Giovanni Ferrari

faculty photo
Research Assistant Professor of Surgery
Member, Institute for Translational Medicine and Therapeutics (ITMAT)
Principal Investigator of the Human Tissue Collection Database, Cardiovascular Surgery Division, Department of Surgery
Department: Surgery

Contact information
Children’s Hospital of Philadelphia
Abramson Research Building, Suite 702E
3615 Civic Center Blvd, Philadelphia, PA 19104-4318
Philadelphia, PA 19104
Office: 215 590 2459
Fax: 215 590 5454
Lab: 215 590 6098
Education:
M.S. (Molecular Biology)
University of Pavia, Italy & Italian National Research Council, 1999.
Ph.D. (Genetics & Cell Biology)
University of Pavia, Italy & Italian National Research Council, 2004.
N/A
Institute for Advanced Study of Pavia, Italy (IUSS), 2004.
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Description of Itmat Expertise

Aortic Valve Stenosis: Mechanisms of Calcification and Development of Biological Markers: Recent studies demonstrate that the even in the absence of clinical symptoms the thickening of the aortic valve leaflets is a pathological condition predisposing to several cardiovascular disease including chronic heart failure (CHF), myocardial infarction (MI) and, most prevalently, severe calcific aortic valve stenosis. Due to its asymptomatic presentation and to the fact that these valve are not replaced until symptoms occurs, little is known about the mechanisms of pathological remodeling.
We aim to characterize the molecular mechanism leading to aortic valve remodeling from physiological to pathological condition. Our projects on aortic valve disease integrate a highly complex phenomenon to develop a rational basis for future therapeutic strategies targeting subclinical aortic disease. Secondary to this, we are investigating cellular and molecular targets that can help the risk-stratification of patients to identify “fast” and “slow” progressors, and therefore understand why only a subgroup of patients with develop symptomatic aortic stenosis.

Cellular Physiology of Myxomatous Mitral Valve Prolapse: Heart valve disease at this time can only be treated surgically; no mechanism-based therapeutic strategies exist. The prolapse of the Mitral Valve (MV) leaflet is a hallmark of several disorders affecting this cardiac valve, such as myxomatous mitral valve disease (MMVD) or the pseudo-prolapse in chronic ischemic mitral regurgitation (MR). We are investigating the cellular and molecular mechanisms leading to Mitral Valve Disease. The overall goal of these studies is to identify therapeutic candidates for treating MMVD. The line of research could have major application in the diagnostic and clinical management of MV patients. First, our genetic data could be applied, in conjunction with imaging analysis, to risk-stratify Mitral Valve patients for the likelihood of developing early valvular disease. Second, our investigations could be applied to type of surgical intervention (repair vs. replacement); although the reoccurrence of MV disease is very low after repair of the MV, information of the likelihood of pathological remodeling may be taken into consideration. Most importantly, the results of this grant may generate important data on the pharmacological treatment of patients developing MMVD.

Molecular Determinants of Thoracic Aortic Aneurysm in Bicuspid and Trileaflets Aortic Valve: It is estimated that about one in 50 people are born with a bicuspid aortic valve (BAV). In the United States, a child is born with BAV every seven minutes, making BAV the most common congenital heart defect in the country. A bicuspid aortic valve is an aortic valve with only two leaflets instead of three. Patients with this congenital heart defect are at higher risk of developing calcification of the aortic valve, a condition requiring surgical intervention. Current clinical and scientific studies are also revealing that bicuspid aortic disease is not a simple valve condition, but it affects the aorta as well. A dissection or rupture of the aorta is a catastrophic event, with extremely high mortality, even if it occurs inside a hospital. Currently, the only diagnostic method to detect the presence of a BAV is echocardiography or other imaging techniques and no diagnostic or risk-stratification tools are available to label BAV patients for the risk of ascending aortopathies. Our laboratory has recently developed a method to test the progression of BAV-associated aortopathies. In addition, we are characterizing the molecular and cellular mechanisms responsible for the weakening of the aortic wall in both BAV and tricuspid aortic valve (TAV) patients. This research has an important outcome for public health: it will provide physicians and scientists a tool to identify a patient population at high risk of valvular and vascular pathologies. Low risk patients could be spared costly follow-up or surgical intervention, while high-risk patients could be followed intensively both clinically and surgically. In addition, it provides new mechanistic insights into the development of cardiovascular diseases in this prevalent population.

