Kenneth S. Zaret
Associate Director, Institute for Regenerative Medicine
Department of Cell and Developmental Biology
University of Pennsylvania
1056 BRB II/III, 421 Circle Blvd., Philadelphia, PA 19104
1986 Searle Scholar
The goal of Dr. Zaret's lab research is to understand how genes are activated and different cell types are specified in embryonic development. These processes involve regulatory mechanisms that are used later in life to maintain human health, to respond to tissue damage, and during the initiation of cancers and other human diseases. The laboratory has two general approaches. First, to investigate the molecular signaling pathways that commit an undifferentiated embryonic cell, the endoderm, to a particular cell type fate, using the specification of liver and pancreas cells as a model. In the past year, Dr. Zaret and his team have developed a fate map of the foregut endoderm in the mouse embryo, we discovered how a gene regulatory protein controls morphogenesis so that endoderm cells are properly positioned to receive organ-inductive signals, and we found distinct roles for blood vessel cells in promoting the growth of liver and pancreatic tissues at the earliest stages of organ development. The second approach of the laboratory is to investigate ways that gene regulatory proteins control the packaging of DNA in the cell nucleus, to control gene activity. Biochemical studies revealed that the regulatory protein FoxA possesses a protein segment that interacts with chromosome structural proteins, or histones, and is necessary for exposing genes sequences in chromosomes that are otherwise hidden by the histone proteins. Understanding how regulatory proteins and cell signals control gene activity and cell type decisions in development will help guide future efforts to control the differentiation and function of cells at will.
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