Contact Information:
Department of Biochemistry
Michigan State University
East Lansing, MI 48824-1319
halgren@pilot.msu.edu

Education

B.S. Biochemistry (Honors), Michigan State University, 1992.
Ph.D. Cancer Biology, Northwestern University, 1998.

Research Project

My current research interests are in the field of toxicogenomics and bioinformatics. Toxicogenomics is a relatively new discipline, combining the technology of examining hundreds (or thousands) of genes simultaneously (genomics) with traditional toxicology techniques. It is expected that a given toxicant will induce a distinct pattern of gene expression within its target cell or tissue, and that we can use this information to correlate gene expression with physiologic effects. More interestingly, these techniques make it possible to gain information about the mechanisms of action for a given toxicant, assign function to previously uncharacterized genes, and develop rapid throughput assays for the screening of suspected toxic chemicals. We are applying these techniques to a number of different experimental problems.

A good example of toxicogenomics is an ongoing project which is designed to examine the effects of polychlorinated biphenyl (PCB) or environmental estrogen exposure during fetal and neonatal development on the fertility of male mice. In this case, we expect to see a change in the quantity or quality of sperm obtained from mice exposed to PCBs or estrogens, as well changes in other endpoints such as testis weight or morphology. In addition to this traditional toxicology approach, we also examine the gene expression profiles of the mouse testis using a genomics based approach, and correlate the changes in the gene expression patterns with changes in sperm quantity or quality, or other physiologic endpoints such as change in testis weight. We initially examined gene expression using commercially available cDNA arrays containing approximately 600 different cDNAs, however these arrays are not specific to the murine testis and hence only yield limited information.

Due to the limitations of commercially available arrays, we have initiated the construction of testis specific cDNA arrays, containing only genes which are known to be expressed in the mouse testis. By this approach, we hope to obtain a better understanding of gene expression in the testis of the mouse after exposure to any environmental toxicant. To facilitate this, we have created dbTEST (database of Transcripts Expressed in Spermatogenesis and Testis). This library is constructed using a bioinformatics (data mining) based approach, wherein we are searching computer based resources such as the Mouse Unigene database (National Center for Biotechnology Information) and the mouse Gene Expression Database (Jackson Laboratories), and combining these with an extensive search of the literature for genes that have been shown to be expressed in the testis. So far, we have compiled a list of approximately 5000 known genes, which we are using to create our own high density cDNA arrays.