Description of Other Expertise

External Collaborations:

- The Valley Hospital Foundation, Ridgewood, NJ (Dr Juan B Grau)
- U of Texas at Austin, TX (Dr Michael S Sacks)
- Dana Farber Cancer Center, Harvard U, MA (Dr John Quackenbush)
- U of Milan, Centro Cardiologico Monzino, Italy (Dr Alessandro Parolari)
- U of Pavia, Italy (Dr Alessandra Montecucco)
- New York University, NY (Dr Paolo Mignatti)

Description of Research Expertise

Cardiovascular Medicine, Aortic Valve Disease, Mitral Valve Disease, Aortic Aneurysm, Angiogenesis, Tissue Engineering, Biomaterials, Cell Biology, Molecular Biology

Dr Ferrari's Lab supports a broad range of basic and translational science research projects in order to improve diagnosis, treatment, and prevention of cardiovascular disease.

Current Full-Time Lab Members:

Emanuela Branchetti, PhD - Postdoctoral Fellow
Kathryn Driesbaugh, PhD - Postdoctoral Fellow
Eric K Lai - Research Specialist

Undergraduate and Part-Time Lab Members:

Selected Publications

Poggio, Paolo, Sainger, Rachana, Branchetti, Emanuela, Grau, Juan B, Lai, Eric K, Gorman, Robert C, Sacks, Michael S, Parolari, Alessandro, Bavaria, Joseph E, Ferrari, Giovanni: Noggin attenuates the osteogenic activation of human valve interstitial cells in aortic valve sclerosis. Cardiovascular research. Oxford University Press, 2013.

Branchetti, Emanuela, Poggio, Paolo, Sainger, Rachana, Shang, Eric, Grau, Juan B, Jackson, Benjamin M, Lai, Eric K, Parmacek, Michael S, Gorman, Robert C, Gorman, Joseph H: Oxidative stress modulates vascular smooth muscle cell phenotype via CTGF in thoracic aortic aneurysm. Cardiovascular research 100(2): 316-324, November 2013.

Branchetti, Emanuela, Sainger, Rachana, Poggio, Paolo, Grau, Juan B, Patterson-Fortin, Jeffrey, Bavaria, Joseph E, Chorny, Michael, Lai, Eric, Gorman, Robert C, Levy, Robert J, Giovanni Ferrari: Antioxidant Enzymes Reduce DNA Damage and Early Activation of Valvular Interstitial Cells in Aortic Valve Sclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB) 33(2): 66-74, Feb 2013.

Ferrari, Giovanni, Terushkin, Vitaly, Wolff, Martin J, Zhang, Xiaodong, Valacca, Cristina, Poggio, Paolo, Pintucci, Giuseppe, Mignatti, Paolo: TGF-β1 Induces Endothelial Cell Apoptosis by Shifting VEGF Activation of p38MAPK from the Prosurvival p38β to Proapoptotic p38α Molecular cancer research : MCR. American Association for Cancer Research, 10(5): 605-614, 2012.

Poggio Paolo, Grau Juan B, Field Benjamin C, Sainger Rachana, Seefried William F, Rizzolio Flavio, Ferrari Giovanni: Osteopontin controls endothelial cell migration in vitro and in excised human valvular tissue from patients with calcific aortic stenosis and controls. Journal of cellular physiology 226(8): 2139-49, Aug 2011.

Grau Juan B, Poggio Paolo, Sainger Rachana, Vernick William J, Seefried William F, Branchetti Emanuela, Field Benjamin C, Bavaria Joseph E, Acker Michael A, Ferrari Giovanni: Analysis of osteopontin levels for the identification of asymptomatic patients with calcific aortic valve disease. The Annals of thoracic surgery 93(1): 79-86, Jan 2012.

Sainger Rachana, Grau Juan B, Branchetti Emanuela, Poggio Paolo, Seefried William F, Field Benjamin C, Acker Michael A, Gorman Robert C, Gorman Joseph H, Hargrove Clark W, Bavaria Joseph E, Ferrari Giovanni: Human myxomatous mitral valve prolapse: Role of bone morphogenetic protein 4 in valvular interstitial cell activation. Journal of cellular physiology Nov 2011.

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Last updated: 04/07/2014
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