My research is dedicated to the study of genetics of heart muscle diseases, called cardiomyopathies. Since 1991, we have collected clinical information and DNA of over 1700 subjects from families with cardiomyopathies, initially in Italy and subsequently in the USA. Data and materials are collected in the International Familial Registry which has been supported by various grants of the NIH, AHA, UN, MDA. Through our researches on the molecular genetics of cardiomyopathies and analysis on genotype-phenotype correlations, several genes and pathways causing heart disease have been investigated in my laboratory, from cytoskeletal and sarcomeric genes, to ion channels. We are interested in the genes causing dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia, left ventricular noncompaction and hypertrophic cardiomyopaty. Among the most important accomplishments are the discovery of dilated cardiomyopathy genes, such as lamin A/C (LMNA) associated with variable muscular involvement, LAP2, SCN5A and MYH6, and the recent discovery of the titin gene (TTN), the largest gene of the human genome, as a cause of arrhythmogenic right ventricular cardiomyopathy.
We are also interested in genotype-phenotype association studies, which are critical to transfer bench-to-bedside knowledge. Our ongoing research has shown that specific genes may have a different prognosis and may suggest different management strategies. Functional studies of mutant cardiomyopathy genes are also performed to evaluate the consequences of the defective proteins on cellular models. We are currently exploring applications of nanotechnology and bioengineering to the study of heart function and cardiomyopathies.
My laboratory collaborates with a network of local and international investigators, in particular Dr. Matthew Taylor, Adult Medical Genetic Program, Dr. Carlin Long, Cellular Biology Cardiovascular Institute, Dr. John Caldwell, Department of Cell and Molecular Biology, and investigators at the University of Trieste and Florence in Italy under the auspices of two bilateral agreements.
Selected recent publications (2008-2011)
Taylor M, Graw S, Sinagra G, Barnes C, Slavov D, Brun F, Pinamonti B, Salcedo EE, Sauer W, Pyxaras S, Anderson B, Simon B, Bogomolovas J, Labeit S, Granzier H, Mestroni L.
Genetic Variation in Titin in Arrhythmogenic Right Ventricular Cardiomyopathy-Overlap Syndromes.
Circulation. 2011 Aug 1. [Epub ahead of print] PubMed PMID: 21810661.
Mestroni L, Taylor MR.
Pharmacogenomics, personalized medicine, and heart failure.
Discov Med. 2011 Jun;11(61):551-61. PubMed PMID: 21712021.
Mestroni L, Taylor MR.
Hearing the noise the challenges of human genome variation in genetic testing.
J Am Coll Cardiol. 2011 Jun 7;57(23):2328-9. PubMed PMID: 21636033.
McNair WP, Sinagra G, Taylor MR, Di Lenarda A, Ferguson DA, Salcedo EE, Slavov D, Zhu X, Caldwell JH, Mestroni L;
Familial Cardiomyopathy Registry Research Group.
SCN5A mutations associate with arrhythmic dilated cardiomyopathy and commonly localize to the voltage-sensing mechanism.
J Am Coll Cardiol. 2011 May 24;57(21):2160-8. PubMed PMID: 21596231.
Pinamonti B, Dragos AM, Pyxaras SA, Merlo M, Pivetta A, Barbati G, Di Lenarda A, Morgera T, Mestroni L, Sinagra G.
Prognostic predictors in arrhythmogenic right ventricular cardiomyopathy: Results from a 10-year registry.
Eur Heart J. 2011 May;32(9):1105-13. Epub 2011 Feb 28. PubMed PMID: 21362707.
Mestroni L, Merlo M, Taylor MR, Camerini F, Sinagra G.
Heart failure and personalized medicine.
J Cardiovasc Med (Hagerstown). 2011 Jan;12(1):6-12. Review. PubMed PMID: 20814312.
Moretti M, Merlo M, Barbati G, Di Lenarda A, Brun F, Pinamonti B, Gregori D, Mestroni L, Sinagra G.
Prognostic impact of familial screening in dilated cardiomyopathy.
Eur J Heart Fail. 2010 Sep;12(9):922-7. Epub 2010 Jun 4. PubMed PMID: 20525703.
Mestroni L. Phenotypic heterogeneity of sarcomeric gene mutations: a matter of gain and loss?
J Am Coll Cardiol. 2009 Jul 21;54(4):343-5. PubMed PMID: 19608032; PubMed Central PMCID: PMC2756576.
Hershberger RE, Lindenfeld J, Mestroni L, Seidman CE, Taylor MR, Towbin JA;
Heart Failure Society of America. Genetic evaluation of cardiomyopathy--a Heart Failure Society of America practice guideline.
J Card Fail. 2009 Mar;15(2):83-97. PubMed PMID: 19254666.
Taylor MR, Slavov D, Humphrey K, Zhao L, Cockroft J, Zhu X, Lavori P, Bristow MR, Mestroni L, Lazzeroni LC.
Pharmacogenetic effect of an endothelin-1 haplotype on response to bucindolol therapy in chronic heart failure.
Pharmacogenet Genomics. 2009 Jan;19(1):35-43. PubMed PMID: 18953265; PubMed Central PMCID: PMC3035051.
Mestroni L, Taylor MR. Lamin A/C gene and the heart: how genetics may impact clinical care.
J Am Coll Cardiol. 2008 Oct 7;52(15):1261-2. PubMed PMID: 18926330; PubMed Central PMCID: PMC2571955.
12: Sinagra G, Di Lenarda A, Moretti M, Mestroni L, Pinamonti B, Perkan A, Salvi A, Pyxaras S, Bussani R, Silvestri F, Camerini F.
The challenge of cardiomyopathies in 2007.
J Cardiovasc Med (Hagerstown). 2008 Jun;9(6):545-54. Review. PubMed PMID: 18475121.
Amat di San Filippo C, Taylor MR, Mestroni L, Botto LD, Longo N.
Cardiomyopathy and carnitine deficiency.
Mol Genet Metab. 2008 Jun;94(2):162-6. Epub 2008 Mar 11. PubMed PMID: 18337137; PubMed Central PMCID: PMC2430214.
Zecchin M, Di Lenarda A, Gregori D, Merlo M, Pivetta A, Vitrella G, Sabbadini G, Mestroni L, Sinagra G.
Are nonsustained ventricular tachycardias predictive of major arrhythmias in patients with dilated cardiomyopathy on optimal medical treatment?
Pacing Clin Electrophysiol. 2008 Mar;31(3):290-9. PubMed PMID: