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Mathers Charitable Foundation Funds Fox Chase Research on New Approach to "Fingerprinting" Gene Packaging in a Cell

PHILADELPHIA (March 18, 2002)-A three-year, $660,000 grant from the G. Harold and Leila Y. Mathers Charitable Foundation of Mt. Kisco, N.Y., is supporting basic research at Fox Chase Cancer Center in the laboratory of cell and developmental biologist Kenneth S. Zaret, Ph.D.

The project, "Control of Gene Packaging in the Cell Nucleus," is pilot testing a new approach to identifying most active regulatory genes in a cell at the same time. Regulatory genes control a cell's functions by allowing it to produce only the proteins it needs when it needs them and to shut down unnecessary gene and protein activity.

Dr. Zaret, who lives in Elkins Park, Pa., became the first scientist to hold the Center's William Wikoff Smith Chair in Cancer Research when he came from Brown University to the Fox Chase basic science division as a senior member in 1999. The main focus of Zaret's laboratory is to understand how genes are activated and how different cell types are formed during development.

"A fundamental understanding of these mechanisms is critical for devising new approaches to maintain human health and prevent human disease," Zaret said. "We still have broad gaps in our knowledge about how genes are regulated and how regulation can go awry in disease states."

One of Zaret's experimental strategies is to investigate how the proteins governed by regulatory genes act to control genetic packaging-the chromatin structure in the nucleus of a cell-during the development of specific cell types. He uses both cell-culture (in vitro) and laboratory animal (in vivo) model systems, including an in vivo footprinting technique that allows scientists to visualize the interactions between DNA and proteins within living cells.

A report on studies that led to the Mathers-funded project appeared in the February 2002 issue of the prestigious journal Molecular Cell, which highlighted the article in its opening "Previews" section.

Mathers Charitable Foundation Funds Fox Chase Work on "Fingerprinting" Gene Activity/page 2 of 2

A goal of the research being funded by the Mathers grant is to understand how one regulatory factor binds to or disrupts a cell's chromatin-the tight bundle of rod-like chromosomes that package all the DNA, mixed with special proteins, at the heart of each cell. The factor Zaret is studying, HNF3, helps kick off production of regulatory genes' proteins by binding to very specific sites on the chromatin package.

Ultimately, Zaret hopes to develop and use a new approach to obtain a fingerprint of a cell's chromatin structure that would pinpoint most functioning regulatory genes simultaneously. The resulting information about chromosomes and chromatin structure would provide a different perspective and complement the data gained from current studies using DNA and RNA array ("gene chip") technology and protein expression (proteomics).

"There is no easy way to identify regulatory parts of genes except by labor-intensive studies of how they function," Zaret explained. "I have devised an approach to localize, in a single experiment, most of a cell's functional regulatory DNA sequences under virtually any physiological condition. The approach can be applied to any organism or tissue in which we can isolate the cell nuclei."

The grant for Zaret's current work on gene packaging fingerprints is the first Fox Chase has received from the Mathers Charitable Foundation. A private foundation established by G. Harold and Leila Y. Mathers in 1975, the Foundation works to support basic scientific research at various hospitals, medical research institutions and universities throughout the country.

Fox Chase Cancer Center, one of the nation's first comprehensive cancer centers designated by the National Cancer Institute in 1974, conducts basic and clinical research; programs of prevention, detection and treatment of cancer; and community outreach. For more information about Fox Chase activities, visit the Center's web site at or call 1-888-FOX CHASE.

Fox Chase Cancer Center, part of the Temple University Health System, is one of the leading cancer research and treatment centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence four consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach.  For more information, call 1-888-FOX CHASE or (1-888-369-2427).

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