Kenneth S. Zaret
Senior Member and Program Leader
Epigenetics and Progenitor Cells Program
W.W. Smith Chair in Cancer Research
Adjunct Professor, Department of Genetics, U. Penn. Medical School

Genetics and Gene Regulation Program

Address

Cell and Developmental Biology Program
Fox Chase Cancer Center
Room W410
333 Cottman Avenue
Philadelphia, PA 19111

Office tel.: 215 728-7066
Lab tel.: 215 728-7067
Fax: 215 379-4305
E-mail: zaret@fccc.edu

Link(s)

Dr Zaret's Lab website

Education

University of Rochester, B.A. (Biology) 1977

University of Rochester Medical School,Ph.D. (Biophysics/Genetics) 1982

Research Interests

• Mammalian gene regulation
• cell differentiation
• chromatin structure

Key words: chromatin, gene regulation, transcription, differentiation, liver and pancreas development.

Description of Research

The goal of the laboratory 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, we 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, we 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.

Recent Publications

Zaret, K.S. (2008) Genetic programming of liver and pancreas progenitors: Lessons for stem cell differentiation. Nature Reviews Genetics 9, 329-340.

Sekiya, T., and Zaret, K.S. (2007) Repression by Groucho/TLE/Grg proteins: Genomic site recruitment generates compacted chromatin in vitro and impairs activator binding in vivo. Molecular Cell 28, 291-303.

Xu, J., Pope, S.D., Jazirehi, A.R., Attema, J.L., Papathanasiou, P., Watts, J. Zaret, K.S., Weissman, I.L., and Smale, S.T. (2007) Pioneer factor interactions and unmethylated CpG dinucleotides mark silent tissue-specific enhancers in embryonic stem cells. Proceedings of the National Academy of Sciences, USA 104, 12377-12382.

Calmont, A., Wandzioch, E., Tremblay, K.D., Minowada, G., Kaestner, K.H., Martin, G.R., and Zaret, K.S. (2006) An FGF-response pathway that mediates hepatic gene induction in embryonic endoderm cells. Developmental Cell 11, 339-348

Tremblay, K.D., and Zaret, K.S. (2005) Distinct populations of progenitor cells converge to generate the embryonic liver bud and other ventral gut tissues. Developmental Biology 280, 87-99.

Search PubMed for more articles

Lab

Rotation Projects

1. Biochemical and genetic analysis of cell signaling and transcription factor activation in mouse embryo tissues, during liver and pancreas cell specification.
2. Epigenetic regulation of developmental gene expression.
3. Mechanisms of transcription factor modulation of chromatin structure.
4. Genetic lineage tracing of different liver and pancreas progenitors.

Lab personnel:

Deborah Freedman-Cass, Ph.D. Senior Research Associate
Nandita Mullapudi, Ph.D. Postdoctoral Associate
Takashi Sekiya, Ph.D. Postdoctoral Associate
Ewa Wandzioch, Ph.D. Postdoctoral Associate
David Metzger, Ph.D. Postdoctoral Associate
Chengran Xu, Ph.D. Postdoctoral Associate
Jungsun Kim, Ph.D. Postdoctoral Associate
Jason Watts, MD-Ph.D. student, U. Penn School of Medicine
Andrea Wecker, B.A., M.S. Research Specialist
Angela Hynes, B.S. Research Assistant