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A Message from the Director

The Center for Transgene Research at the University of Notre Dame was established in 1995 to develop and employ mice with designed gene alterations to study functions of components of the hemostasis system in a variety of genetic diseases.  It was renamed the W. M. Keck Center for Transgene Research in 1998, after receipt of funding from the W. M. Keck Foundation to significantly expand its infrastructure. 

The mission of the center is to develop and use gene-targeting technology to investigate the pathophysiological roles of the genes of the blood coagulation, anticoagulation, and fibrinolytic pathways in hemostasis, with associated relevance to embryonic development, cancer, infection, and inflammation.  Toward this end, the foci of the center have been directed in several complementary programs.  One major effort of the center is to use novel gene-targeting and transgenic strategies, as well as sophisticated genetic manipulations, to generate mice with partial and complete deficiencies, as well as modifications of several hemostasis genes. 

The Notre Dame W. M. Keck Center is maintaining perhaps the largest collection of mice with modified hemostatic systems in the world.  A major effort of this Center is to employ these hemostasis-altered animal models to study several acute and chronic inflammatory diseases (particularly, sepsis, atherosclerosis, asthma, cancer, and neurodegenerative maladies) in order to understand mechanistically the basis of the critically important crosstalk between hemostasis and inflammation. 

This effort has involved use of novel animal models developed by us and by colleagues around the world.  Lastly, a number of strategies have been designed to rescue these gene deficiencies and their associated phenotypes.  Among these are development of animals with multiple gene deletions, wherein the absence of one gene may lead to a correction of a more serious phenotype expressed by deficiency of another gene, development of animals with gene modifications that may attenuate a more serious phenotype, and use of techniques of molecular and cellular biochemistry to insert new forms of genes that may assist in alleviating the phenotypes associated with the diseases of interest. 

In the end, it is our hope to understand the molecular basis of diseases which rank among the leading causes of mortality and morbidity of humans, with the expectation that novel diagnostic and subsequent interventional strategies can be designed for humans.

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Francis J. Castellino, PhD
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean emeritus, College of Science
University of Notre Dame