N.D. Rosenblum, M.D.
|Address:||Division of Nephrology |
The Hospital for Sick Children
555 University Avenue
Toronto, Ontario M5G 1X8
ACADEMIC STATUSDepartmental Status: Full Professor, Cross-Appointed.
Primary/Cross-appointments: Primary: Paediatrics.
Degrees: M.D. 1980
RESEARCHResearch Divisions: Reproduction and Development Platform
Research Interests: Definition of cellular and molecular mechanisms which control formation of the mammalian kidney with a specific focus on the morphogenesis of the renal collecting system. Growth factor signaling during morphogenesis of the kidney and the cerebellum.
Keywords: Renal development , branching morphogenesis, bone morphogenetic proteins, renal dysplasia, sonic hedgehog, beta-catenin, cerebellum.
The kidney is a paradigm for understanding the molecular control of embryonic mesenchymal-epithelial tissue interactions and how growth factor-dependent signaling controls mammalian organogenesis. Maldevelopment of the embryonic kidney and urinary tract is the major cause of childhood renal failure. Despite the importance of kidney and urinary tract development to health and disease, the underlying molecular mechanisms are largely unknown.
The kidney arises via reciprocal inductive interactions between a mesenchymal tissue, the metanephric blastema, and an epithelial tube, the ureteric bud. The blastema is induced to form nephrons, which consist of the glomerulus and the tubules proximal to the collecting ducts. The ureteric bud is induced to grow and branch, a process termed branching morphogenesis, and give rise to all the components of the collecting system including the collecting ducts, calyces, pelvis and ureter. Formation of a critical number of nephrons is required for normal kidney function and is dependent on both metanephric development and branching morphogenesis.
The major focus of research in my lab is to define mechanisms by which secreted growth factors and their cognate receptors control growth and branching of ureteric and collecting duct tubules, formation of a contractile ureter, and generation of nephrons from metanephric cells. We study these mechanisms using mouse collecting duct cells which can be induced to form tubules in three dimensional cultures in vitro, metanephric cells, cultured mouse embryonic kidney explants, transgenic mice and 'knock-out' mice.
We are investigating the actions of three major signaling pathways activated by Bone Morphogenetic Proteins (BMP), Sonic Hedgehog (SHH) and WNTs, respectively, primarily during kidney development and also during cerebellar morphogenesis. Our work in the embryonic kidney demonstrates that WNTs, HHs and BMPs play multifunctional roles to control morphogenesis of metanephric mesenchyme- and ureteric-derived tissues. In the cerebellum, signaling via HH effectors controls mid-hindbrain patterning, cell differentiation and tissue patterning. We are futher defining these actions at the level of cell-cell interactions, signaling mechanisms and transcription of genes that are essential during kidney and cerebellar development.
METHODS USEDCell and tissue culture: Neurons
Procedures: Gene expression analysis, immunohistochemistry, immunocytochemistry, microarrays, qRT-PCR, RT-PCR, signal transduction characterization, siRNA, western blot.
EQUIPMENT USEDAnalytical balances, benchtop centrifuge, blotting apparatus, culture hood, culture incubators, deconvolution fluorescence microscope, dissecting microscope, fluorescence microscope, gel apparatus, low and ultralow freezers, microwave oven, ProBlot hybridization oven, water baths.
SAMPLE PUBLICATIONS AND ABSTRACTS:Click on link to PubMed
PRESENT TRAINEESWeiqian Chen
PRESENT COLLABORATIONSWithin the Department of Physiology:
Outside the Department of Physiology:
Chi-chung Hui, Molecular Genetics, University of Toronto
York Pei , IMS, University of Toronto
Mark Henkelman, Department of Medical Biophysics, University of Toronto
Branden Wainwright, Department of Molecular Bioscience, University of Queensland
Roy Zent, Department of Medicine, Vanderbilt University
Steve Potter, Department of Developmental Biology, University of Cincinnati
Committee member/Officer of national or international scientific organization:
Canadian Society for Clinical Investigation
EUREKA Institute for Translational Medicine
Royal College of Physicians and Surgeons of Canada Clinical Investigator Program
Pediatric Scientist Development Program
Canadian Child Health Clinician Scientist Program
Society for Pediatric Research