The Kidney Foundation of Canada

Dr Advani 

Dr. Andrew Advani

St. Michael's Hospital, Ontario

Epigenetics in focal segmental glomerulosclerosis

2017-2019:  $100,000  |  Biomedical Research Grants  |  Category: Kidney Biology


Dr. Andrew Advani is an Associate Profession/Clinician Scientist and Staff Endocrinologist at St. Michael's Hospital and the University of Toronto. He completed his medical degree at Edinburgh University (UK) in 1996 and his PhD at Newcastle University (UK) in 2003 and he was appointed as a Principal Investigator at St. Michael's Hospital in 2008. His clinical interests are focused on the care of young people with Type 1 diabetes. Dr. Advani's research program is concentrated on understanding the causes of the long-term complications of diabetes, particularly diabetic kidney disease. Within this field, his lab studies the ways that epigenetic processes contribute towards or protect against the development of kidney disease. Supported by the Kidney Foundation of Canada, Dr. Advani's lab is working to see how these epigenetic processes may also affect the development of non-diabetic kidney diseases, in particular, focal segmental glomerulosclerosis. Dr. Advani has a keen interest in the mentorship of postgraduate trainees who wish to develop research skills in diabetes and kidney disease. He has published over 60 peer-reviewed articles and he was the recipient of the 2015 Dr. Charles Hollenberg Young Investigator Award from the Canadian Society of Endocrinology and Metabolism. 

Lay Summary

Focal segmental glomerulosclerosis (FSGS) is a serious kidney disease. We urgently need new treatments. FSGS can have a number of different causes but, regardless of its causes, all forms of FSGS are associated with damage to particular cells in the kidney called podocytes. In our earlier work, we have discovered that the health of podocytes is maintained by a group of processes that go on in cells called "epigenetics". The term epigenetics refers to changes in the way genes carry the genetic code to make proteins that do not involve changes in the typical DNA code. For example, in order for each long DNA strand to be packed inside of a cell, it has to be tightly wrapped around spools of proteins called histones. If these spools are modified by chemical reactions this can affect how genes nearby make the proteins that they code for. We have discovered that taking away a particular chemical change from histone proteins (called demethylation) causes damage to podocytes and worsens FSGS. In this proposal, we will look to see whether blocking the enzymes that take away this chemical reaction (called demethylases) can be used as a treatment for FSGS. The experiments will be performed by treating podocytes grown in Petri dishes and mice with FSGS with a new experimental medication (called an inhibitor) that stops the demethylases from working. The studies will shed new light on how FSGS occurs, potentially paving the way for the development of a new treatment for FSGS.