Sophie Astrof, PhD
To learn more about Dr. Astrof’s background and how to contact her,
see her profile.
The main focus of the Astrof Laboratory is to understand cellular and molecular mechanisms of cardiovascular development in vertebrates. The heart is the first organ to form during embryogenesis. It's a complex and obviously, a very important organ. Congenital heart defects are among the most common and most severe birth defects in humans; and therefore, understanding basic details about how the heart and the vasculature form would undoubtedly lead to designing more effective therapies to treat congenital heart defects in the future.
Currently, the lab is working on three main areas:
1. Understand the function of tissue microenvironment during the development of the aorta, pulmonary artery and aortic arch arteries (AAAs)
These vessels constitute the arterial and pulmonary outflow from the heart, and the proper development of these vessels as well as their proper connectivity with the heart are absolutely crucial. We are interested in understanding how progenitors (also called stem cells) come together and assemble into a functional organ. In the case of blood vessels, endothelial cells comprising the inner layer of a vessel become surrounded by a coat of vascular smooth muscle cells (VSMCs), which are very important for the development and stability of a newly forming vessel. In the case of AAAs and distal portions of the aorta and pulmonary artery, the VSMCs are derived from the cardiac neural crest - a population of progenitor cells originating from the dorsal neural tube of an embryo. The proliferation, survival, migration and differentiation of these progenitors into VSMCs are tightly coupled to signals emitted by embryonic tissues located in the proximity to the cardiac neural crest migration routes.
One of the projects in the lab is to understand the nature of these signals. To that end, we are focusing on the role of fibronectin (FN), a large extracellular matrix protein. FN is synthesized by the cardiac neural crest progenitors and by distinct tissues, through which and near which the cardiac neural crest cells migrate. Therefore, we are performing both genetic and cell biological studies to understand the function of cell-autonomous and non cell-autonomous sources of FN during the development of the cardiac neural crest into VSMCs.
A complementary major project in this area is to understand how FN signal is received and the downstream consequences of FN signaling to cells. To accomplish this, we use genetics to specifically ablate a major cellular receptor for FN, called integrin α5β1, from specific embryonic tissues. Taken together, the combination of these two approaches will allow us to discern the origin, the role and the downstream effects of specific signals coming from embryonic microenvironments during the development of the cardiac neural crest progenitors into VSMCs.
2. Understand the function of tissue microenvironment during development of the vertebrate heart from cardiac progenitors
In mammals, cardiac progenitors are derived from the primitive streak. These cells migrate in the anterior direction on either side of the embryonic midline and come together to form a cardiac tube, which becomes more elaborated as progenitors from distinct embryonic locations are added to it. These cells migrate long distances and come in contact with distinct embryonic environments and signals, and we are using similar approaches as described above to study the signals and their downstream effectors during cardiac morphogenesis.
3.Mechanisms guiding embryonic patterning, and in particular, the development of embryonic left-right axis of asymmetry
Many visceral organs, including the heart, are asymmetrically positioned within the body, and defects in developing or maintaining the left-right body axis can lead to severe congenital abnormalities. We are using both the mouse and the fish as model systems to understand the role of extracellular matrix and its receptors during the development of the left-right asymmetry.