Research Awards Recipients

Chronic kidney disease greatly affects the health of the general population. Nephronophthisis is the most frequently inherited cause of chronic kidney disease in children and the young. The term nephronophthisis refers to the wasting away (from Greek, phthisis) of the smallest unit of the kidney, the nephron. Affected children are typically born to unaffected parents and clinical symptoms, such as increased thirst or urination, are often mild and may go unnoticed. When the child or young adult finally comes to their doctor’s attention, the kidney damage cannot be undone. Once kidney function is lost, the treatment options are either hemodialysis (which filters toxins out of the blood) or kidney transplant. Both options are associated with significant health risks and are very labour and cost intensive. This highlights the need for early identification of at-risk individuals and the need for the development of new treatment options. Inherited changes in a number of genes are known to cause nephronophthisis. Dr. Friedhelm Hildebrandt at the Boston Children’s Hospital is a world leader at identifying new genes which cause kidney disease when changed. The goal of this project in his laboratory is firstly, to better understand the role of a recently identified kidney-disease gene discovered in a family from Montreal. We will use Dr. Hildebrandt’s database of >1,500 families with unsolved cases of kidney disease to screen for other families with changes in this gene. To do this, we will use state-of-the-art technology, such as whole-exome capture and next-generation sequencing. Both methods allow us to look at a vast number of genes in an efficient manner. We will then use well-known animal models of nephronophthisis, such as zebrafish, to further detail how this gene causes kidney disease and use these animal models to screen for new therapies. This work will hopefully lead to the development of new treatment options for genetic forms of kidney disease.

Biography
Dr. Thomas Kitzler will complete his research fellowship under the supervision of Dr. Friedhelm Hildebrandt at Boston Children’s Hospital – Harvard Medical School. His project focuses on the discovery and characterization of novel kidney disease genes by means of whole-exome sequencing and zebrafish animal models. These models will then be used to screen for novel targeted therapies. Dr. Kitzler completed his medical residency at the department of Medical Genetics at McGill University where he was also involved in basic research in the field of Nephrology. Dr. Kitzler obtained his degree at the Medical University of Graz, Austria.

Chronic kidney disease (CKD) is associated with significant morbidity and mortality. In the US alone, 26 million individuals have CKD and millions of others are at risk. Nephronophthisis (NPHP) is an autosomal-recessive cystic kidney disease and it is the most frequent genetic cause of CKD in the first three decades of life. In recent years, it has been demonstrated that NPHP shows a high degree of genetic heterogeneity. Elucidating the underlying genetic and molecular pathomechanisms of hereditary kidney disease is paramount for identifying at-risk individuals and for the development of novel targeted therapies to alter or hopefully even reverse disease progression.

Dr. Kitzler will characterize novel NPHP candidate genes. He will then use zebrafish models to screen for novel targeted therapies for genetic causes of kidney disease, for which currently no treatment exists.