Our laboratory is interested in Genetic Variations as related to cancer. One focus is on mutations and polymorphisms in the human genome that may be rate-limiting towards cancer. Small differences between people's DNA are called "single nucleotide polymorphisms" (SNPs). It is believed that some SNPs result in alterations of the cellular function and may be important to cancer. Another focus of the laboratory is on changes in the protein composition of the cell as related to cancer. This holistic approach to look at the cell is call "proteomics". Using 2D gel proteomics, we have identified about 1,700 proteins in the human colon crypt proteome and discovered pathway alterations in a colon cancer-prone syndrome called familial adenomatous polyposis. In collaboration with the gastroenterology group of FCCC, we are extending our analysis to cancers of the pancreas and upper GI. We also contributed to the science of mutation detection with our patented CEL I mismatch endonuclease. CEL I, a nuclease isolated from celery, is capable of identifying a single mismatch in a million basepairs of DNA (Oleykowski et al., Nucl. Acids Res. 26:4597, 1998; Sokurenko, et al., Nucl. Acids Res. 29:E111, 2001; Yeung et al., BioTechniques 38:749, 2005). It is used to detect unknown mutations in genes important to cancer, in pathogen evolution, and in a reversed-genetics approach called Tilling.