个人简介

2006-present Adjunct Professor of Biochemistry & Molecular Biology, Indiana University School of Medicine 1996-present Director, WM Keck Center for Transgene Research, University of Notre Dame 1983-present Kleiderer/Pezold Professor of Biochemistry, University of Notre Dame 1979-2002 Dean, College of Science, University of Notre Dame 1977-1983 Professor, University of Notre Dame 1974-1977 Associate Professor, University of Notre Dame 1970-1974 Assistant Professor, University of Notre Dame 1968-1970 NIH Postdoctoral Fellow, Duke University 1968 Ph.D. in Biochemistry, University of Iowa 1964 B.S. University of Scranton Award: 2008 Wyeth-ISPF Research Prize 2006 Fellow of the Reilly Center for Science, Technology, and Values 2003 Annual Faculty Award, University of Notre Dame 2001 Elected Fellow of the American Heart Association and the Council on Arteriosclerosis, Thrombosis, and Vascular Biology

研究领域

Biochemistry

The interests of Professor Castellino's laboratory involve the structure, function and activation of proteins that participate in blood coagulation and blood clot dissolution. The in vivo mechanisms of the roles of these proteins in these processes are being addressed through in vivo targeted gene-replacement approaches and corresponding in vitro structure-function studies on these genes and proteins are being studied by the most modern biophysical techniques, e.g., X-ray crystallography, NMR, etc. Most of these proteins exist in an inactive state in plasma and thus must be activated to enzymes to exhibit their functional properties. The molecular events involved in the activation and analysis of the concomitant structural changes that occur in the protein are investigated by modern biochemical techniques. Major tools of the laboratory involve cloning, mutagenesis and expression of variant recombinant proteins and individual protein domains, immunochemical studies of the proteins, as well as physical and chemical analysis of their solution structures. The properties of the proteins are then related to their functions. Another project receiving attention involves the structure-function relationships of small gamma-carboxyglutamic acid (Gla)-containing peptides from marine cone snails that target the brain NMDA receptor. These peptides inhibit the flow of calcium into neuronal cells, this latter event being responsible for the neuropathology associated with stroke, epilepsy, Alzheimer's Disease, ALS, etc. The biochemical, pharmacological and neurobiological mechanisms of the actions of these peptides are under study. Peptide synthesis, receptor binding, molecular biological and electrophysiological tools are currently employed in this work. To determine the biological functions of genes encoding coagulation and clot-dissolving proteins in hemostasis, cancer, inflammation, wound healing, embryonic implantation and development, metastases, and athersclerosis, gene deletion and other gene targeting experiments are being performed in mice, in conjunction with phenotyping of these animals. Such studies are expected to provide important information on the development and progression of these disease states.

近期论文

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Bao, Y.J.; Liang, Z.; Booyjzsen, C.; Mayfield, J.A.; Li, Y.; Lee, S.W.; Ploplis, V.A.; Song, H.; Castellino, F.J. "Unique Genomic Arrangements in an Invasive Serotype M23 Strain of Streptococcus pyogenes Identify Genes That Induce Hypervirulence." J. Bacteriol. 2014, 196 (23), 4089-4102. Huang, L.X.; Balsara, R.D.; Castellino, F.J. "Synthetic Conantokin Peptides Potently Inhibit N-methyl-D-aspartate Receptor-Mediated Currents of Retinal Ganglion Cells." J. Neurosci. Res. 2014, 92 (12), 1767-1774. Ploplis, V.A.; Donahue, D.L.; Sandoval-Cooper, M.J.; MorenoCaffaro, M.; Sheets, P.; Thomas, S.G.; Walsh, M.; Castellino, F.J. "Systemic Platelet Dysfunction Is the Result of Local Dysregulated Coagulation and Platelet Activation in the Brain in a Rat Model of Isolated Traumatic Brain Injury." J. Neurotram. 2014, 31 (19), 1672-1675. Bhattacharya, S.; Liang, Z.; Quek, A.J.; Ploplis, V.A.; Law, R.; Castellino, F.J. "Dimerization Is Not a Determining Factor for Functional High Affinity Human Plasminogen Binding by the Group A Streptococcal Virulence Factor PAM and Is Mediated by Specific Residues within the PAM a1a2 Domain." J. Biol. Chem. 2014, 289 (31), 21684-21693. Mayfield, J.A.; Liang, Z.; Agrahari, G.; Lee, S.W.; Donahue, D.L.; Ploplis, V.A.; Castellino, F.J. "Mutations in the Control of Virulence Sensor Gene from Streptococcus pyogenes after Infection in Mice Lead to Clonal Bacterial Variants with Altered Gene Regulatory Activity and Virulence." PLOS One 2014, 9 (6), e100698. Walsh, M.; Ploplis, V.A.; Fritz, B.; Jbara, M.; Hurwich, M.; Evans, E.; Abernathy, M.; Miller, A.; Waxman, D.; McCurdy, M.; Castellino, F. "Successful Thromboelastographic Goal-Directed Blood Component Therapy, Prothrombin Complex Concentrate, and RFVIIA Administration Without Tranexamic Acid for Reversal of Severe Coagulopathy in an Obstetrical Patient Presenting with Hemorrhagic Cardiac Arrest." Am. J. Hematol. 2014, 89 (6), E50.