Ph.D. Analytical Toxicology, University of Utah 2001
B.S. Chemistry, Walla Walla College, WA 1997
1. Analysis of Protein and Lipid Glycosylation
For many years cancer biologists have recognized that, as a general rule, tumor cells display aberrant glycan (sugar polymer) structures. This means that if glycans can be analyzed in the right way(s), they should serve as excellent markers for the presence and progression of cancer. Altered activity of the enzymes that build glycans (glycotransferases, GTs) is the immediate upstream cause of abnormal glycan production. GTs build glycans in an opportunistic non-template driven, first-come-first-build way, with each type of GT adding a specific sugar residue to a specific position of a growing glycan "tree". Thus increased expression of a particular GT results in an increased number of specific glycan polymer branch points (or linear linkages) and a highly diverse set of final glycan structures. We have invented a new gas chromatography-mass spectrometry (GC-MS) based technique to quantify N-, O-, and lipid-linked glycans in whole biofluids and tissues on the basis of these specific glycan polymer branch points and linkages rather than on the basis of intact glycan structure. This provides a means for condensing interesting glycan features into single analytical signals as well as a direct surrogate readout for GT activity. As such, it represents a promising new angle by which to leverage glycans as cancer biomarkers.
2. Protein Posttranslational Modifications (PTMs)
Many if not most proteins are molecularly modified after translation. Abnormal protein modification may exist as either a cause or an effect of disease; it therefore warrants exploration as a potentially rich source of disease markers. In combination with optimized sample preparation techniques, modern bioanalytical tools such as mass spectrometry are now capable of routinely characterizing and quantifying the relative abundance of most protein PTMs. Yet caution is warranted as certain protein modifications-oxidative PTMs in particular-may arise as artifacts of less-than-optimal sample handling, potentially confounding their use as disease markers and interfering with conventional clinical laboratory tests based on binding interactions (e.g., ELISAs where protein quantification is based on interaction of the target protein with an antibody). We are interested in tracking protein modifications due to artifactual oxidation, determining how they affect conventional clinical laboratory tests, and figuring out how to prevent them from occurring.
Chad Borges is an assistant professor with joint appointments in the School of Molecular Sciences and The Biodesign Institute. He received a B.S. in chemistry from Walla Walla College (WA) in 1997. He went on to complete a Ph.D. in Analytical Toxicology (2001) at the University of Utah under Professor Douglas Rollins, the medical director in charge of doping control for the 2002 Olympic Games. His dissertation research focused on the role of hair pigments and cellular transport in drug incorporation into hair. He continued his education as a postdoctoral fellow at Michigan State University under pioneering mass spectrometrist J. Throck Watson, where he studied protein mass spectrometry with an emphasis on characterizing protein posttranslational modifications. In 2003, he returned to Utah where he helped establish the Olympic-level certified Sports Medicine Research and Testing Laboratory. Following successful laboratory accreditation, he transitioned to the Biodesign Institute at ASU in 2007 where he worked for several years as a research faculty member with Dr. Randall Nelson before joining the Department of Chemistry & Biochemistry (now School of Molecular Sciences) in 2013. Professor Borges? research interests include development and application of a new form of bottom-up glycomics recently developed by his group; developing molecular markers of biospecimen integrity; and characterization of protein posttranslational modifications as indicators of disease and physiological function.