rapidly than that of any other cancer. Up to one-fifth of patients develop metastatic disease, which is associated with a poor prognosis. With the approval of the first small molecule drugs targeting the MAPK pathway, the overall survival of these patients has improved significantly. However, after weeks to months of initial tumor regression most patients develop resistance to these personalized drugs. This HMZ Seed project aims at identifying new biomarkers and potentially targetable loci involved in melanoma progression and resistance. To achieve this, a custom-designed melanoma-specific exom sequencing panel has been developed and will be validated as diagnostic test for predictive markers. Furthermore, high-throughput screening of potentially targetable cell surface markers will be performed.

Associated HMZ network: Kompetenzzentrum Personalisierte Medizin

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Imaging the effects of contact coagulation inhibition on vascular function and neuroinflammation in Alzheimer`s disease

Prof. Jan Klohs (UZH), Prof. Simon Ametamey (ETH)

Vascular dysfunction in Alzheimer disease

Alzheimer`s disease is a complex and multi-factorial disorder, and currently there exists no effective therapy. Recent research efforts have implicated vascular dysfunction and inflammation in the etiology of the disease. Since these processes have been shown to precede the onset of dementia they constitute attractive targets for therapeutic intervention in Alzheimer`s disease. Emerging data demonstrated also an aberrant coagulation in patients with Alzheimer`s disease and mild cognitive impairment. The consequences are fibrin deposition in cerebral vessels, predisposing the vasculature to hypoperfusion and ischemia. Moreover, mediators of the coagulation system can directly affect hemodynamic function, and might impede amyloid-β clearance and foster inflammation, and might thus substantially contribute to cognitive impairment in Alzheimer`s disease. Anti-coagulation treatment has been shown to be beneficial, but increase the risk of bleeding. Given the many important pathological processes that are influenced by coagulation mediators, identifying ways to therapeutically interfere with the coagulation system without altering hemostasis might constitute an easily administrable and safe strategy to treat Alzheimer`s disease. The objective of this HMZ seed project is to investigate the role of FXII-driven contact system on AD-related vascular dysfunction and neuroinflammation in a transgenic mouse model of Alzheimer`s disease. Furthermore, we will evaluate if magnetic resonance imaging and positron emission tomography can be used to visualize these processes sensitively and specifically, and to monitor the response to therapy. The proposed investigations might expose potential novel therapeutic and diagnostic targets for Alzheimer`s disease.

Associated HMZ network: EXCITE Zurich

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Multi-parametric Ultrasound Imaging: Translating Biomechanical Non-linearity From Nuisance Into Knowledge

Prof. Orcun Göksel (ETH), Prof. Jürg Hodler (UZH/USZ), Prof. Edoardo Mazza (ETH), Prof. Marga B Rominger (USZ), Dr. Sergio J. Sanabria (ETH)

Multi-parametric Ultrasound Imaging

Diagnosis of early liver fibrosis is a major public health concern. Biopsy has long been the gold standard, however, it is invasive and suffers from sampling error. Ultrasound Elastography (USE) overcomes these pitfalls. However, non-linear characteristics of tissue are currently a major clinical confounder, yielding different measurements under different probe manipulations by the operator.

Adding robust non-linearity markers to USE can dramatically improve the reliability of liver fibrosis staging. With this aim, we will use animal liver models to characterize non-linearity using commercial and in-house developed USE techniques. We will then validate such models to ground-truth measurements through mechanical testing. In the long term, we will conduct clinical evaluation with patients undergoing USE examination and extend the scope to other organs (breast, kidney) and disease conditions.

Associated HMZ network: EXCITE Zurich

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ZurichMOVE: Wearable sensors to monitor movement quality and mobility in health care

Prof. William Taylor (ETH), Prof. Armin Curt (UZH/Baldgrist), Prof. Roger Gassert (ETH), Prof. Christian Baumann (UZH/USZ), Dr. Navrag Singh (ETH)

ZurichMove

Movement deficits due to spinal cord injury significantly impact on a patient’s quality of life. However, diagnostic tools to monitor movement quality and quantity in clinical settings are missing. The ZurichMOVE project therefore fosters the development of a next-generation inertial sensor technology, the “Joint Universities Motion Platform” (JUMP) module, for translation into clinical practice, with the goal to combine it with advanced algorithms to monitor movement deficits and recovery in patients with spinal cord injury, including wheelchair-bound patients. ZurichMOVE will bridge the gap between research and health care, and provide a user-friendly solution for care givers in the improved identification of deficits and evaluation of rehabilitation therapy.

Associated HMZ network: Zentrum für Neurowissenschaften Zürich