In 2012 Dr. Mathews closed his research laboratory, which had enjoyed extramural research support for more than 48 years at three different universities. The major research interest of the Mathews laboratory was the enzymology and regulation of DNA precursors, the deoxyribonucleoside triphosphates, or dNTPs.
Some of the questions explored by Dr. Mathews and his 35 Ph.D. students, plus postdoctoral associates, research assistants, and undergraduates, included the following:
- How are enzymes of dNTP synthesis organized within cells to facilitate the flow of intermediates into dNTPs and to maintain optimal dNTP concentrations at DNA replication sites in the face of rapid turnover as nucleotides are incorporated into DNA?
- How are dNTP pool sizes regulated within cells to support DNA replication at optimal rates and fidelity?
- By what mechanisms is genomic instability increased as a consequence of abnormal regulation of dNTP pools?
- What are the pathways supplying precursors for mitochondrial DNA replication in mammalian cells?
- To what extent does the high spontaneous mutation rate for the mitochondrial genome result from distinctive features of mitochondrial nucleotide metabolism?
As he continues in semi-retirement, Dr. Mathews has served as lead author of the textbook Biochemistry, published in 2012 in its fourth edition. More recently he has published, with two co-authors. two editions of a shorter textbook, Biochemistry: Concepts and Connections (2016 and 2019) Also he serves on several journal editorial boards, and he continues to teach one or two courses per year.