Karim Si-Tayeb, PhD
Postdoctoral Fellow Department of Cell Biology, Neurobiology & Anatomy
PhD, University Victor Segalen Bordeaux, France, 2004
Faculty Advisor: Stephen Duncan, D Phil
Mailing Address: Department of Cell Biology, Neurobiology & Anatomy 8701 Watertown Plank Road Milwaukee, WI 53226-3548 USA
Email: ksitayeb@mcw.edu Phone: (414) 456-8336 FAX: (414) 456-6517
Research Area: Application of human embryonic stem cells as a genetic model for developmental and pathological studies of endodermally derived tissues
After formation of the three principal cellular layers--ectoderm, endoderm and mesoderm-- during the early stages of embryonic development, complex crosstalk signalizations occurs. The first consequence is a specification of cellular territory followed by an induction into a cell fate that precedes organogenesis. Our laboratory is interested in the development of endodermally derived organs, specifically the liver and more recently the gut and pancreas. As early hepatic specification requires signals from the precardiac mesoderm and mesenchymal cells from the septum transversum, we have also developed an interest in the mesoderm region where they come from, lateral plate and lateral mesoderm respectively.
While some members of our team study the transcriptional regulation that underlie those processes during the mouse development, my project focuses on the specification and induction of the endodermal tissues in hepatic and pancreatic fate in human development and their implications in a pathologic context. Many developmental aspects that are well known in the mouse remain obscure in human. Moreover, several human diseases have no equivalent in mouse, or can not be studied with this model. To facilitate the study of human development and diseases, we propose the approach of using human embryonic stem cells as an experimental model.
The first step of my project is to define and establish the best conditions for the culture and the maintenance of pluripotency and renewal of huesc on feeders. By establishing feeder-free culture conditions, we will be able to define conditions that initiate differentiation into mesodermal and endodermal fate. The establishment of genetically modified hues cell lines parallels the first part of my project, in that I will utilize pre-established hues cell lines in analyzing the consequences of introduced genetic modifications in a developmental and pathologic context.