Research in the lab is directed toward understanding early embryonic development of blood and heart, using a variety of experimental systems. The focus is on the function and regulation of a small group of highly conserved transcriptional regulatory proteins called GATA factors.

GATA factors were first discovered as hematopoietic regulatory proteins. GATA-1 is essential for erythropoiesis (red blood cell development), and appears to function as a survival and differentiation factor. In contrast, GATA-2 is important for survival and proliferation of an earlier progenitor cells. Because GATA factors are conserved across vertebrate evolution, the studies are relevant to diseases in humans such as leukemia, in which hematopoietic cells fail to differentiate properly.

We are trying to discover how embryonic signaling pathways control the regulation of these genes and then how the GATA factors control embryonic erythropoiesis. Our current hypothesis is that BMP-4 is a growth factor for embryonic erythropoiesis (perhaps analogous to erythropoietin in the definitive (adult stage) blood system. Some of the current projects in the lab related to embryonic erythropoiesis include:

Three members of the GATA factor family, called GATA-4/5/6, are first expressed in the embryonic progenitors that will form the heart. They are some of the earliest known genes to be important for cardiogenesis. Although it was originally thought that they control primarily cardiomyocyte differentiation, we and others have found that they also regulate heart morphogenesis. Our recent studies show that GATA-4 is a critical mediator of the retinoic acid pathway in the developing heart. In addition to the frog, the chick embryo is useful for these studies because the chick embryonic heart is so well characterized and gene expression can be manipulated.

We are also involved in collaborative studies using mouse, rat, and human systems to understand the role of GATA factors during disease, and to try and find new genes that GATA factors regulate in the cardiovascular system. For example, GATA-6 is important for regulating vascular smooth muscle cell proliferation.

Recently, we established the Einstein Zebrafish Facility. The zebrafish is an exciting and powerful genetic experimental system that has been called the "Drosophila of vertebrates", because genetic approaches can be used to find new genes and define genetic pathways; this is not possible using other vertebrate systems like frogs or mice. Currently, we are growing and mating fish, and establishing in the lab fish transgenic techniques. We hope that the project grows into a facility that will have widespread interest to the Einstein community.

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