Department of Physiology
Basic Sciences Building
New York Medical College
Valhalla, NY 10595
Dr. Eisenberg’s research program focuses on the generation and maintenance of the myocardium in the embryo and adult, with the specific emphasis on the role that epigenetic regulation and Wnt signal transduction play in promoting cardiac cell differentiation. The laboratory’s recent studies over the past few years have been on the importance of G9a histone methyltransferase (HMTase) in regulating the phenotypic potential of adult stem cells. Specifically, we have shown that inhibition of G9a HMTase-mediated histone methylation can shift the differentiation potential of non-cardiac stem cells, such as bone marrow mesenchymal stem cells, to a cardiac competent phenotype. The suppression of G9a HMTase activity in non-cardiac stem cells allows the cells to respond to cardiogenic differentiation factors and exhibit a gene and protein expression profile similar to nascent cardiomyocytes. Among the most prominent of these cardiac differentiation factors are the WNT family of secreted signaling proteins, which have been shown to play important roles in regulating cell fate decisions of stem cells. WNT regulation is essential for brain, limb, kidney, mammary gland, muscle and heart development and their dysregulation has a major influence on tumor formation. Ongoing investigations in the laboratory examine how combinatorial signaling by distinct classes of WNT proteins promote cardiogenesis and allow non-cardiac stem cells to undergo cardiac differentiation following the inhibition of G9a histone methyltransferase.
Post Graduate Studies: University of Pennsylvania, The Rockefeller University
Graduate Degree: Ph.D.
Graduate Degree Institution: University of Chicago
Undergraduate Institution: University of Pennsylvania
Eisenberg, L. M., P. W. Ingham, and A. M. C. Brown. 1992. Cloning and characterization of a novel Drosophila Wnt gene, Dwnt-5, a putative downstream target of the homeobox gene Distal-less. Developmental Biology 154:73-83. PMID: 1358729
Eisenberg, L. M., and Markwald, R. R. 1995. Molecular regulation of atrioventricular valvuloseptal morphogenesis. Circulation Research 77:1-6. PMID: 7788867
Eisenberg, C. A. and L. M. Eisenberg. 1999. WNT11 promotes cardiac tissue formation of early mesoderm. Developmental Dynamics 216:45-58. PMID: 10474165
Eisenberg, L. M. 2002. Belief versus scientific observation: the curious story of the precardiac mesoderm. The Anatomical Record 266:194-197. PMID: 11920381
Eisenberg, L. M. and R. R. Markwald. 2004. Cellular recruitment and the development of the myocardium. Developmental Biology 274: 225– 232. PMID: 15385154
Eisenberg, L. M. and C. A. Eisenberg. 2006. WNT signal transduction and the formation of the myocardium. Developmental Biology 293:305-315. PMID: 16563368
Eisenberg, C. A., J. B. Burch and L. M. Eisenberg. 2006. Bone marrow cells transdifferentiate to cardiomyocytes when introduced into the embryonic heart. Stem Cells 24:1236-1245. PMID: 16410395
Martin, L. K., N. V. Mezentseva, M. Bratoeva, A. F. Ramsdell, C. A. Eisenberg, and L. M. Eisenberg. 2011. Canonical WNT signaling enhances stem cell expression in the developing heart without a corresponding inhibition of cardiogenic differentiation. Stem Cells and Development 20: 1973-1983. PMID: 21351874
Mezentseva, N. V., J. Yang, G. Iaffaldano, M. C. Rémond, K. Kaur, C. A. Eisenberg, and L. M. Eisenberg. 2013. The histone methyltransferase inhibitor BIX01294 enhances the cardiac potential of bone marrow cells. Stem Cells and Development 22(4):654-667. PMID: 22994322
Kaur, K., J. Yang, C. A. Eisenberg, and L. M. Eisenberg. 2014. 5-azacytidine promotes the transdifferentiation of cardiac cells to skeletal myocytes. Cellular Reprograming 16:324-30. PMID:25090621
Yang, J., K. Kaur, L. L. Ong, C. A. Eisenberg, and L. M. Eisenberg. 2015. Inhibition of G9a histone methyltransferase converts bone marrow mesenchymal stem cells to cardiac competent progenitors. Stem Cells International 2015:270428. doi: 10.1155/2015/270428. PMID: 26089912
Kaur, K., J.Yang, J. G. Edwards, C. A. Eisenberg, and L. M. Eisenberg. 2016. The G9a histone methyltransferase inhibitor BIX01294 promotes the expansion of adult cardiac progenitor cells without changing their phenotype or differentiation potential. Cellular Proliferation 49:373-385. doi: 10.1111/cpr.12255. PMID: 27109896
Yang, J., K. Kaur, L., J. G. Edwards, C. A. Eisenberg, and L. M. Eisenberg. 2017. Inhibition of histone methyltransferase, histone deacetylase and β-catenin synergistically enhance the cardiac potential of bone marrow cells. Stem Cells International 2017:3464953. doi: 10.1155/2017/3464953. PMID: 28791052
Borghetti, G., C. A. Eisenberg, S. Signore, A. Sorrentino, K. Kaur, A. A. Andrade, J. G. Edwards, M. Nerkar, K. Qanud, D. Sun, P. Goichberg, A. Leri, P. Anversa, L. M. Eisenberg, J. T. Jacobson, T. H. Hintze, and M. Rota. 2018. Notch signaling modulates the electrical behavior of cardiomyocytes. American Journal of Physiology, Heart Circulation Physiology 2017 314:H68-H81. doi: 10.1152/ajpheart.00587.2016. PMID: 28939651
Eisenberg, C. A. and L. M. Eisenberg. 2019. G9a and G9a-like histone methyltransferases and their effect on cell phenotype, embryonic development, and human disease. In “The DNA, RNA, and Histone Methylomes, vol. 9,” p399-433. S. Jurga and J Barciszewski, ed., Springer Nature, Switzerland, pub.