PiezoBiosensor for Detecting Complex Environmental and Chemical Agents  This technology is an apparatus with multiple piezoelectric mass sensors for use in immunochemical detection of diagnostically relevant analytes. The detection is in real time, and each piezoelectric mass sensor comprises a piezoelectric crystal with a receptor surface containing recombinant antibodies that are specific for a particular antigen. The technology measures the binding of antigens to the recombinant antibodies by tracking a change in mass on the receptor surface which is detected as a change in resonant frequency. This technology emerged from a research program oriented toward developing piezobiosensors and electrochemical sensors for detection in complex environmental and clinical samples. The research program is focused on combining the excellent sensitivity of electrochemical and mass sensing with the superb selectivity of biological recognition processes (e.g., protein-protein interactions, DNA-protein interactions, carbohydrate-protein interactions). |
Center for Biomedical Research This center supports state-of-the-art research facilities for biomedical research, promotes and publicizes biomedical research, and aggressively encourages and supports initiatives for support of biomedical research. The center sponsors research presentations and colloquia, provides funds to support pilot research projects, and identifies novel funding. In addition, the center assists with the development and submission of proposals for external funding of major multi-investigator equipment, (b) provides and maintains readily accessible multi-user equipment facilities, and (c) facilitates access to specialized facilities and services. In addition to supporting and promoting collaborations among its members, the center facilitates interactions between members and other institutions, including pharmaceutical and biotechnology companies, and promotes access to biomedical research equipment within the center. |
Linoleic Acid This research is focused on two components. First, the metabolic disposition and biological activity of oxidized derivatives of linoleic acid is being actively investigated. The major pathway for oxygenation of linoleic acid involves production of 13-hydroperoxyoctadecadienoic acid by the action of lipoxygenases or cyclooxygenases. This is followed by reduction of the hydroperoxy fatty acid to the hydroxy derivative (13-HODE) and the subsequent dehydrogenation of 13-HODE to the 2,4-dienone 13-OXO. Research efforts are currently focused in two areas related to this metabolic pathway. One area of emphasis involves unraveling the biochemical contribution of 13-HODE dehydrogenase to cellular regulation. A second area of interest involves identification of crucial cellular targets interacting with key metabolites of oxidized linoleic acid. Both chemical and biochemical techniques are employed to address these questions and elucidate these pathways.
A second major area of interest involves attempts to elucidate the mechanism by which conjugated derivatives of linoleic acid, known as CLAs, inhibit mammary tumorigenesis. The CLAs have been shown to be non-toxic inhibitors of both initiation and post initiation events during mammary carcinogenesis. The emphasis in these investigations involves an examination of the potential modulation of the oxidative metabolism of polyunsaturated fatty acids by CLA. Again, identification of biological targets and the elucidation of metabolic pathways available to CLA are major goals of these NIH-supported investigations. |
Involvement of p59fyn in XEphA4 signaling  Eph class receptors are cell surface proteins that, when activated by their ligands, cause cell-cell repulsion, which is used to limit cellular interactions, thus aiding in a variety of processes, such as tissue formation and guidance of migrating cells. Activation of one member of this family in Xenopus laevis, XEphA4, leads to reorganization of the actin cytoskeleton via a mechanism involving inhibition of the small GTPase XRhoA. The rest of the biochemical pathway by which XEphA4 mediates its effects is largely unknown. This project will test the hypothesis that the tyrosine kinase Fyn (a member of the Src family of non-receptor tyrosine kinases) is involved in signaling by XEphA4. The hypothesis will be tested using a Xenopus laevis embryo assay system. This system allows expression and activation of XEphA4 in early frog embryos (at a time when the receptor would not normally be expressed), which results in loss of cell adhesion, change in cell shape, and loss of cell polarity by epithelial cells. Candidate molecules in the signaling pathway, such as Fyn in the current project, can be tested by expressing mutant forms of the candidate molecule alone or in conjunction with XEphA4 and assessing the effect on embryo phenotype. The hypothesis will be tested using experimental approaches that comprise four objectives, each of which tests a prediction based on the hypothesis. Objective 1 will test whether constitutively-active Fyn can recreate the XEphA4 phenotype. Objective 2 will determine whether inhibition of Fyn prevents the phenotypic effects of XEphA4. Objective 3 will test whether constitutive activity of XRhoA can prevent the effects of active Fyn. Objective 4 will assay for changes in Fyn activity levels in response to XEPhA4 activity. This project should add greatly to understanding of Eph receptor signaling, and will have broader impact through training of graduate and undergraduate students, including pre-service secondary-level biology teachers, and through outreach programs to local secondary schools. |
C-3'-Nucleic Acid Radicals: Generation and Mechanistic Investigations Oxidative processes are at the heart of numerous chemical and biochemical processes, including the damage of nucleic acids by ionizing radiation or specific drug interactions. This project involves the synthesis of modified nucleosides and nucleotides that will permit the elucidation of the mechanism of degradation of C-3' nucleotide radicals in DNA and RNA. Modifed nucleosides containing photoactive functional groups will be synthesized and incorporated into small DNAs and RNAs designed for the investigation of damage events. The nature and fate of nucleoside radicals derived from these site-specifically functionalized nucleic acid systems will be explored by a variety of chemical, analytical, and biophysical methods. A curriculum for a Master of Science degree will be developed, targeting specific groups in an effort to increase the pool of underrepresented minorities in the chemical workforce. This program specifically targets students who are ill prepared for graduate studies or who have not been successful in previous attempts to receive a graduate degree due to a lack of proper preparation.
Professor Amanda Bryant-Friedrich, of the Department of Chemistry at Oakland University, is developing an understanding of the chemical processes which result in the damage of DNA and RNA. Radiation, drug interactions, and other oxidative processes can lead to the formation of nucleic acid radicals. Through the synthesis and manipulation of modified nucleic acid subunits, Professor Bryant-Friedrich is elucidating the mechanisms by which these radicals lead to nucleic acid degradation. Professor Bryant-Friedrich is also working toward increasing the representation of women and minorities in the chemical workforce. Through development of a Master of Science program at Oakland University, Professor Bryant-Friedrich will provide a program targeting students who are academically ill-prepared for graduate study, placing them on track for employment or for placement in competitive doctoral programs. |
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