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Center for Research on Cardiac Intermediate Filaments

Principal Investigator: Giulio Agnetti, PhD, FAHA
Laboratory Manager: Timothy Starosta, BS

Laboratory Location:

Johns Hopkins University School of Medicine
720 Rutland ave, Ross 10

Research Focus

The CRCIF was established to foster collaborative efforts aimed at elucidating the role of intermediate filaments (IFs) in the heart. Intermediate filaments constitute a class of cytoskeletal proteins in metazoan cells, however, different from actin microfilaments and tubulin microtubules, their function in cardiac cells is poorly understood. Unique from the other two components of the cytoskeleton, IFs are formed by cell type-specific proteins. Desmin is the main component of the IFs in the cardiac myocytes. We measured the consistent induction of desmin post-translational modifications (PTMs, such as phosphorylation, etc.) in various clinical and experimental models of heart failure. Therefore, one of our main focuses is to determine the contribution of desmin PTMs to the development of heart failure in different animal and clinical models.

Active Projects:

• Quantification of desmin PTM-forms in different forms of heart failure at the peptide level using mass spectrometry
• Functional assessment of the role of desmin PTMs in heart failure development using single site mutagenesis and biophysical methods
• Molecular characterization of desmin preamyloid oligomers using mass spectrometry, in vitro and in vivo imaging
• Assessment of the diagnostic and pharmacological value of desmin PTMs in heart failure development

Laboratory Collaborators:

Selected Bibliography:

1. Agnetti G (lead editor), Lindsey ML, Foster DB. “Manual of Cardiovascular Proteomics”, Springer Ed. 2016

2. Agnetti G, Dunn MJ. “A Historical Perspective on Cardiovascular Proteomics” Manual of Cardiovascular Proteomics, Springer Ed. 2016 (book chapter)

3. Di Silvestre D, Brambilla F, Agnetti G and Mauri P. “Bottom-Up Proteomics” Manual of Cardiovascular Proteomics, Springer Ed. 2016 (book chapter)

4. Wright I, Agnetti G and Van Eyk JE. “Mass Spectrometry: Bridging the Gap from Discovery to Patient Care” Manual of Cardiovascular Proteomics, Springer Ed. 2016 (book chapter)

5. Mercurio V, Pirozzi F, Lazzarini E, Marone G, Rizzo P, Agnetti G, Tocchetti CG, Ghigo A, Ameri P. Models of Heart Failure Based on the Cardiotoxicity of Anticancer Drugs. J Card Fail. 2016 Apr 18. pii: S1071-9164(16)30023-9. doi: 10.1016/j.cardfail.2016.04.008. [Epub ahead of print] Review. PubMed PMID: 27103426.

6. Agnetti G, Piepoli MF, Siniscalchi G, Nicolini F. New Insights in the Diagnosis and Treatment of Heart Failure. Biomed Res Int. 2015;2015:265260. doi:10.1155/2015/265260. Epub 2015 Oct 26. Review. PubMed PMID:6634204; PubMed Central PMCID: PMC4637457.

7. Subramanian K, Gianni D, Balla B, Assenza GE, Joshi M, Semigran M, MacGillivray TE, Van Eyk JE, Agnetti G, Paolocci N, Bamburg J, Agrawal P, del Monte F. Cofilin-2 Phosphorylation and Sequestration in Myocardial Aggregates: Novel Pathogenetic Mechanisms for Idiopathic Dilated Cardiomyopathy. J Am Col Cardiol. 2015 Mar 31;65(12):1199-214. doi: 10.1016/j.jacc.2015.01.031. Erratum in: J Am Coll Cardiol. 2015 May 12;65(18):2056. PubMed PMID: 25814227; PubMedCentral PMCID: PMC4379451.

8. Del Monte F, Agnetti G. Protein Post-Translational Modifications and Misfolding: New Concepts in Heart Failure. Proteomics Clinical Application. 2014 Aug;8(7-8):534-42. PubMed PMID: 24946239

9. Agnetti G, Halperin-Kuhns V, Kirk J, Chakir K, Guo Y, Lund L, Nicolini F, Gherli T, Guarnieri C, Caldarera CM, Kass DA, Tomaselli GF, Van Eyk JE. Desmin modifications associate with amyloid-like oligomers deposition in heart failure. Cardiovasc Res. 2014 Apr 1;102(1):24-34. PubMed PMID: 24413773; PubMed Central PMCID: PMC3958618.

10. Kirk JA, Holewinski RJ, Viola Kooij VK, Agnetti G, Tunin RS, Witayavanitkul N, de Tombe PP, Gao W, Van Eyk JE, Kass DA.Cardiac Resynchronization Sensitizes the Sarcomere to Calcium by GSK-3β activation. J Clin Invest. 2014 Jan2;124(1):129-38. PubMed PMID: 24292707; PubMed Central PMCID: PMC3871225.