This broad research group provides students with training in a variety of subjects related to nucleic acid metabolism. The Division of Basic Science has a strong group of interactive faculty interested in the enzymology of DNA replication and in RNA metabolism, particularly the post-transcriptional regulation of gene expression. Considerable progress is being made in understanding the complex mechanisms involved in prokaryotic DNA replication and now, eukaryotic DNA replication systems, including the most intricate replication processes in human cells. Also, it is now recognized that the majority of gene regulation occurs at the post-transcription level. Accordingly, there is an active effort to identify and understand the function of the myriad protein and RNA factors that control the maturation, transport, stability and translation of mRNAs. Specific areas of research investigated by our mentor faculty include the molecular mechanism of DNA replication termination and DNA repair, mRNA transport, regulation of mRNA turnover and control of translation, alterations in post-transcriptional control of gene expression in cancer, micro RNA structure and function, and nucleic acid:protein interactions. In these studies a variety of model systems are used by our faculty, including yeast, leukemia cell lines, chronic lymphocytic leukemia patient samples, prostate cell lines, and mouse model systems of breast cancer. These exciting studies are contributing important insights into the control of cell proliferation, the response of cells to apoptotic signals, and the role of mRNA stability in aberrant gene expression in cancer pathogenesis and in periodontal disease.

Students have access to several faculty with primary interests in functional metabolomics and enzymology, focused in the areas of lipid, folate, and methyl group metabolism. Trainees with a focus in lipidomics will acquire solid expertise in both the foundations of lipidology (e.g., lipid chemistry, lipid enzymology, lipid metabolism, lipid structure, lipid trafficking, lipid-protein interactions, mechanisms of lipid signaling, structure and function of membrane proteins and lipid-regulated proteins) and its translational components, primarily cardiovascular disease and inflammation, mitochondrial energetics, intermediary metabolism, and lipoproteins. Trainees with interests in folate and methyl metabolism will acquire solid expertise in the enzymes of folate metabolism, methyl group metabolism, and basic structural enzymology.

Trainees will acquire a solid foundation in the mechanisms that cells utilize to maintain homeostasis and to respond to extracellular signals (e.g. hormones, growth factors, neurotransmittors, etc.). How cells receive, process and transduce these signals into intracellular responses is an area of active investigation in the Basic Science Division. Signal transduction pathways amplify and integrate diverse external signals and then generate a variety of biochemical responses that can alter gene expression, enzyme activities or ion channel activity, for example. Specific areas of research of our mentors include G proteins and G protein receptors, protein kinases (e.g. the MAP kinase family), growth factor signaling (IGF and VEGF), phospholipases, heat shock proteins (HSP90), reactive oxygen species and RNA regulatory proteins. Since fundamental cell processes such as cell growth are regulated through signal transduction mechanisms, aberrant signaling processes are associated with a variety of diseases. Research in our mentor faculty laboratories is contributing to understanding the relationships of specific signaling pathways to angiogenesis and cell migration, cell proliferation and cancer pathogenesis, chemotherapeutic drug resistance, reactive oxygen species (ROS)-induced malignancies and quantitative signaling networks.