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Rosenblum Lab

Brief Biography

Dr. Rosenblum is a clinician scientist trained in Paediatric Nephrology and experimental nephrology. Since joining the Hospital for Sick Children and University of Toronto in 1993, Norman has established a research program in kidney development within the Program in Developmental and Stem Cell Biology at SickKids and the University of Toronto Collaborative Program in Developmental Biology. His research is focused on genetic and molecular mechanisms that control normal and disrupted mammalian renal development and clinical outcomes in affected humans.  Support for this work is provided via grants from the Kidney Foundation of Canada, the Canadian Institutes of Health Research and the Canada Research Chairs program.

Dr. Rosenblum has a major interest in the education and career development of clinician scientists at an individual and programmatic level. As Associate Dean, Physician Scientist Training in the Faculty of Medicine, Norman directs the MD-PhD program, the Royal College of Physicians and Surgeons Clinician Investigator Program and serves as Associate Director (Education) of the McLaughlin Centre for Molecular Medicine. Dr. Rosenblum played a leading role in the founding of the Canadian Child Health Clinician Scientist Program (CCHCSP), an interdisciplinary training program aimed at generating the next generation of Clinician-Scientists in the field of child health in Canada, and has acted as Principal Investigator of the CCHCSP since its inception

Research Interests

• kidney development\
• branching morphogenesis
• growth factor signalling
• renal dysplasia
• congenital kidney disorders

Research Activities

The major focus of Dr. Rosenblum’s laboratory research is molecular and cellular mechanisms that control renal development in humans and mice, a model of human renal development. His laboratory is investigating the functions of signaling pathways controlled by Bone Morphogenetic Proteins, Sonic Hedgehog and WNT proteins during normal kidney formation and in renal malformation. Work resulting from these endeavors has demonstrated distinct functions for these effectors in controlling renal branching morphogenesis and nephron formation. Further, Dr. Rosenblum’s work invokes increased expression of beta-catenin, the central effector in the canonical WNT pathway, in the pathogenesis of renal dysplasia. Dr. Rosenblum leads a North American six-centre study aimed at identifying genetic defects in human renal malformation. A relatively recently developed theme in the Rosenblum Lab, arising from genetic mouse models developed to interrogate the Hedgehog signaling pathway, is focused on the formation of the cerebellum.

Future Research Interests

Our ongoing research is directed at defiing how BMPs, SHH, and beta-catenin control kidney development and determining how 'cross-talk' between BMP signaling effectors and beta-catenin cause renal maldevelopment and cyst formation.

Achievements

• Member, Editorial Board, Journal of the American Society of Nephrology, 2005 - present.
• Aventis Pasteur Research Award, Canadian Paediatric Society, 2004
• New Member Outstanding Science Award, American Pediatric Society, 2006
•  New Member Outstanding Science Award, American Pediatrics Society, 2006
•  Paediatric Academic Leadership-Clinical Investigator Award, Paediatric Chairs of Canada, 2009

Publications

Cain, JE, Islam E, Haxho F, Chen L, Bridgewater D, Nieuwenhuis E, Hui C-C, Rosenblum ND. GLI3 repressor controls nephron number via regulation of Wnt11 and Ret in Ureteric Tip Cells.PLoS ONE 4(10): e7313. doi:10.1371/journal.pone.0007313, 2009.  

Hartwig S, Bridgewater D, Cain J, DiGiovanni V, Mishina Y, Rosenblum ND.  The BMP receptor ALK3 controls collecting system formation during murine kidney development. J AmSoc Neph 19:117-124, 2008.

Bridgewater D, Cox B, Cain J, Lau A, Althaide V, Gill P, Kuure S, Sainio K, Rosenblum ND. Canonical WNT/b-catenin signaling is required for ureteric branching. Developmental Biology 317:83-94, 2008.

Gill PS, Rosenblum ND. Control of murine kidney development by Sonic Hedgehog and its GLI effectors. Cell Cycle, 5:13, 1426-1430, 2006

Hu MC, Mo R, Bhella S, Wilson CW, Chuang P-T, Hui C-C, Rosenblum ND. GLI3-dependent transcriptional repression of Gli1 and Gli2 and kidney patterning genes disrupts renal morphogenesis. Development 133:569-578, 2006.

Mill P, Mo, R, Hu MC, Dagnino L, Rosenblum ND, Hui C-C. Transcriptional and post-translational proliferative control by SHH-dependent GLI activator and repressor functions in the embryonic epidermis. Developmental Cell 9: 293-303, 2005.

Hartwig S, Hu MC, Cella C, Piscione TD, Filmus J, Rosenblum ND. Glypican-3 Modulates Inhibitory Bmp2-Smad Signaling to Control Renal Development in vivo. Mechanisms of Development 122: 928-938, 2005.

Leung-Hagestejn C, Hu MC, Mahendra AS, Hartwig S, Klamut H, Rosenblum ND, Hannigan GE. Integrin linked kinase mediates BMP7 dependent renal epithelial cell morphogenesis. Molecular and Cellular Biology 25: 3648-3657, 2005.

Hu MC, Rosenblum ND. Smad1, beta-catenin and TCF4 associate in a molecular complex with the c-MYC promoter in dysplastic renal tissue and cooperate to control c-MYC transcription. Development 132:215-225, 2005.

Karihaloo A, Kale S, Rosenblum ND, Cantley L. HGF mediated renal epithelial branching morphogenesis is regulated by Glypican-4 expression. Molecular and Cellular Biology 24:8745-8752, 2004.

Hu MC, Hartwig S, Wasserman D, Rosenblum ND. p38MAPK Acts in the BMP7-dependent stimulatory pathway during epithelial cell morphogenesis and is regulated by Smad1. J Biological Chemistry. 279: 12051-12059, 2004.

Hu MC, Rosenblum ND. Genetic regulation of branching morphogenesis: lessons learned from loss-of-function phenotypes. Pediatric Research 54: 433-438, 2003.

Hu MC, Piscione TD, Rosenblum ND. Elevated Smad1/beta-catenin molecular complexes and renal medullary dysplasia in ALK3 transgenic mice. Development 130:2753-2766, 2003.