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Clinical Research Priority Programs

Getting to Grips with the Blood and Immune System

The Human Hemato-Lymphatic Diseases Clinical Research Priority Program (CRPP) is all about finding better therapies for serious blood disorders and infections. The CRPP is one of the University of Zurich’s eleven clinical research priority programs. UZH News is presenting a series of features on these programs.
Stefan Stöcklin
Better models: Markus G. Manz und his team are reshaping the human immune system in animals. (Image used with permission)

Almost all humans harbor the Eppstein-Barr virus without even realizing it or developing any symptoms of illness. But sometimes this persistent virus breaks out and causes a lymphoma, a tumor of the lymphatic system – the name given by physicians to the network of organs, vessels and cells building the immune system. Closely connected with it is the way mature blood and immune cells are developing from blood-forming stem cells in the bone narrow. Spontaneous mutations in these precursor cells can lead to the development of dangerous diseases such as leukemia.

The Human Hemato-Lymphatic Diseases Clinical Research Priority Program aims to find enhanced methods for treating diseases of the lymphatic and blood-forming system. “We’re working on predictive models for investigating human disease and therapeutic mechanisms,” explains Markus G. Manz, Professor of Hematology and Director of the Hematology Clinic at University Hospital Zurich.

From man to mice

That’s no easy undertaking: Besides the brain, the immune system is probably the most complicated organ in the entire human body, with different types of cells and messengers working together in a complex, interconnected web, generating customized immune responses to pathogens and foreign antigens. This defensive system has evolved over thousands of years, and is “human” in the most profound sense of the word.

This creates a problem for researchers, as in many cases results from animal models aren’t directly transferable to humans. The scientists on the program have therefore developed appropriate model organisms with a similar immune system to humans (see links). This way, the researchers led by Markus G. Manz have been able to successfully conduct pioneering experiments resulting in mice with key components of the human immune system.

Models for various groups

“These animal models are a good way of getting a better understanding and testing preclinical therapies,” says hematologist Manz. Groups of researchers in different fields have joined forces under the CRPP to harness these new possibilities. Manz and his team are using model organisms to research disorders such as myelodysplastic syndrome, a condition where blood cells in the bone marrow no longer mature properly.

Christian Münz, Professor of Experimental Immunology, is analyzing the molecular processes in the immune system that activate the Epstein-Barr virus. Pediatric oncologist Jean-Pierre Bourquin is using the animal models to study the biology and treatment of acute lymphatic leukemia (ALL), another type of blood cancer triggered by mutations in precursor blood cells. Here preclinical experiments are being used to test the most efficient therapies for patients.

Another group led by Roberto Speck, Professor of Infectious Diseases, is researching new ways of treating HIV infection by generating immune cells that are resistant to the virus. And finally, Adriano Aguzzi, Professor of Neuropathology, is looking into a special class of dendritic cells that take up antigens and can activate the immune system, as well as protein deposition disorders of the immune and nervous systems.

While the research groups are focusing on different pathological processes, what the researchers at the University Hospital, the Children’s Hospital and the University of Zurich all have in common is their proximity to clinical practice: “Above all we want to use the new insights to help accelerate clinical research,” says Markus G. Manz.