Clinical Research Priority Programs

The Clinical Research Priority Program (CRPP) is a part of the Faculty of Medicine's efforts to promote strategic areas of research for the Faculty of Medicine and University Medicine Zurich. The CRPP builds on the University's excellent reputation in research and teaching, and attach great value to knowledge exchange between basic research, applied research and clinical care. The program's goals include promoting selected – primarily clinical – areas of research in University Medicine and establishing effective networks within them. In addition, the programs are committed to supporting junior scholars.

 

A new series of CRPP was launched at the University of Zurich (2019 - 2021):

CRPP Pain

Pain - from phenotypes to mechanisms

University of Zurich, Balgrist University Hospital, UniversityHospital Zurich

Prof. Dr. Armin Curt, Prof. Dr. Hanns Ulrich Zeilhofer

Chronic pain continues to pose a major, unmet challenge for modern medicine with tremendous global healthcare costs. Independent of the diverse clinical presentations of chronic pain conditions, a common underlying pathophysiological mechanism is sensitization along the nociceptive neuraxis. The goal of the CRPP Pain is the identification of pathophysiological differences and commonalities across different diagnostic chronic pain entities by dissecting the impact of peripheral, spinal and supra-spinal sensitization processes. The vivid exchange between different clinical and basic research disciplines to tackle this challenge offers a promising venue for future personalized targeting of disorder-specific mechanisms in chronic pain patients.

www.crpp-pain.uzh.ch

CRPP HYRENE

HYRENE - HYpertension REsearch NEtwork

University of Zurich, UniversityHospital Zurich

Prof. Dr. Felix Beuschlein, PD Dr. Christina Rossi

High blood pressure is the world's leading risk factor for premature deaths and disability-adjusted life years. Lifestyle interventions and drug treatments achieve normalization of blood pressure in only half of the patients. In about 20% of the remaining cases, blood pressure is not adequately controlled despite the use of antihypertensive medicaments. This condition increases patient’s risk for stroke and myocardial infarction. The CRPP HYRENE aims to identify key factors for the development of therapy resistance of hypertension that may become modifiable targets for improved and individualized treatment of affected patients. To achieve this goal, the CRPP aims to improve the diagnostic tools that can identify pathophysiological mechanisms underlying the development of therapy resistance. The success of the program is based on the convergence of clinical, pre-clinical and applied scientific research into a joint consortium that promotes the implementation of the scientific and technological advances of the preclinical research into patient care.

www.hyrene.uzh.ch

CRPP CGPD

Comprehensive Genomic Pathogen Detection

University of Zurich, UniversityHospital Zurich

Prof. Dr. Nicolas Müller, Dr. Michael Huber, Prof. Dr. Alexandra Trkola

The vast variety of infectious pathogens remains a challenge for clinical diagnostics necessitating multiple tests for different pathogens for a conclusive diagnosis. This CRPP will probe Comprehensive Genomic Pathogen Detection (CGPD) as a broad, rapid and inexpensive analysis for viral and microbial pathogens. Using high-throughput metagenomic sequencing, the CRPP will assess clinical cases with suspected infectious etiology and compare CGPD to conventional diagnostic tests. By employing CGPD in diverse clinical settings the CRPP will gain valuable insight how diagnostics of infectious pathogens can be advanced and which options for disease management and treatment rise from the comprehensive assessment of pathogens.

www.cgpd.uzh.ch

CRPP Synapse & Trauma

Targeting novel synaptic pathways in trauma-related psychiatric disorder

University of Zurich, University Hospital of Psychiatry Zurich

Prof. Dr. Dominik Bach

Psychological trauma and early-life adversity are major risk factors for various psychiatric disorders. Recommended treatment is by psychotherapy, which seeks to modify aversive memories, but leaves a significant proportion of patients symptomatic. At the same time, our understanding of synaptic biology has increased exponentially. The CRPP Synapse & Trauma investigates possibilities to combine psychotherapy with pharmacological agents. It focuses on the molecular pathways involved in degrading old, and shaping new, synaptic connections. In humans, the CRPP will explore candidate drugs already approved for other indications. Using in-vitro and animal models, the CRPP seeks to decipher signalling pathways and elucidate novel drug targets.

