null Paul Goodyer, MD
Nephrology • pediatrics • hereditary renal disease • kidney development • developmental biology • growth factors • PAX2 • Wnt • apoptosis • polycystic kidney • renal hypoplasia
My research focuses on unraveling the molecular basis for orphan diseases of the kidney and translating the information into new therapies. It is closely tied to patients' needs in the Renal-Genetics Clinic at the Montreal Children's Hospital. We have discovered dysfunctional variants of three genes that set congenital nephron number during fetal life. With colleagues in India, we are studying whether maternal vitamin A deficiency accounts for renal hypoplasia. We are developing a cell-based therapy for cystinosis, a rare genetic disease that accounts for about one third of pediatric renal transplants in Quebec. Our strategies include isolating cells from our patients, correcting the genetic mutations in the cultured cells and testing whether the cells can re-integrate into the cystinotic kidney. Our group has also found that a non-canonical Wnt signalling pathway drives cyst formation during kidney development in children with polycystic kidney disease. We are now studying whether cyst formation can be reversed by augmenting the non-canonical WNT signalling pathway.
Iglesias DM, El-Kares R, Taranta A, Bellomo F, Emma F, Besouw M, Levtchenko E, Toelen J, van den Heuvel L, Chu L, Zhao J, Young YK, Eliopoulos N, Goodyer P. Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro. PLoS One 7(8):e42840, 2012.
Miller MM, Iglesias DM, Zhang Z, Corsini R, Chu LL, Murawski I, Gupta I, Somlo S, Germino GG and Goodyer PR. T-Cell Factor/&beta-Catenin Activity is Suppressed Normally in Two Independent Models of Autosomal Dominant Polycystic Kidney Disease. Kidney Int. 80(2):146-53, 2011 Jul. doi: 10.1038/ki.2011.56. Epub 2011 Mar 9.
Zhang Z, Pascuet E, Hueber P-A, Chu LL, Bichet DG and Goodyer P. Targeted inactivation of EGF receptor inhibits renal collecting duct development and renal concentrating ability in adult mice. J Am Soc Nephrol. 2010 Feb 4.
Zhang Z, Iglesias D, Eliopoulos N, El-Kares R, Chu LL, Romagnani P and Goodyer P. A variant OSR1 allele which disturbs OSR1 mRNA expression in renal progenitor cells is associated with reduction of newborn kidney size and function. Hum Mol Genetics ;20(21):4167-74, 2011 Nov 1. Epub 2011 Aug 5.
Wu MK, Sabbaghian N, Xu B, Addidou-Kalucki S, Bernard C, Zou D, Reeve AE, Eccles MR, Cole C, Choong CS, Charles A, Tan TY, Iglesias DM, Goodyer PR, Foulkes WD. Biallelic DICER1 mutations occur in Wilms tumours. J Pathol. 230(2):154-64, 2013 Jun.