Norman Rosenblum

Staff Nephrologist and Senior Scientist, The Hospital for Sick Children
Professor of Paediatrics, Physiology, and Laboratory Medicine and Pathobiology,
Scientific Director - CIHR Institute of Nutrition, Metabolism and Diabetes

Research Synopsis

Keywords: Renal development, branching morphogenesis, transforming growth factor proteins,  renal dysplasia, sonic hedgehog, organoids

Detailed Description: 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 branching morphogenesis, formation of a contractile ureter, and generation of nephrons. We study these mechanisms using primary kidney cell cultures, tissue explants, kidney organoids, transgenic mice and 'knock-out' mice.

We are investigating the actions of three major signaling pathways activated by Transforming Growth Factor Beta (TGFB), Sonic Hedgehog (SHH) and Integrin-linked kinase (ILK) respectively, primarily during kidney development. Our work in the embryonic kidney demonstrates that HH, TGFB and ILK play multifunctional roles to control morphogenesis of metanephric mesenchyme- and ureteric-derived tissues. We are futher defining these actions at the level of cell-cell interactions, signaling mechanisms and transcription of genes that are essential during kidney development.
 

METHODS USED

Cell and tissue culture: iMCD cells, kideny organoids, iPSCs, embryonic kidney explants

Procedures: RNA Sequencing, Single-cell RNA Sequencing, Gene expression analysis, immunohistochemistry, immunofluorescence, microarrays, qRT-PCR, signal transduction characterization, siRNA, western blot

EQUIPMENT USED

Epifluorescence, Confocal and Lightsheet microscopy, Tissue Culture Hood, ViiA7 Quantitiative RT-PCR machine, Dissecting light microscopes, Analytical balances, Wester Blotting apparatus, Centrifuges.

PRESENT TRAINEES

Yilin Tian
Robert D'Cruz
Xiangyue Hu

PRESENT COLLABORATIONS

Within the Department of Physiology:
Ian Rogers

Outside the Department of Physiology:
James Ellis, Department of Molecular Genetics, U Toronto
Nina Knoers, UMC Utrecht, Utrecht
Kirsten Renkema, UMC Utrecth, U Utrecht

Committee member/officer of national/international scientific organizations
List:
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
American Pediatric Society
Canadian Society of Nephrology

PRESENT GRANT COMMITTEES SERVED ON
Agency: CIHR
Committee: Hematology, Digestive Disease, Kidney Operating Grants Committee

Agency: Alberta Innovates
Committee: Health Professional Fellowship Committee

Recent Publications

Lab Website: https://lab.research.sickkids.ca/rosenblum/publications/

Appointments