www.synapsetrauma.uzh.ch/en

CRPP ImmunoCure

Targeted Cancer Immunotherapy

University of Zurich, UniversityHospital Zurich

PD Dr. Patrick Roth, Prof. Dr. Markus Manz

Immunotherapy represents the key promising area of novel therapeutic approaches to cancer. The CRPP ImmunoCure aims at establishing and expanding the concepts of bispecific antibodies and chimeric antigen receptor (CAR) T cells as cornerstones of a “targeted therapy development and technology immunotherapeutic platform” in Zurich that includes (i) monoclonal antibody engineering, (ii) CAR cell engineering, (iii) in vivo modeling and 3D imaging of CAR T cell traveling and target cell killing; and (iv) profiling of immune cell responses. The CRPP will explore these technologies in two “targeted therapy lead disease focus programs”, one on brain tumors and one on hematologic stem cell malignancies.

CRPP Precision Hematology / Oncology

Next Generation Drug Response Profiling for Personalized Cancer Care

University of Zurich, University Children's Hospital Zurich, UniversityHospital Zurich

Prof. Dr. Jean-Pierre Bourquin

Despite rapid progress in cancer genomics and molecular disease classification, it remains difficult to identify actionable targets and predict response to drugs based on this information. New approaches that identify cancer vulnerabilities and predict the response to treatment based on pre-treatment testing of individual cancer cells could improve response rates, reduce unnecessary treatments, and significantly increase cost-effectiveness. Based on strong proof-of-concept data, the CRPP hypothesizes that critical predictive and mechanistic information can be obtained from direct functional drug response screening of primary patient samples. The CRPP joins forces to develop a clinical platform for next-generation precision medicine at UZH, to apply drug response profiling to personalize treatment of patients and investigate unexpected vulnerabilities at depth.

www.crpp-pho.uzh.ch/en

CRPP Stroke

The interplay of microcirculation and plasticity after ischemic stroke

Universit of Zurich, UniversityHospital Zurich

Prof. Dr. Andreas Luft, Prof. Dr. Susanne Wegener

Stroke is a frequent and devastating disease. The majority of survivors remains disabled, despite significant progress in acute treatment. Self healing mechanisms of the brain exist and could open treatment avenues for those who survive with brain injury. However, knowledge about these mechanisms is still incomplete. The researchers of the CRPP Stroke hypothesize that hypoperfusion in the acute phase of ischemic stroke is the trigger for self healing mechanisms, specifically for plasticity in intact brain surrounding the injury. Through a collaboration between neurology, neuroradiology, neurosurgery and neuropathology hey test this hypothesis in parallel research in humans and animal models.

www.stroke.usz.ch/forschung/kfsp-stroke

CRPP BacVivo

Precision medicine for bacterial infections

Universit of Zurich, UniversityHospital Zurich

Prof. Dr. Annelies Zinkernagel, PD Dr. Barbara Hasse

Recurrent or chronic infections are an unsolved clinical problem despite the availability of antibiotics to which the bacteria are susceptible. Bacteria isolated from recurrent or chronic infections may be in a dormant, non-growing state, tolerate antibiotic challenges and are capable of resuming growth. These bacteria are called persisters. Persisters are protected from antibiotics, which target processes in growing cells. The CRPP BacVivo aims to establish a multidimensional assessment of individual patients with bacterial infections combining clinicians, clinical microbiologists and computational biologists/scientists in order to improve diagnosis, treatment and outcome of chronic bacterial infections, namely endovascular, bone and prosthetic joint as well as skin and soft tissue infection.

www.bacvivo.uzh.ch

CRPP Praeclare

Clarification of genetic variants for personalized prenatal and reproductive medicine

