Safe the date: 11th primary hyperoxaluria workshop, 27.6.-28.6.2014, Chicago, IL, USA




Chris Danpure, BSc, PhD

Christopher J. Danpure is Professor of Molecular Cell Biology in the Department of Cell and Developmental Biology and Division of Biosciences at University College London. By training, he is a biochemist, but in the last twenty years his research has covered the areas of clinical enzymology, clinical genetics, molecular biology, cell biology, molecular evolution, population genetics and structural biology. In 1986, his lab discovered that the basic enzyme defect in type 1 of the hereditary calcium oxalate (CaOx) kidney stone disease primary hyperoxaluria (PH1), the deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase (AGT). His team and co-workers were responsible for the rapid translation of these findings into the clinical management of the disease. Prof. Danpure carried out the first enzyme diagnosis for PH1 in 1986 as well as the first prenatal diagnosis in 1988. In addition, his lab was involved in the first use of enzyme replacement therapy in PH1 by liver transplantation in 1986.

In collaboration with colleagues from Japan, his lab was the first to clone the human AGT gene in 1990, following which his lab identified the first mutations and clinically-relevant polymorphisms. This work provided the foundation for all of the DNA-based postnatal and prenatal diagnostic procedures currently being used for PH1.

In 1989, Prof. Danpure showed that PH1 is caused by an unparalleled protein trafficking defect in a large subset patients. Here, AGT, which is normally peroxisomal in human liver cells, is mistargeted to the mitochondria. His lab's work on the molecular, cellular and structural bases of AGT mistargeting during the 1990s provided unique insights into the very different requirements of the peroxisomal and mitochondrial protein import machineries. In parallel with this human-orientated work, Prof. Danpure’s lab has also made major contributions to the understanding of the evolution of AGT targeting in other mammals. His work in this area over a number of years has provided one of the most remarkable examples of molecular adaptation to positive dietary selection pressure.

In 2003 Prof. Danpure’s lab solved the crystal structure of human AGT. This has not only provided rational explanations for how many of the mutations and polymorphisms in the AGXT gene affect the properties of AGT, but also allows the rational design of small molecules that might be able to counter these untoward effects by stabilising the AGT dimer. Such agents have enormous potential for the treatment of, not only PH1, but also possibly the much more common idiopathic CaOx stone diseases. In the latter context, Prof. Danpure’s lab has carried out investigations into the population genetics of AGXT polymorphisms and to what extent it determines susceptibility to idiopathic CaOx kidney stone disease, especially in relationship to dietary lifestyles.

In recognition of his contributions to the understanding of the molecular basis of hereditary kidney stone disease and for translating this understanding into its clinical management, Prof. Danpure was elected to the Fellowship of the Academy of Medical Sciences in 2001.

Ernst P. Leumann, MD

Prof. Dr. Ernst Leumann received his medical degree in 1961 at the University of Zürich, Switzerland, followed by a doctoral thesis on the vasopressin test in pediatrics under Prof. Andrea Prader. His training to specialize in Pediatric Nephrology started early after his first years as a physician, when he received teaching at different well known locations: 1966-67 Hôpital des Enfants Malades, Paris (Prof. P. Royer, Dr. R. Habib) 1967-68 New York Hospital, Cornell University, New York (Prof. W.W. McCrory) 1968-69 University of California, San Francisco (Prof. M.A. Holliday).

Thereafter, he came back to work again at the “Kinderspital”, the University Children’s Hospital in Zurich, first as senior registrar building up a dialysis facility for children and later (since 1982) as Head of the Pediatric Nephrology unit.

In 1978 he published his first paper regarding primary hyperoxaluria (Niederwieser A, Matasovic A, Leumann EP: Glycolic acid in urine. A colorimetric method with values in normal adult controls and in patients with primary hyperoxaluria. Clin Chim Acta 89, 13-23) and since, he was not only specifically involved in care taking of patients with primary hyperoxaluria, but also in basic and clinical research about this rare disease. He built up a large outpatient clinic for patients with primary hyperoxaluria, who received the whole range of therapy from conservative treatment up to combined liver-kidney transplantation at his institution. Very soon, at least all pediatric patients from Switzerland were seen in Zurich.

Next to his ongoing clinical duties in Switzerland he started to build-up a long-term program for (pediatric) kidney patients in Yerevan, Armenia, following an emergency relief operation after the earthquake in 1988. Even after his retirement in 2000 he still supported the partnership program with the Arabkir hospital in Yerevan, but he was also frequently involved in teaching, clinical or research support in countries with limited resources.

Prof. Leumann organized the 5th International Workshop on Primary Hyperoxaluria, which was held in an old monastery in Kappel/Zurich, on March 12/13, 1999. He had published 143 papers, a significant amount of them dealing with primary hyperoxaluria. He served as secretary General of the European Society for Pediatric Nephrology (ESPN, 1984-89) and is its honorary Member since 2000. He also is Honorary member of the International Pediatric Nephrology Association (IPNA, 2001), as well as of the Polish Society (2006) and of the German Society for Pediatric Nephrology (2008).