Thomas SneiderProfessor Emeritus

The research pursued during my tenure at Colorado State University grew out of my prior research on the role of ethionine in mammalian hepatocarcinogenesis. Ethionine interfers with multiple aspects of one carbon metabolism and our goal was to investigate how that might be connected to converting mitotically quiescent liver cells to a state of heritable but uncontrolled proliferation. We first used a double isotopic labeling approach to demonstrate conclusively for the first time that post-replication modification of DNA occurred in eukaryotic cells and that that modification was sequence specific. Proceeding from that discovery we next looked for the enzymatic activity needed to catalyze the conversion of specific DNA-cytosine residues to 5-methylcytosone residues. The eukaryotic DNA methylase from rat hepatoma [cholangiocarcinoma] cells was partially purified and analyzed with respect to its sequence specificity. In the process, the methylation sequence sensitivity  of the microbial restriction endonucleases Hpa II and MspI were delineated as tools useful in analyzing methylation sites in any DNA vis a vis transcription. Further research using 5-aza-cytosine as an inhibitor of DNA methylation provided another approach to study the role of DNA methylation in regulation of cellular processes involved in replication and transcription. In addition to research, I was responsible for the establishment of the undergraduate major in Biochemistry, a major that is recognized as one of the premier science majors at CSU, as well as the experiential learning components of that major which were and are supported NSF REU grants. That, in turn, led me to develop the all-University Undergraduate Research Symposium that started in 1994 and continues to this date.