Universit of Zurich, UniversityHospital Zurich

Prof. Dr. Anita Rauch

Developmental disorders affect approximately 7% of offspring and are commonly caused by genetic mutations. The identification of a definite genetic diagnosis enables informed management of the pregnancy as well as further reproductive choices, such as preimplantation diagnostics. Moreover, there is an increasing demand for extended preconception carrier screening. While technically feasible, implementation into clinical practice is hampered by the large amount of variants of unknown significance detected by such untargeted screening approaches. The aim of the CRPP Praeclare is therefore to improve reproductive genetic testing by further exploring the genetic landscape and variant pathogenicity of development disorders.

www.praeclare.uzh.ch

CRPP AI Oncological Imaging

Artificial Intelligence in oncological Imaging Network

Universit of Zurich, UniversityHospital Zurich

rof. Dr. Jürg Hodler, Prof. Dr. Matthias Guckenberger

Artificial Intelligence (AI) methods are rapidly developing in many areas of everyday life.  First applications are also seen in medicine, and AI is expected to further revolutionize the work of many physicians. This CRPP develops applications of AI in oncological imaging, i.e. the diagnosis and treatment of cancer patients. Improvements are expected in two directions. First, AI techniques facilitate automation and standardization of labor-intensive routine tasks of physicians. Second, AI algorithms allow for quantitative analysis of medical images and facilitate detection of image features not perceivable to the human eye. Thereby, AI algorithms may improve cancer diagnosis and therapy.

www.crpp-ai-oncology.uzh.ch

CRPP Precision MS

Implementing Precision Medicine in Multiple Sclerosis

Universit of Zurich, UniversityHospital Zurich

Prof. Dr. Roland Martin

Multiple sclerosis (MS) is a prototypic autoimmune disease, which leads to damage of the central nervous system. Due to its disease heterogeneity, it serves as ideal example to pursue research in personalized medicine and to translate existing knowledge and novel findings into clinical routine. Therefore, the CRPP PrecisionMS will address two main aims: 1) To develop individual disease/risk profiles and markers for specific pathomechanisms that can be used for treatment decisions and as measures for innovative clinical trials. 2) To apply these measures in the routine clinical setting to guide patient care as well as for testing novel treatments.

www.precisionms.uzh.ch

CRPP ImmuGene

Gene Therapy for Severe Immunodeficiency

Universit of Zurich, University Children's Hospital Zurich

Prof. Dr. Janine Reichenbach, Prof. Dr. Martin Jinek

Gene therapy aims to provide break-through therapeutic options targeting severe genetic diseases. Based on expertise from previous first-in-man clinical gene therapy at University Children’s Hospital, and world-class research on vector development and gene editing at University of Zurich, the CRPP ImmuGene will be the seed of a translational gene therapy competence center.  In the kick-start phase, the CRPP will realize a first-in-man clinical trial for the immunodeficiency chronic granulomatous disease, translating a next-generation lentiviral vector. Parallel development of CRISPR-based gene correction approaches will enable preparation of a clinical gene-replacement trial to be realized in the follow-up phase.

CRPP CYTIMM-Z

Zurich initiative on novel cytokine-directed treatments for immune dysregulation

Universit of Zurich, UniversityHospital Zurich, University Children's Hospital Zurich

Prof. Dr. Onur Boyman, Prof. Dr. Jana Pachlopnik

Cytokines that share the common γ chain receptor, particularly, interleukin (IL)-2, IL-7 and IL-15, play crucial roles in the homeostasis, activation and control of immune responses. In immune-mediated disorders these homeostatic processes and cytokines are dysregulated. This CRPP will study the homeostatic mechanisms and cytokines in two diseases, in which dysregulation of cytokine pathways very likely plays an important role in the pathogenesis: hemophagocytic lymphohistiocytosis and systemic lupus erythematosus. We hypothesize that treatments modulating homeostatic cytokines can be harnessed to restore a balanced immune homeostasis, which has several advantages over the currently used immunosuppressive treatments.

http://www.immunologie.usz.ch/forschung