2010

Post-Doctoral Fellowships

	Dr. Moumita Barua, M.D. Beth Israel Deaconess Medical Center/Harvard Medical School Supervisor: Dr. Martin Pollak KRESCENT FELLOWSHIP 2010-2013 Dr. Moumita Barua will pursue her post-doctoral fellowship under the supervision of Dr. Martin Pollak at the Beth Israel Deaconess Medical Center in Boston. Dr. Barua is interested in focal and segmental glomerulosclerosis (shortened to FSGS), a disease that attacks the kidney's filtering system (glomeruli) and can lead to kidney failure. Studies of families with FSGS have revealed several disease-causing genes. Dr. Barua will study the contribution of these known disease-causing genes in a group of people with FSGS, both with and without a family history of the disease. She also hopes to discover new FSGS-causing genes. The project is intended to increase our understanding of the genetic basis of FSGS. This is the first step in understanding the processes that malfunction in the kidney in FSGS, with the eventual goal of designing effective targeted therapies.
	Dr. Mathieu Lemaire, M.D. Yale School of Medicine, Howard Hughes Medical Institute Supervisor: Dr. Richard P. Lifton KRESCENT FELLOWSHIP 2010-2013 Mathieu Lemaire is currently pursuing a PhD at Yale in the laboratory of Dr. Richard Lifton (Investigative Medicine Program). He received his M.D. from McGill in 2004 and completed his Pediatric Nephrology training at Sick Kids (Toronto) in 2009. His project will focus on Dent’s disease: a genetic disease of the proximal tubule. The proximal tubule is one of the most important parts of the kidney filtration system as it plays a key role in reabsorbing vital components such as sodium and other ions, water, glucose, and amino acids back into the blood. When the proximal tubule is unable to this, patients become very sick because the body is unable to retain these vital elements. Unfortunately, genetic diseases of the proximal tubule are severe and never go away. Presently, there are two genes identified in the development of Dent’s disease. However, there is a large group of people who have a disease that looks exactly like Dent’s disease but who do not have a mutation of these two genes. This means that there are very likely other genes involved in Dent’s disease. Dr. Lifton’s laboratory has established an international network to study Dent’s disease. Dr. Lemaire will use cutting-edge genomic technology known has whole exome capture to make a snapshot of nearly all the human genes at once to identify the genes involved in Dent’s disease. This project will be the first time that this technology will be used on a large group of patients that are not related to each other. Finding novel disease-causing genes for Dent’s Disease will have important diagnostic implications for these patients and may suggest new therapies as well as furthering our general understanding of proximal tubule function.
	Dr. Annie Moisan Massachusetts General Hospital Cancer Centre, Harvard Medical School Supervisor: Dr. Nabeel Bardeesy KRESCENT FELLOWSHIP 2010-2013 Dr. Annie Moisan will complete her Post-Doctoral Fellowship under the supervision of Dr. Nabeel Bardeesy at Massachusetts General Hospital Cancer Centre/Harvard Medical School where she will study how disturbances in regenerative cells lead to cancer development. Many cancers appear to arise in damaged regenerative cells that continually reproduce themselves in an unregulated manner and lose their ability to convert into mature, non-dividing cells. The pediatric kidney cancer, Wilms' tumor, provides a good model to investigate how disturbances in cells lead to cancer development. Wilms' tumors arise from kidney cells that have a compromised ability to undergo normal differentiation. Her team recently identified mutations in a new gene, WTX, in 30% of cases of Wilms' tumor. Their findings predict that WTX is critical in controlling how kidney cells decide whether to differentiate or to regenerate, and suggest that mutations in WTX may increase the number of cells at risk for becoming cancer cells. Her proposed research aims at defining exactly how WTX controls cells and at how loss of cell regeneration control leads to cancer development. This work should point to new strategies for developing drugs to prevent and treat cancers that have WTX mutations and thereby increase the quality of life of Canadian patients. In addition, understanding the role of WTX in stem cells throughout the body could lead to valuable insights for regenerative medicine aimed at repairing damaged tissues.

