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Translational Research In Cardiovascular Diseases

Giovanni Ferrari, PhD

Giovanni Ferrari, PhD

 

Office Address:
Assistant Professor
Perelman School of Medicine at the University of Pennsylvania
Children's Hospital of Philadelphia
Abramson Research Building, Suite 702E
3615 Civic Center Blvd.
Philadelphia, Pennsylvania
Telephone: 215-590-2459
Fax: 215-590-5454
Email: Giovanni.Ferrari@uphs.upenn.edu
 
Principal Investigator Bio:

Dr. Ferrari graduated from University of Pavia in Italy (2004).  Following his Ph.D. he was appointed Research Scientist at New York University where he began a series of studies examining the mechanisms of aortic valve remodeling and calcification.He then joined the University of Pennsylvania faculty to develop the program of Cardiovascular Translational Research, with the vision of merging molecular and cellular biology with clinical science applied to cardiovascular diseases. He has been leading this UPENN program for more then 5 years. Dr Ferrari is the author of 50+ scientific publications; he has been awarded several grants from both Federal and Private scientific associations. He serves as a reviewer for some of the most prestigious scientific journals and associations. He is a member of the American Heart Association and of the Society of Heart Valve Disease. He presented his research nationally and internationally and he holds two US patents for the diagnosis and treatments of valvular and vascular diseases. Dr Ferrari is also the PI of the Human Tissue Collection Program for the Division of Cardiovascular Surgery.

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 Research Projects:
  1. Aortic Valve Stenosis: 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.
  1. 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). 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); Most importantly, the results of this grant may generate important data on the pharmacological treatment of patients developing MMVD.

  2. 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. 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.
Selected Publications
  1. Aggarwal A, Ferrari G, Joyce E, Daniels MJ, Sainger R, Gorman JH 3rd, Gorman R, Sacks MS. Architectural Trends in the Human Normal and Bicuspid Aortic Valve Leaflet and Its Relevance to Valve Disease. Ann Biomed Eng. 2014 Feb 1;PubMed PMID: 24488233.
  2. Christian AJ, Lin H, Alferiev IS, Connolly JM, Ferrari G, Hazen SL, Ischiropoulos H, Levy RJ. The susceptibility of bioprosthetic heart valve leaflets to oxidation. Biomaterials. 2014 Feb;35(7):2097-102. PubMed PMID: 24360721; PubMed Central PMCID: PMC3937592.
  3. Branchetti E, Poggio P, Sainger R, Shang E, Grau JB, Jackson BM, Lai EK, Parmacek MS, Gorman RC, Gorman JH, Bavaria JE, Ferrari G. Oxidative stress modulates vascular smooth muscle cell phenotype via CTGF in thoracic aortic aneurysm. Cardiovasc Res. 2013 Nov 1;100(2):316-24. PubMed PMID: 23985903.
  4. Poggio P, Sainger R, Branchetti E, Grau JB, Lai EK, Gorman RC, Sacks MS, Parolari A, Bavaria JE, Ferrari G. Noggin attenuates the osteogenic activation of human valve interstitial cells in aortic valve sclerosis. Cardiovasc Res. 2013 Jun 1;98(3):402-10. PubMed PMID: 23483047; PubMed Central PMCID: PMC3656614.
  5. Branchetti E, Sainger R, Poggio P, Grau JB, Patterson-Fortin J, Bavaria JE, Chorny M, Lai E, Gorman RC, Levy RJ, Ferrari G. Antioxidant enzymes reduce DNA damage and early activation of valvular interstitial cells in aortic valve sclerosis. Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):e66-74. PubMed PMID: 23241403.
  6. Sainger R, Grau JB, Branchetti E, Poggio P, Seefried WF, Field BC, Acker MA, Gorman RC, Gorman JH 3rd, Hargrove CW 3rd, Bavaria JE, Ferrari G. Human myxomatous mitral valve prolapse: role of bone morphogenetic protein 4 in valvular interstitial cell activation. J Cell Physiol. 2012 Jun;227(6):2595-604. PubMed PMID: 22105615; PubMed Central PMCID: PMC3288540.
  7. Ferrari G, Terushkin V, Wolff MJ, Zhang X, Valacca C, Poggio P, Pintucci G, Mignatti P. TGF-β1 induces endothelial cell apoptosis by shifting VEGF activation of p38(MAPK) from the prosurvival p38β to proapoptotic p38α. Mol Cancer Res. 2012 May;10(5):605-14. PubMed PMID: 22522454; PubMed Central PMCID: PMC3356490.
  8. Grau JB, Poggio P, Sainger R, Vernick WJ, Seefried WF, Branchetti E, Field BC, Bavaria JE, Acker MA, Ferrari G. Analysis of osteopontin levels for the identification of asymptomatic patients with calcific aortic valve disease. Ann Thorac Surg. 2012 Jan;93(1):79-86. PubMed PMID: 22093695; PubMed Central PMCID: PMC3269243.
  9. Poggio P, Grau JB, Field BC, Sainger R, Seefried WF, Rizzolio F, Ferrari G. Osteopontin controls endothelial cell migration in vitro and in excised human valvular tissue from patients with calcific aortic stenosis and controls. J Cell Physiol. 2011 Aug;226(8):2139-49. PubMed PMID: 21520066; PubMed Central PMCID: PMC3523737.
  10. Parolari A, Tremoli E, Cavallotti L, Trezzi M, Kassem S, Loardi C, Veglia F, Ferrari G, Pacini D, Alamanni F. Do statins improve outcomes and delay the progression of non-rheumatic calcific aortic stenosis?. Heart. 2011 Apr;97(7):523-9. PubMed PMID: 21270077.

 

Lab Personnel
Principal Investigator
Giovanni Ferrari, PhD
Assistant Professor of Surgery
   
     
Lab Members
Emanuela Branchetti, PhD
Postdoctoral Fellow
Kathryn H. Driesbaugh, PhD
Postdoctoral Fellow
Eric K Lai
Research Specialist
     
Farrah Alkhaleel
Research Lab Assistant
Aseem Upadhhyay
Research Lab Assistant
 
 

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