Benny Geiger's Lab

(In collaboration with Prof. Eldad Tzahor, Department of Biological Regulation)

The heart is the first organ to be formed in the vertebrate embryo. Heart formation is a very complex process, susceptible to defects. Congenital heart disease is the most common birth defect, arising from abnormalities in early stages of cardiogenesis. After birth, ischemic heart disease, myocardial infarction in particular, is the most common heart ailment. In higher vertebrates, cardiomyocytes (CM) are believed to lack renewal and regenerative potential: they cease to proliferate shortly after birth, and from then on, the heart grows in a hypertrophic manner. However, in lower vertebrates (such as fish), the heart preserves its regenerative potential, employing a dedifferentiation mechanism by means of which CMs re-enter the cell cycle. Recent studies indicate that CMs of higher vertebrates are also able to regenerate, to some extent. The heart's ability to proliferate is limited by the presence of a myofibrillar structure, the sarcomer, that facilitates CM contractility. The ultimate goal of our work is to elucidate the molecular mechanisms underlying CM proliferation, differentiation and dedifferentiation, and to facilitate CM renewal and repair. First, we will establish purified cultures of CMs (initially from chicken, followed by rat and mouse) at various stages. Next, a variety of mechano-transduction manipulations will be tested for their ability to affect myocardial differentiation and dedifferentiation. We will then perform mechanobiology-based screens for conditions that induce CM proliferation, which will be examined by various imaging and immunostaining techniques. Signaling strategies, combined with microenvironmental manipulations and biomechanical signals, will be employed to disrupt the balance of CM proliferation vs. differentiation, thus favoring their proliferative potential.