Academic Background

1985 B.Sc. University of St. Michael’s College, Faculty of Arts and Science, University of Toronto, Toronto, ON

1987 M.Sc. Department of Physiology, School of Graduate Studies, University of Toronto, Toronto, ON

1991 M.D. Faculty of Medicine, Queen’s University, Kingston, ON

1991 LMCC Medical Council of Canaa

1992 Independent License, College of Physicians and Surgeons of Ontario

1994 FACP, American Board of Pediatrics

1995 FRCP(C), The Royal College of Physicians and Surgeons of Canada

2002 Ph.D. Institute of Medical Science, School of Graduate Studies, University of Toronto, Toronto, ON

Research Interests

• Kidney development
• Renal epithelial differentiation
• Glomerulogenesis

Dr. Piscione’s lab studies formation of nephrons, renal epithelial tubules which are the functional units of the mammalian kidney. Individual mature nephrons are comprised of distinct epithelial compartments, or segments, which collectively originate during kidney development from common epithelial progenitors. Defective progenitor differentiation affecting either total nephron formation or formation of the glomerular compartment exclusively, are thought to underlie two major causes of childhood chronic kidney disease – renal dysplasia and glomerulosclerosis, respectively. The primary goal of Piscione’s research, thus, is to determine molecular mechanisms that control nephron epithelial cell differentiation as a means to understand the cause of renal dysplasia and glomerulosclerosis. A major focus of this work involves examining the role of Notch signaling in this process since Notch is known to control cell differentiation in many developing organ systems.

Piscione’s analyses of individual Notch pathway member’s expression patterns in developing nephrons suggests a spatiotemporal condition for decreased Notch signaling during glomerular epithelial cell, or podocyte, terminal differentiation. Using a transgenic system that induces constitutive Notch activation in developing podocytes, Piscione’s lab subsequently revealed that sustained Notch signaling opposes podocyte terminal differentiation, and causes glomerulosclerosis in young mice. Current work involves identifying molecular targets of canonical Notch signaling in podocytes, which may function in pathologic mechanisms associated with nephrotic syndrome and progressive glomerulosclerosis.

Clinical Interests

External Funding

Last 5 Years

The role of Notch1 in kidney development, Kidney Foundation of Canada, 07/2004 Biomedical Grant,  $149,610 PI

Clinical genetic test development for focal segmental glomeruloscierosis, National Institutes of Health (NIH). 07/2007 $52,000 C

Norman Siegel Research Scholar Grant, The role of Notch signaling in focal segmental glomerulosclerosis. The American Society of Nephrology. 08/2007 $200,000 PI

Biomedical Grant, Notch signaling and control of podocyte cell proliferation in development and disease. Kidney Foundation of Canada. 07/2009 $100,00 PI

Achievements

Selected

2000 Merit Award Institute of Medical Science, School of Graduate Studies, University of Toronto, Toronto, ON

2000 Best Trainee Abstract Canadian Society of Nephrology.  The Canadian Society of Nephrology Annual Meeting, Montreal, QC.

2003 The Annual Ontario Gerry Francis Camp Award.   The Kidney Foundation of Canada.  In recognition of hard work, dedication, and outstanding commitment to Camp Dialysun.

2002 American Pediatric Society/Societies for Pediatric Research Young Investigators Travel Award American Pediatric Society/Societies for Pediatric Research.  Societies for Pediatric Research 2002 Annual Meeting, Baltimore, MD, May 3-7, 2002.

2004 International Pediatric Nephrology Association (IPNA) Junior Faculty Travel Award International Pediatric Nephrology Association (IPNA).  The Ninth International Workshop on Developmental Nephrology, Barossa Valley, South Australia, August 25-27, 2004.

2004 Biomedical Scholarship ($90,000 CDN) The Kidney Foundation of Canada

2007 Norman Siegel Research Scholar Award American Society of Nephrology

Publications

Selected

Piscione TD, Yager TD, Gupta IR, Grinfeld B, Pei Y, Attisano L, Wrana JL, and Rosenblum ND: BMP-2 and OP-1 exert direct and opposite effects on renal branching morphogenesis. Am J Physiol (Renal Physiol) 1997  273:F961-F975.  PA

Cano-Gauci DF, Song HH, Yang H, McKerlie C, Choo B, Shi W, Pullano R, Piscione TD, Grisaru S, Soon S, Sedlackova L, Tanswell AK, Mak TW, Yeger H, Lockwood GA, Rosenblum ND, Filmus J: Glypican-3-deficient mice exhibit developmental overgrowth and some of the abnormalities typical of Simpson-Golabi-Behmel syndrome.  J Cell Biol 1999  146:255-264.  Col

Gupta IR, Piscione TD, Grisaru S, Phan T, Macias-Silva M, Zhou X, Whiteside C, Wrana JL, Rosenblum ND: Protein kinase A is a negative regulator of renal branching morphogenesis and modulates inhibitory and stimulatory bone morphogenetic proteins.  J Biol Chem 1999  274:26305-14.  Col

Gupta IR, Macias-Silva M, Kim S, Zhou X, Piscione TD, Whiteside C, Wrana JL, and Rosenblum ND: BMP-2/ALK3 and HGF signal in parallel  to regulate renal collecting duct morphogenesis.  J Cell Sci 2000  113:269-278.  Col

Piscione TD, Phan T, and Rosenblum ND: BMP7 controls collecting tubule cell proliferation and apoptosis via Smad1-dependent and Smad1- independent pathways.  Am J Physiol (Renal Physiol)  2001  280:F19-F33.  PA

Hu MC, Piscione TD, Rosenblum ND: Elevated SMAD1/beta-catenin molecular complexes and renal medullary cystic dysplasia in ALK3 transgenic mice.  Development 2003 130:2753-2766.  Col

Piscione TD, Wu MYJ., and Quaggin SE: Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis.  Gene Expr Patt 2004  4:707-711.  SRA

Hartwig S, Hu MC, Cella C, Piscione T, Filmus J, and Rosenblum ND: Glypican-3 Modulates Inhibitory Bmp2-Smad Signaling to Control Renal Development in vivo.  Mech Dev 2005  122(7-8):928-938.  Col

Waters AM, Wu MYJ, Onay T, Scutaru J, Liu J, Lobe CG, Quaggin SE, and Piscione TD:  Ectopic Notch activation in developing podocytes causes glomerulosclerosis in transgenic mice.  J Am Soc Nephrol 2008 19:1139-57.  SRA

De S, Al-Nabhani D, Thorner P, Cattran D, Piscione TD, Licht C:  Remission of resistant MPGN type I with mycophenolate mofetil and steroids. Pediatr Nephrol. 24:597-600, 2009.    Col
Xu K, Nieuwenhuis E, Cohen B, Wang W, Canty AJ, Danska J, Coultas L, Rossant J, Wu MY, Piscione TD, Nagy A, Gossler A, Hicks GG, Hui CC, Henkelman RM, Yu LX, Sled JG, Gridley T, Egan SE.  Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis.  Am J Physiol Lung Cell Mol Physiol. 2010 298(1):L45-56.   Col