Department of Pharmacology & Chemical Biology at the University of Pittsburgh
Dr. Alessandro Bisello
Associate Professor
W1356 Thomas E. Starzl Biomedical Science Tower
Pittsburgh, PA 15261

Email:
alb138@pitt.edu
Phone: 412-648-7347

Fax: 412-648-3290


Education

Laurea (Chemistry), University of Padova, Italy, 1992
Postdoctoral Fellow, Biopolymer Research Center, University of Padova, Italy, 1992-1994
Postdoctoral Fellow, Beth Israel Deaconess Medical Center, Harvard Medical School, 1994-1996



Research Areas
Receptor Pharmacology
Signal Transduction
Pharmacology of Cell and Organ Systems
Cardiovascular and Renal Pharmacology
Photo of Dr. Alessandro Bisello

The general scientific theme in the laboratory is to define the role of accessory/scaffolding proteins (such as caveolin and EBP50/NHERF1) in the regulation of cellular and tissue functions. Our efforts focus on two specific areas:
 
1) Role of EBP50/NHERF-1 on vascular remodeling.  The Ezrin-Radixin-Moesin Binding Phosphoprotein of 50 kDa (EBP50), also known as NHERF-1 is a PDZ domain-containing scaffolding protein. Our studies show that EBP50 is expressed at low levels in healthy vessels but is up-regulated following arterial injury. EBP50 contributes to the proliferation of vascular smooth muscle cells (VSMC). The temporal expression of EBP50 following arterial injury and its ability to regulate specific cell cycle proteins and signaling receptors suggest that this adaptor protein plays a key role in the integrated response of VSMC to injury. Current studies aim at determining the role of EBP50 on vascular remodeling.
 
Expression of PTHrP and EBP50 in restenotic carotid arteries. Sections from rat carotid arteries 2 weeks after angioplasty were fixed and immunostained for PTHrP (upper panels) or EBP50 (lower panels) (in green). Nuclei were visualized with DRAQ5 (in red). Scale bars, 50 mm.















 

 

2) Cellular regulation of the glucagon-like peptide 1 (GLP-1R) receptor and its role in regulating beta cell function, proliferation and survival. One of the most promising therapeutic targets for the treatment of type 2 diabetes is the glucagon-like peptide 1 receptor (GLP-1R). The well documented ability of GLP-1R agonists, either GLP-1 itself or exendin-4, to stimulate glucose-dependent insulin secretion and increase beta cell proliferation and survival led to the approval of exendin-4 for the treatment of type 2 diabetes. Our studies show that the GLP-1R interacts with caveolin-1 and this is necessary for the trafficking of the GLP-1R to the cell membrane and directs its localization to lipid rafts. The central hypothesis of this project is that the interaction between GLP-1R and caveolin-1 and its localization in lipid rafts is a fundamental mechanism controlling both the insulinotropic and the proliferative actions of GLP-1 and exendin-4.


GLP-1R and caveolin-1. HEK293 cells stably expressing GLP-1R-GFP (green) were stimulated with exendin-4. Cells were fixed, immunostained for caveolin-1 (in red), and examined by confocal fluorescence microscopy. Extensive internalization of the GLP-1R-GFP occurs and the internalized GLP-1R-GFP colocalizes with caveolin-1.





Important Publications
Leslie KL, GJ Song, S Barrick, VL Wehbi, JP Vilardaga, PM Bauer and A Bisello.  Ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) and nuclear factor kB (NF-kB):  A feed-forward loop for systemic and vascular inflammation.  J Biol Chem 2013 Nov. 6 [Epub ahead of print].
Al Ghouleh I, G Frazziano, AI Rodrigues, G Csanyi, S Maniar, CM St. Croix, EE Kelley, LA Egana, GJ Song, A Bisello, YJ Lee and PJ Pagano.  Aquaporin 1, Nox1 and Ask1 mediate oxidant-induced smooth muscle cell hypertrophy.  Cardiovasc Res 97:134-142, 2013.
Wang B, CK Means, Y Yang, T Mamonova, A Bisello, DL Altschuler, JD Scott and PA Friedman.  Ezrin-anchored protein kinase A coordinates phosphorylation-dependent disassembly of a NHERF-1 ternary complex to regulate hormone-sensitive phosphate transport.  J Biol Chem 287:24148-14163, 2012.
Song GJ, S Barrick, KL Leslie, PM Bauer, V Alonso, PA Friedman, NM Fiaschi-Taesch and A Bisello.  The scaffolding protein EBP50 promotes vascular smooth muscle cell proliferation and neointima formation by regulating Skp2 and p21cip1.  Arterioscler Thromb Vasc Biol 32:33-41, 2012.
Song GJ, KL Leslie, S Barrick, S Bougoin, JM Taboas and A Bisello.  EBP50 promotes focal adhesion turnover and vascular smooth muscle cells migration.  J Mol Cell Cardio 53:809-819, 2012.
Song GJ, S Barrick, KL Leslie, B Sicari, NM Fiaschi-Taesch and A Bisello.  EBP50 inhibits the anti-mitogenic action of the parathyroid hormone type 1 receptor in vascular smooth muscle cells.  J Mol Cell Cardiol 49:1012-2021, 2010.
Song GJ, N Fiaschi-Taesch and A Bisello. Endogenous parathyroid hormone-related protein regulates the expression of PTH type 1 receptor and proliferation of vascular smooth muscle cells. Mol Endocrinol 23:1681-1690, 2009.
Syme CA, L Zhang and A Bisello. A. Caveolin-1 regulates cellular trafficking and function of the glucagon-like peptide 1 receptor. Molecular Endocrinology 20:3400-3411, 2006.




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