Brief Description of Current Research Interests (1) Characterization of the “injury-resistant” cardiac state: We have established that the low molecular weight FGF-2 exerts a powerful protection of the rat heart from ischemia and reperfusion injury and dysfunction, even when administered after the onset of ischemia; the magnitude of protection is similar to that of preconditioning or post-conditioning manipulations. We are investigating the signal transduction mechanisms mediating FGF-2 cardioprotection. We have identified the gap junction protein connexin43, and its phosphorylation at specific sites, as a downstream target of FGF-2 signaling, and are now investigating their role in the induction as well as maintenance of protection.(2) Cardiac Repair-Regeneration:
We have demonstrated that a single administration of low molecular weight FGF-2 during the development of myocardiac infarction induces results in substantial improvement in heart function and decrease in tissue loss both acutely and long-term. We are investigating the hypothesis that low molecular weight FGF-2 stimulates stem-cell based cardiac regeneration.(3) Cardiac cell death – hypertrophy
We have discovered that the high molecular weight FGF-2 isoform causes cell death in an intracrine manner, and hypertrophy in an auto- or para-crine manner. We are investigating the mechanisms involved.(4) Regulation of and by Connexin-43
We are investigating the role of connexin-43, the main cardiomyocyte gap junction protein, in the regulation of cardiomyocyte signaling relating to growth and gene expression. This project uses engineered Cx43 mutations and deletions to alter the properties of the molecule and is accompanied by proteomics studies to identify interacting partners of connexin-43 in the normal versus ‘stressed’ state.
SELECTED RECENT PEER-REVIEWED PUBLICATIONS
1. Santiago JJ, Ma X, McNaughton L, Nickel BE, Yu L, Fandrich RR, Netticadan T, Kardami, E. Preferential accumulation and release of high molecular weight FGF-2 by rat cardiac non-myocytes. Epub ahead of print, Cardiovascular Research, 2010
2. Santiago JJ, Dangerfield A, Rattan S, Bathe KL, Cunnington R, Raizman J, Bedosky KM, Freed D, Kardami E, Dixon IMC. Cardiac fibroblast to myofibroblast differentiation in vitro:expression of focal adhesion components in neonatal and adult rat ventricular myofibroblasts. Dev.Dynamics, 239, 1573-84, 2010
3. Srisakuldee W, Jeyaraman MM, Nickel BE, Tanguy S, Jiang Z-S, Kardami E. Phosphorylation of cardiac connexin-43 at serine 262 promotes an injury-resistant state. Cardiov.Res. 83, 672-81, 2009
4. Ma X, Dang X, ClausP, Hirst, Fandrich RR, Jin Y, GrotheC, KirshenbaumL, CattiniPA and Kardami E. Chromatin compaction and cell death by high molecular weight FGF-2 depend on its nuclear localization, intracrine activation of ERK1/2 and engagement of mitochondria. Journal of Cellular Physiology 213, 690-698, 2007.
5. Jiang ZS, Jeyaraman M, Wen G-B, Fandrich RR, Dixon IAC, Cattini PA and Kardami E. High- but not low-molecular weight FGF-2 causes cardiac hypertrophy in vivo: Possible involvement of cardiotrophin-1. J Mol Cell Cardiol 42:222-233, 2007.
6. Jiang ZS, Jeyaraman M, Wen G-B, Fandrich RR, Dixon IAC, Cattini PA and Kardami E. High- but not low-molecular weight FGF-2 causes cardiac hypertrophy in vivo: Possible involvement of cardiotrophin-1. J Mol Cell Cardiol 42:222-233, 2007.
7. JiangZS, Srisakuldee W, Soulet F, Bouche G and Kardami E. Non-angiogenic FGF-2 protects the ischemic heart from injury, in the presence or absence of reperfusion. Cardiovasc Res 62:154-166, 2004
8. Doble BW, Dang X, Ping P, Fandrich RR, Nickel BE, Jin Y, Cattini PA and Kardami E. Phosphorylation of serine 262 in the gap junction protein connexin-43 regulates DNA synthesis in cell-cell contact forming cardiomyocytes. J Cell Sci 2004 117:507-514, 2004
9. Jeyaraman M, Tanguy S, Fandrich RR, Lukas A and Kardami E. Ischemia-induced dephosphorylation of cardiomyocyte connexin-43 is reduced by okadaic acid and caliculin A but not fostriecin. Mol Cell Biochem 242:129-134, 2003
10. Dang X, Doble BW and Kardami E. The carboxy-tail of connexin-43 localizes to the nucleus and inhibits cell growth. Mol Cell Biochem 242, 35-38, 2003
11. Jiang Z-S, Padua RR, Ju H, Doble BW, Jin Y, Hao-J, Cattini PA, Dixon IMC and Kardami E. Acute protection of the ischemic heart by FGF-2; involvement of FGF-2 receptors and protein kinase C. Am J Physiol 282:H1071-H1080, 2002
12. Sheikh F, Sontag DP, Kardami E and Cattini PA. Exogenous addition and endogenous overexpression of FGF-2 increases cardiac myocyte viability after myocardial injury in isolated mouse hearts. Am J Physiol 280:H1039-H1050, 2001
13. Doble BW, Ping P and Kardami E. The epsilon subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation. Circ Res 86:293-301, 2000
For a complete list please refer to the following link and search for “Kardami E”: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed
