Frank J. Rauscher, III, Ph.D.
Institutional Affiliation:
Professor and Chairman
The Gene Expression and Regulation Program
Deputy Director, The Wistar Institute Cancer Center
http://www.wistar.org/research_facilities/rauscher/research.htm
Editor-In-Chief, The Journal, Cancer Research
Education
Moravian College, B.S.
Rowell Park Cancer Institute, SUNY, Buffalo, Ph.D.
Postdoctoral Work
Yale-New Haven Hospital – Chemotherapy Unit
Postdoctoral Work
Yale University School of Medicine – Medical Oncology
Postdoctoral Work
Roche Institute of Molecular Biology, Nutley, NJ – Department of Molecular Oncology
Research
Targeting the Sumoylation Machinery for Relief of Gene Silencing and Differentiation Therapy
Impact
The research I am pursuing is designed to achieve the complete definition of the molecular mechanisms in a cancer cell that silences genes and therefore causes cancer. We already know that reactivating these genes can be a very powerful and non-toxic therapy for these cancers. This paradigm has been pioneered and discovered by investigators of the SWCRF, which directly led to recognition and use of Retinoic Acid as a curative drug for leukemia. The problem now is that we need more targets for reversing gene silencing. This is the impact of my research: defining new targets for relief of gene silencing in cancers and then to use these targets to develop new drugs.
Summary of Research
The mission and aims of the SWCRF-Institute Without Walls are completely aligned with my career aims and goals. For the past twenty years I have been highly interested in targeting genes in cancers to achieve highly selective, non-toxic chemo-and differentiation-therapy.
A major impediment to achieving selective therapy is defining which genes are on or off in a particular tissue or tumor. The basis for this dichotomy in gene regulation is the following: Each of us is born with around 60,000 genes. However, only a fraction of those genes are turned on at any time in any particular tissue. These subsets of genes are turned on in particular tissues and function to make an eye an eye, a liver a liver, and a kidney a kidney (for instance). Thus, though each cell in the body has the exact same sixty thousand genes, a highly evolved process is present to only allow certain genes to be on and the vast majority of genes to be off (or silenced) in other tissues.
My laboratory is interested in the mechanisms whereby the human body can silence the vast majority of genes (in particular, normal tissues and in tumors). The best analogy that one could use to describe this biochemical phenomenon is the analogy between a computer’s hard drive and its software. The hard drive is the 60,000 genes that we inherit from our mothers and fathers.
However, each individual tissue and tumor type has a separate software package, which allows it to turn on or turn off a selective set of genes, which makes a kidney function or a brain function or a tumor form. This software acts largely at the level of gene regulation and the packaging of our genes into chromatin structures at the molecular level.
One can imagine that the computer’s hard drive is relatively immutable. However, the software in a particular tissue can be easily subverted and can have dire consequences. This is often what we see in the development and progression of cancer; that is, genes that are aberrantly expressed compared to the normal tissue. In order to understand this process and target it with drugs, we must identify the critical mechanisms the cell uses to maintain genes silencing and therefore define the cellular software that does that.
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