Felix Engel, PhD
|Hospital Title||Associate Scientific Research|
|Academic Title||Instructor in Pediatrics|
300 Longwood Avenue
Boston MA 02115
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 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. 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
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) and a Charles H. Hood Foundation Child Health Research Grant $150.000 ($75.000 per year from 2006-2007).
- 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 2)
- Engel FB. Cardiomyocyte Proliferation: A Platform for Mammalian Cardiac Repair. Cell Cycle. 2005; 4:1360-63 3)
- 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.
|Adult mammalian cardiomyocytes are considered terminally differentiated and incapable of proliferation. Consequently, acutely injured mammalian hearts do not regenerate, they scar. However, adult mammalian cardiomyocytes can pharmacologically be induced to divide in vitro. The picture shows an adult rat cardiomyocyte treated with fibroblast growth factor 1 and an inhibitor of p38 MAP kinase in the final phase of cell division undergoing abscission. The cardiomyocyte was identified by an antibody against the contractile protein troponin T (red). Cleavage furrow ingression and abscission was visualized using an Aurora B antibody (green). DNA was stained with DAPI (blue). [Taken from: Engel FB, et al. p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev. 2005 May 15;19(10):1175-87. Epub 2005 May 3.]|