New Investigator Awards

	Dr. David Cherney, M.D. Toronto General Hospital CDA-KRESCENT NEW INVESTIGATOR AWARD 2010-2013 Dr. David Cherney is a new investigator at the University of Toronto. He obtained his MD from McGill University. He completed his Post-Doctoral Fellowship, funded by the KRESCENT Program, with Dr. Judy Miller at the Toronto General Hospital. The aim of Dr. Cherney’s work is to understand how diabetes affects kidney and blood vessel function. Diabetes mellitus (DM), the leading cause of kidney failure, damages blood vessels. The factors that cause kidney and artery injury in DM include high blood sugars and stimulation of the renin angiotensin system (RAS). Activation of this hormone system leads to inflammation in both the kidney and blood vessels. Although the RAS can be blocked with medications such as angiotensin converting enzyme inhibitors (ACEi) and ‘direct rennin inhibitors” (DRI) the effect of these medications, alone and in combination, on blood vessel function and on proteins that mediate kidney injury is unknown. The findings are expected to lead to new approaches to the management of diabetes mellitus.
	Dr. Emmanuelle Cordat University of Alberta AMGEN-KRESCENT Joint New Investigator Award 2010 – 2013 KRESCENT INFRASTRUCTURE SUPPORT 2010-2011 Dr. Emmanuelle Cordat is a new investigator at the University of Alberta. She obtained her MSc and PhD degrees from the Université Nice Sophia Antipolis (France) and in 2007 completed a post-doctoral training with Dr. Reinhart Reithmeier at the University of Toronto. Dr. Cordat’s research focuses on understanding distal renal tubular acidosis and preventing kidney stone formation. The kidney is the body’s filter that ensures all waste products are eliminated, while retaining vital components. One vital molecule is bicarbonate, which must be retained to compensate for the acid produced while processing food. Inside our kidney, a specialized protein, the anion exchanger 1 (AE1) ensures that bicarbonate is pumped back into the blood. Some individuals are unable to properly retain bicarbonate because their AE1 bicarbonate pump is not working properly due to inherited mutations, thus bicarbonate is eliminated in urine instead of being retained. As a result, those affected may produce kidney stones, may have difficulty to thrive, and may develop bone disease. For several years, her research has focused on this disease, and great progress has been made to understand how it develops. She uses kidney cells to express these altered AE1 pumps and studies what about them is not working properly. Once her team has a good understanding of why this malfunctioning pump is inducing the disease, they will be able to look for tools to prevent it from developing.
	Dr. Sunny Hartwig University of Prince Edward Island KRESCENT NEW INVESTIGATOR AWARD 2010-2013 KRESCENT INFRASTRUCTURE SUPPORT 2010-2011 Dr. Sunny Hartwig is a new investigator at the University of Prince Edward Island. She obtained her Ph.D. from the University of Toronto and completed her Post-Doctoral Fellowship with Dr. Jordan Kreidberg at the Children’s Hospital Boston, Harvard University. Congenital human kidney diseases , Frasier Syndrome, Denys Drash Syndrom, are characterized by severe renal dysplasia (a tubular malformation of the kidney) and are linked to mutations of the Wilm’s Tumour Suppressor-1 (WT-1) gen. WT-1 gene mutations are also linked to the development of Wilm’s Tumour (the most common solid tumour in children). In her research, Dr. Hartwig, will study the role of SoxC genes in early kidney development and how these genes are regulated by WT-1. Sox genes are critical in the development genes that have been shown to coordinate cell specification and differentiation in non-renal tissue. Their role in the developing kidneys has not been determined nor has their function in the kidney. Dr. Hartwig’s study will define the critical role of the Sox and WT1 genes in early kidney development and will provide new insights in the development of Wilm’s Tumour, and lay the foundation for new therapeutic strategies that will treat, reverse and ultimately prevent kidney disease in these children.
	Dr. Jean-Philippe Lafrance, M.D. Maisonneuve-Rosemont Hospital Research Centre FRSQ (MSSS)-KRESCENT Joint New Investigator Award 2010 – 2013 KRESCENT INFRASTRUCTURE SUPPORT 2010- 2011 Dr. Jean-Philippe Lafrance is a new investigator at the Hôpital Maisonneuve-Rosemont Research Centre. He obtained his M.D. from the University of Montreal and also has a Masters in Epidemiology from McGill. More recently he completed his post-doctorate fellowship (funded by the KRESCENT Program) in pharmacoepidemiology under the supervision of Donald Miller at Boston University. Dr. Lafrance will study the incidence and risk factors of infection-related hospitalizations in patient receiving dialysis. Infections are the second leading cause of mortality, after cardiovascular disease, in patients receiving dialysis. Hospitalizations caused by an infection are highly frequent in patients undergoing dialysis treatments and may be followed by high risk of complications or death. Dr. Lafrance’s research aims to link information already collected in different provincial or national registries in order to evaluate the medical complications in patients undergoing dialysis. More precisely, he wants to establish the frequency of hospitalizations caused by infection and who (and why) is more susceptible to be hospitalized for that reason. Monitoring complications and mortality in dialysis patients is essential for administrators and other decision makers to plan resource allocation and to develop prevention strategies. These strategies will potentially reduce the burden of dialysis for the patients and for the health care system.

Allied Health Doctoral Award

Caren Rose
University of British Columbia
Supervisors: Drs. Charlyn Black and John S. Gill

KRESCENT ALLIED HEALTH DOCTORAL AWARD 2010-2013

Caren Rose holds a masters degree in statistics from Dalhousie, and is currently enrolled in a PhD in Health Services Research at the University of British Columbia, under the supervision of Drs. Gill and Black. She has spent the past 6 years working as a biostatistician in the field of kidney transplantation. Kidney failure patients can be treated with dialysis or transplantation. Compared to dialysis treated patients, transplant recipients live longer, have a higher quality of life and utilize fewer health care resources. Unfortunately, the supply of kidneys for transplantation does not meet the need for this treatment. Although living kidney donation is part of the solution, deceased donors remain the primary source of transplantable kidneys. Despite a strong willingness among Canadians to donate their organs, there has been no increase in deceased organ donation in Canada over the last decade. To understand the disparity between the apparent intention to donate and the actual act of donation, accurate measures of deceased organ donation activity are needed. The proposed work will apply a unique statistical method to administrative data that is currently collected in all Canadian hospitals to estimate the number of individuals eligible for deceased donation, in order to calculate the donor conversion rate (i.e. proportion of actual organ donors among eligible organ donors who die in hospital). Accurately ascertaining the potential for deceased organ donation and the observed conversion rates will inform strategies to increase deceased organ donation, ultimately improving the lives of patients with kidney failure.

The KRESCENT Program is a Strategic Training Program developed and supported by:

With additional generous support from:

AMGEN Baxter Corporation Merck-Frosst Canada Ltd. Ortho Biotech RocheShire BioChem Inc.