J. Peter Gergen
Ph.D., Brandeis University, 1982
Associate Professor, Department of Biochemistry and Cell Biology
Research Interests: Regulation of gene expression and the genetics of development.
The long term goal of the research program in this laboratory is to understand
fundamental mechanisms involved in metazoan development. This research is
founded in the genetically tractable model system Drosophila melanogaster,
and has focused for some time on the role of a key developmental regulator,
the Runt gene. This gene was originally identified and characterized due
to its vital role in the process of Drosophila segmentation. Subsequent
work from this laboratory revealed that Runt also has independent functions
in the pathways of sex determination and neurogenesis. In the segmentation
and sex-determination pathways the Runt protein acts to regulate the transcription
of other genes.
Recently a family of mammalian proteins that share a significant region
of homology with the Drosophila Runt protein has been identified. This homology
region, referred to as the Runt-domain, is a novel type of DNA-binding domain
that also mediates hetero-dimerization with an unrelated partner protein.
Although the full developmental roles of these mammalian homologues are
not known, they are thought to function as transcriptional regulators during
embryogenesis and in hematopoiesis. Interestingly, chromosome rearrangements
that break within one of the human homologues of Runt, the AML1 gene are
associated with myeloid leukemia.
Our current research takes advantage of the wealth of information on early
Drosophila development to investigate the regulation of gene expression
by the Runt protein. We have selected different target genes that are known
to be transcriptionally regulated by Runt for these studies. This includes
the Sex-lethal gene in the sex determination pathway as well as several
different genes (even-skipped, hairy, and fushi tarazu) from the segmentation
pathway. In each case the regulation of these genes depends on interactions
between Runt and other transcriptional regulatory proteins. We are using
a combination of biochemical and both molecular and classical genetic approaches
to investigate these interactions. These studies will provide fundamental
information on the developmental regulation of gene expression in normal
development and should give insights on how cancer results from a breakdown
in these mechanisms.
Kagoshima, H., Shigesada, K., Satake, M., Ito, Y., Miyoshi, H., Ohki, M.,
Pepling, M. and Gergen, J.P. (1993) The Runt-domain identifies a new family
of heteromeric transcriptional regulators. Trends in Genetics 9: 338-341.
Tsai, C. and Gergen, J.P. (1994) Gap gene properties of the pair-rule gene
Runt during Drosophila segmentation.
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