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2005 Mannheim gene

Fokko van der Woude (1953 - 2006)

Fokko van der Woude was born on September 30, 1953 in Leeuwarden  in the Netherlands.

After graduating from high school, he would have liked to study violin at the conservatory. But the family lives in modest circumstances, and his father wants his talented son to learn a profession with which he can later support a family. Fokko complies and studies medicine in Groningen from 1970 to 1977. He always remained faithful to the violin, which became his favorite hobby.

The medical assistant van der Woude completed his clinical training at the Center for Internal Medicine at Groningen University Hospital from 1977 to 1982. He met his wife Riet in the university orchestra, and they married in 1978. In 1979, twins Joanne and Diane are born.

With his license to practice as an internist, he begins his scientific career. He becomes  assistant in nephrology at the University of Groningen and trains from 1982 to 1985 to become a nephrologist, a specialist in renal medicine. While still in residency, he began researching immune complexes. He discovered that the serum of patients suffering from "Wegener's granulomatosis" (an inflammatory rheumatic autoimmune disease of the vascular system with frequent kidney inflammation) adheres to the neutrophil granulocytes in a very special way. Neutrophil granulocytes form the largest subgroup of white blood cells and are part of the cellular immune system.

This leads to the discovery and first description of the detection of anti-neutrophil cystoplasmic antibodies in vasculitis, ANCA for short, in 1985. Vasculitis refers to vascular inflammation caused by  autoimmunological processes .(1)

With this discovery, he becomes internationally known in expert circles. The term "ANCA" is associated with the name Fokko van der Woude. The laboratory test developed on the basis of his research is still the worldwide standard in the diagnosis of vascular inflammations (vasculitides). For patients, this means easier and faster detection of certain types of vasculitis than was previously possible. Now, a biopsy is no longer required for diagnosis; instead, the disease can be diagnosed serologically and its course can be monitored.

Fokko van der Woude's research is fundamentally changing the understanding of vascular disease. This is visible, among other things, in today's official nomenclature and classification of these syndromes into ANCA-associated and non-AnCA-associated vascular diseases.(2)

In 1985, he published his doctoral thesis on immune complex formation in glomerulo-nephritis, a specific form of kidney inflammation, and factors influencing vasculitis, and also published the description of the detection of ANCA. (3)

Dr. van der Woude receives a post doc fellowship  and works in the Department of Pediatric Nephrology (kidney diseases of childhood) at the University of Minnesota (USA) until 1987. During this time he is able to establish a wide range of international contacts. After returning from the USA, he became a senior physician in nephrology at the renowned University of Leiden and headed the kidney and pancreas transplantation program. He researched the role of brain death in determining transplant survival.

In 1995, Prof. van der Woude was appointed Director of V. Medicine and Full Professor of Internal Medicine at Mannheim University Hospital. His clinical and scientific work focused in particular on kidney diseases caused by diabetes, transplantation medicine, and metabolic and vascular diseases.

On June 26, 1997, Prof. van der Woude founded the German Kidney Foundation together with his wife Riet and Prof. Carl-Heinrich Esser in Mannheim.  In the Netherlands and also in the USA, van der Woude had become acquainted with the beneficial work of kidney foundations. In Germany, however, there was no such institution. With great personal commitment on the part of its founders, the German Kidney Foundation succeeds in raising funds for nephrological research as well as social work for dialysis patients. It also funds scholarships and conducts educational work about kidney disease throughout Germany.

Kidney disease is one of the most common late effects of diabetes. It affects nearly 40% of all people with diabetes. If diabetic nephropathy is not detected and treated in time, it can lead to kidney failure, requiring regular dialysis or even a transplant.

But why do most diabetics escape this? A large Turkish family is found to have a high incidence of diabetes with the late consequence of nephropathy. So could heredity play a role here? If van der Woude makes a  clinical observation, he tries to find out the pathophysiological basis in the laboratory, just as he conversely brings knowledge gained in the laboratory into the clinic.

Together with Dr. Bart Janssen and his colleagues from the Institute of Human Genetics at the University of Heidelberg, he and his colleagues succeed in mapping the CNDP1 gene on chromosome 18, which is responsible for the formation of the enzyme carnosinase, and find evidence for the assumption of a hereditary diabetic nephropathy.

The number and combination of amino acids in the CNDP1 gene affects how much carnosinase is released. Studies on patients show that there are three different variants of this gene. In the variant with the longest sequence of DNA bases, much of the enzyme carnosinase is produced and released. This enzyme breaks down the mini-protein carnosine. However, according to the results of experiments with kidney cells, a high level of carnosine in the blood protects against the harmful effects of high glucose levels and thus prevents kidney cell damage.

The shortest gene variant, the CNDP1 Mannheim variant, also known as  Mannheim gene, has the lowest enzyme production with only 2185 bases. A clinical study led by Prof. van der Woude shows that diabetics without kidney disease predominantly have the Mannheim gene. In them, a comparatively high proportion of kidney-protecting carnosine is measured in the blood. The longer gene variant, on the other hand, is mainly found in patients with diabetic nephropathy. These research results will be published in the August 2005 issue of "Diabetes," an internationally important journal for diabetes research.

His enthusiasm for science, his  thorough observation and his self-discipline lead to an impressive amount of research and more than 300 scientific publications. Prof. van der Woude is an internationally sought-after expert.

Prof. van der Woude also earned great merits as a university lecturer. In 2001, he became deputy dean for medical education at the Mannheim faculty and supervised a large number of final theses as well as post-doctoral theses. His students and doctoral candidates benefit from his great interest in their education and his interdisciplinary approach. Following the example of Groningen, he founded the "Junior Scientific Masterclass" program in Mannheim in 2002 with the aim of integrating scientific principles of medicine more strongly into the clinical part of the course. It continues today under the name "Fokko van der Woude-Kolleg".

The clinical care of patients, the quality of the teaching program and the scientific research attract international attention and make Mannheim a leader in German nephrology.

At the age of only 53, Prof. van der Woude passed away on December 4, 2006, after a long, serious illness. "He combined his extensive knowledge and strong sense of responsibility with a very high level of commitment both in the daily clinical routine and in research and teaching. In doing so, he earned an extraordinarily high reputation far beyond the region and beyond professional circles," the Mannheim Hospital pays tribute to Prof. Fokko van der Woude.

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