Senior Scientist, Chronic Disease Program
Ottawa Hospital Research Institute

Professor, Medicine / Cellular & Molecular Medicine
University of Ottawa

Dr. Kennedy’s research program has been funded by the Canadian Institutes for Health Research (CIHR), the Kidney Foundation of Canada (KFOC), and the Canada Foundation for Innovation. He was a CIHR New Investigator Scholar. He has held CIHR operating grants continuously since 2001, seeking to identify factors such as prostaglandins and reactive oxygen species responsible for mediating damage to cells within the kidney’s filtration barrier – known as podocytes. Such injury results in abnormal leakage of protein into the urine. Identifying the specific factors responsible for filtration barrier injury may reveal a novel therapeutic target for the prevention of glomerular diseases. Most recently, his work defined a critical role for a novel NADPH oxidase isoform (Nox5) in diabetic kidney disease. Dr. Kennedy’s KFOC-funded research has shed light on how mutations in the alpha-actinin-4 gene lead to an inherited form of a common kidney disease - focal segmental glomerulosclerosis (FSGS). This research project employs transgenic technology to reproduce this disease state in mice so that its progression can be better studied and novel therapies developed.

1. Robert L. Myette, Fengxia Xiao, Pavel Geier1, Janusz Feber1, Dylan Burger and Christopher R. J. Kennedy. Urinary podocyte-derived large extracellular vesicles are increased in paediatric idiopathic nephrotic syndrome. Nephrol Dial & Transplantation. 2023; 38, 2089-91.

2. Jha, J.C., Dai, A., Garzarella, J., Charlton, A., Urner, S., Østergaard, J.A., Okabe, J., Holterman, C.E., Skene, A., Power, D.A., Ekinci, E.I.,Coughlan, M.T., Schmidt, H. H.W., Cooper, M.E., Touyz, R.M., Kennedy, C.R.J., Jandeleit-Dahm, K. Independent of Renox, NOX5 Promotes Renal Inflammation and Fibrosis in Diabetes by Activating ROS-Sensitive Pathways. Diabetes 2022; 71, 1282–1298.

3. Holterman CE, Boisvert NC, Thibodeau JF, Kamto E, Novakovic M, Abdelrahman K, Ferguson S, Kennedy CRJ. Podocyte NADPH Oxidase 5 promotes renal inflammation regulated by the toll-like receptor pathway. Antioxid Redox Signal. 2019;30(15):1817-1830.

4. Holterman CE, Boisvert NC, Thibodeau J-F, Kamto E, Novakovic M, Abdelrahman K, Ferguson S, Kennedy CRJ. Podocyte NADPH Oxidase 5 promotes renal inflammation regulated by the toll-like receptor pathway. Antioxid Redox Signal. 2018;doi.org/10.1089/ars.2017.7402.

5. Boisvert NC, Holterman CE, Gutsol A, Coulombe J, Pan W, Alexander RT, Gray DA, Kennedy CRJ. Ubiquitin COOH-terminal hydrolase L1 deletion is associated with urinary α-klotho deficiency and perturbed phosphate homeostasis. Am J Physiol Physiol. 2018;315(2):f353-363.

6. Boisvert NC, Holterman CE, Thibodeau J-F, Nasrallah R, Kamto E, Comin CH, da F. Costa L, Carter A, Hébert RL, Gutsol A, Cron GO, Lacoste B, Gray DA, Kennedy CRJ. Hyperfiltration in Ubiquitin C-terminal hydrolase L1 -deleted mice. Clin Sci. 2018;132:1453-1470.

7. Boisvert NC, Holterman CE, Gutsol A, Coulombe J, Pan W, Alexander RT, Gray DA, Kennedy CRJ. Ubiquitin C-terminal hydrolase L1 deletion is associated with urinary α-klotho deficiency and perturbed phosphate homeostasis. Am J Physiol Physiol. 2018;315(2):F353-F363. http://www.ncbi.nlm.nih.gov/pubmed/29667913

8. Thibodeau JF, Holterman CE, He Y, Carter A, Cron GO, Boisvert NC, Abd-Elrahman KS, Hsu KJ, Ferguson SS, Kennedy CRJ. Vascular smooth muscle-specific EP4 receptor deletion in mice exacerbates angiotensin II-induced renal injury. Antioxid Redox Signal. 2016;25(12):642-656.

9. Burger D, Thibodeau JF, Holterman CE, Burns KD, Touyz RM, Kennedy CRJ. Urinary podocyte microparticles identify prealbuminuric diabetic glomerular injury. J Am Soc Nephrol. 2014;25(7): 1401-1407.

10. Holterman CE, Thibodeau JF, Towaij C, Gutsol A, Montezano AC, Parks RJ, Cooper ME, Touyz RM, Kennedy CRJ. Nephropathy and elevated BP in mice with podocyte-specific NADPH oxidase 5 expression. J Am Soc Nephrol. 2014;25(4):784-797.

11. Read NC, Gutsol A, Holterman CE, Carter A, Coulombe J, Gray DA, Kennedy CRJ. Ubiquitin C-terminal hydrolase L1 deletion ameliorates glomerular injury in mice with ACTN4-associated focal segmental glomerulosclerosis. Biochim Biophys Acta. 2014;1842(7):1028-1040.

12. Thibodeau JF, Holterman CE, Burger D, Read NC, Reudelhuber TL, Kennedy CRJ. A novel mouse model of advanced diabetic kidney disease. PLoS One. 2014;9(12):e113459.

13. Thibodeau JF, Nasrallah R, Carter A, He Y, Touyz RM, Hébert RL, Kennedy CRJ. PTGER1 Deletion Attenuates Renal Injury in Diabetic Mouse Models. Am J Pathol. 2013;183(6):1789-802.

14. Stitt-Cavanagh EM, Faour WH, Takami K, Carter A, Vanderhyden B, Guan Y, Schneider A, Breyer MD, Kennedy CRJ. A maladaptive role for EP4 receptors in podocytes. J Am Soc Nephrol. 2010; 21(10):1678-90.

Diabetes; Hypertension; Kidney disease