Dr. Felix Engel

Sofja Kovalevskaja Junior Research Group

Heart Development and Regeneration

Group leader

Felix Engel, Ph.D. > mail

Contact

Sofja Kovalesvskaja Junior Research Group
Max-Planck-Institute for Heart and Lung Research
Parkstraße 1
61231 Bad Nauheim
Germany
Tel.: +49 (6032) 705-248 (office)
Tel.: +49 (6032) 705-253 (lab)
Mobile: +49 (171)2237444
Fax: +49 (6032) 705-211

Research Overview

It is generally believed that the human heart cannot regenerate. Instead, following injury, human hearts scar. This inadequate regenerative response contributes significantly to morbidity and mortality. In the developed world, the prognosis for patients with symptomatic heart failure is worse than that associated with most cancers - about 30 percent mortality rate within 1 year. One of the reasons for this poor outlook is the fact that conventional treatment regimen fail to correct the problem of cardiomyocyte loss. By contrast with humans, zebrafish and newt faithfully regenerate many of their organs including heart. Interestingly, heart regeneration is in both cases based on cardiomyocyte proliferation. Dr. Engel and his colleagues are therefore working to identify mechanisms that regulate cardiomyocyte proliferation during heart development and allow the induction of proliferation in adult mammalian cardiomyocytes. In previous experiments, they have accumulated evidence that postnatal mammalian cardiomyocytes can divide. They have identified p38 MAPK as a key negative regulator of cardiomyocyte proliferation. Furthermore, they have shown that p38 inhibition enhances the proliferative capacity of neonatal and adult cardiomyocytes after growth factor stimulation.

Dr. Engel imagines that his work will result in a therapy for heart failure patients and congenital heart disease. In addition, he hopes to discover pathways allowing regeneration of organs other than the heart.

Major goals of Dr. Engel's research include:
• to define the molecular mechanisms of cardiomyocyte proliferation
• to induce cardiomyocyte proliferation in vivo
• to induce cardiac regeneration in mammals and finally in humans

Group Members

Post Docs

Florian Diehl > mail
Tatyana Novoyatleva > mail
Machteld van Amerongen > mail

PhD-Students

Ajit Magadum > mail
Chinmoy Patra > mail

Master-Students

Mirela Bortmes > mail

Technical Assistants

Ingrid Hauck-Schmalenberger > mail

About Felix Engel

Felix Engel received his PhD from Technical University Berlin and completed postgraduate training at Children's Hospital Boston / Harvard Medical School. Awards include Children's Hospital (Boston) Research Day Award (2005), a Charles H. Hood Foundation Child Health Research Grant $150.000 ($75.000 per year from 2006-2007), and the Sofja Kovalevskaja Award 1.100.000 Euro (12/06 to 12/10).

Selected Publications

Engel FB, Hauck L, Cardoso MC, Leonhardt H, Dietz R, von Harsdorf R.
A mammalian myocardial cell-free system to study cell cycle reentry in terminally differentiated cardiomyocytes.
Circ Res. 1999; 85(3):294-301.
link to pdf

Engel FB, Hauck L, Boehm M, Nabel EG, Dietz R, von Harsdorf R.
P21CIP1 controls proliferating cell nuclear antigen protein level in adult cardiomyocytes.
Mol Cell Biol. 2003; 23(2):555-65.
link to pdf

Gresch O, Engel FB, Nesic D, Tran TT, England HM, Hickman ES, Körner I, Gan L, Chen S, Castro-Obregon S, Hammermann R, Wolf J, Müller-Hartmann H, Nix M, Siebenkotten G, Kraus G, Lun K.
New non-viral method for gene transfer into primary cells.
Methods, 2004; 33(2):151-63.
link to journal website

Philippar U, Schratt G, Dieterich C, Muller JM, Galgoczy P, Engel FB, Keating MT, Gertler F, Schule R, Vingron M, Nordheim A.
The SRF Target Gene Fhl2 Antagonizes RhoA/MAL-Dependent Activation of SRF.
Mol Cell. 2004; 16(6):867-80.
link to pdf

Engel FB, Schebesta M, Duong MT, Lu G, Ren S, Madwed JB, Jiang H, Wang Y, Keating MT.
p38 MAP Kinase Inhibition Enables Proliferation of Adult Mammalian Cardiomyocytes.
Genes & Dev.2005; 19(10):1175-87.
link to pdf
link to Supplmental Research Data

Schebesta M, Lien CL, Engel FB, Keating MT.
Transcriptional Profiling of Caudal Fin Regeneration in Zebrafish. Scientific World Journal Development & Embryology.
2006; 1(S1):38-54.
link to pdf

Engel FB, Schebesta M, Keating MT.
Anillin Localization Defect in Cardiomyocyte Binucleation.
J Mol Cell Cardiol, 2006; 41(4):601-612 (Cover, Editorial).
link to journal website

Tseng AS, Engel FB, and Keating MT.
The GSK-3 Inhibitor BIO Promotes Proliferation in Mammalian Cardiomyocytes.
Chemistry & Biology. 2006; 13(9):957-63.
link to pdf
link to Supplemental Data

Engel FB, Hsieh PCH, Lee RT, and Keating MT.
FGF1/p38 MAP kinase inhibitor therapy induces cardiomyocyte mitosis, reduces scarring and rescues function after myocardial infarction.
Proc Natl Acad Sci U S A. 2006; 103(42):15546-51.
link to pdf
link to Supporting Information

Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, Wassen FWJS, Crescenzi A, da-Silva WS, Harney J, Engel FB, Obregon MJ, Larsen PR, Bianco AC, Huang SA.
Hypoxia-inducible factor induces local thyroid hormone inactivation in hypoxic-ischemic disease.
J Clin Invest. 2008;118(3):975-983.
link to pdf

Novoyatleva T, Diehl F, van Amerongen MJ, Patra C, Ferrazzi F, Bellazzi R and Engel FB.
TWEAK is a positive regulator of cardiomyocyte proliferation.
Cardiovasc Res. 2009; ; doi: 10.1093/cvr/cvp360.
link to pdf

van Amerongen MJ, Diehl F, Novoyatleva T, Patra C and Engel FB.
E2F4 is required for cardiomyocyte proliferation.
Cardiovasc Res. 2009; doi: 10.1093/cvr/cvp383.
link to pdf


Reviews:
Engel FB.
Cardiomyocyte Proliferation: A Platform for Mammalian Cardiac Repair.
Cell Cycle. 2005; 4:1360-63.
link to pdf

van Amerongen MJ and Engel FB.
Features of cardiomyocyte proliferation and its potential for cardiac regeneration.
J Cell Mol Med. 2008; 12(6a):2233-44.
link to journal webpage