Alda Tufro MD, PhD
Associate Professor of Pediatrics (Nephrology); Section Chief, Pediatric Nephrology
Molecular and developmental biology; VEGF-A; Semaphorins; Proteinuria; Slit-diaphragm proteins; Protein interactions; Signaling pathways; Cyst development; Vascular patterning; Podocyte differentiation
Functions of VEGF-A in podocytes: implications for renal disease
VEGF-A and diabetic nephropathy
VEGF-A and nephrosis during development
Role of class 3 semaphorins in kidney development and disease
The molecular mechanisms of proteinuria in kidney diseases that lead to renal failure are poorly understood. Our research focuses on the role of a guidance protein called semaphorin3a, and on vascular endothelial growth factor (VEGF-A), an important angiogenic factor, on kidney development and disease. We discovered that excess semaphorin3a causes proteinuria and this molecule is essential for the correct assembly and maintenance of the kidney filters. Our experiments in semaphorin3a genetically engineered mice provide new information to understand at the cell and molecular level how semaphorin3a causes proteinuria, and identify kidney diseases mediated by semaphorin3a. We also discovered that excess VEGF-A in a specific kidney cell type from adult mice mimics diabetic nephropathy, whereas in newborn mice it causes a minimal change-like disease. Our experiments in VEGF-A transgenic mice are advancing the understanding of diabetic nephropathy in adults and nephrotic syndrome in children, and should enable us to design new strategies for treatment of diabetic nephropathy and glomerular diseases.
- Bertuccio C, Veron D, Aggarwal PK, Holzman L, Tufro A. Vascular endothelial growth factor receptor 2 direct interaction with nephrin links VEGF-A signals to actin in kidney podocytes.
J Biol Chem. 2011 Nov 18;286(46):39933-44.
- Veron D, Bertuccio CA, Marlier A, Reidy K, Garcia AM, Jimenez J, Velazquez H, Kashgarian M, Moeckel GW, Tufro A. Podocyte vascular endothelial growth factor (Vegf164) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes. Diabetologia. 2011 May;54(5):1227-41.
- Veron D, Reidy K, Marlier A, Bertuccio C, Villegas G, Jimenez J, Kashgarian M, Tufro A. Induction of podocyte VEGF164 overexpression at different stages of development causes congenital nephrosis or steroid-resistant nephrotic syndrome. Am J Pathol. 2010 Nov;177(5):2225-33.
- Veron D, K Reidy, J Teichman, G Villegas, J Jimenez, W Shen, J Kopp, D Thomas, A Tufro. Overexpression of VEGF-A in podocytes of adult mice causes glomerular disease. Kidney International, March 10, 2010; doi:10.1038/ki.2010.64.
- K Reidy, Veron D, J Teichman, G Villegas, J Jimenez, W Shen, D Thomas, A Tufro. Semaphorin3a regulates endothelial cell number and podocyte differentiation during glomerular development. Development. 2009 Dec;136(23):3979-89.
- Tufro A, J Teichman, C Woda, G Villegas. Semaphorin 3A inhibits ureteric bud branching morphogenesis in vitro. Mech of Dev, 125(5-6):558-68, 2008.
- Tapia R, Teichman J, Gershin I, Villegas G, A Tufro. Semaphorin 3A disrupts podocyte foot processes and induces acute proteinuria. Kidney International, 73(6):733-40, 2008.
- Tufro A, Teichman J, Villegas G,. Crosstalk between VEGF-A/VEGFR2 and GDNF/RET signaling pathways. Biochem Biophys Res Commun 358(2):410-416, 2007.
- Banu N, Teichman J, Villegas G and A Tufro. Semaphorin 3C regulates endothelial cell function by increasing integrin activity. FASEB J 20:E1520-E1527, 2006.
- Guan, F., Villegas, G., Teichman, J., Mundel P., A. Tufro. Autocrine VEGF system in podocytes regulates podocin and its interaction with CD2AP. Am J Physiol Renal, Aug;291(2):F422-8, 2006.