Francis J. Castellino

Francis J. Castellino

In Vitro and In Vivo Relationships between Hemostasis and Inflammation

Biography

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

Selected Awards

2014
University of Iowa Carver College of Medicine Distinguished Alumnus 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
1998
Fellow, American Association for the Advancement of Science

Research Interests

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.

Recent Papers

  • Stroo, I.; Zeerleder, S.; Ding, C.; Luken, B. M.; Roelofs, J. J. T. H.; de Boers, O. J.; Meijers, J. C. M.; Castellino, F. J.; van 't Veer, C.; van der Poll, T. "Coagulation factor XI improves host defence during murine pneumonia-derived sepsis independent of factor XII activation." Thromb. Haemostasis 2017, 117, 1601-1614.
  • Bao, Y.; Li, Y.; Liang, Z.; Agrahari, G.; Lee, S. W.; Ploplis, V. A.; Castellino, F. J. "Comparative pathogenomic characterization of a non-invasive serotype M71 strain Streptococcus pyogenes NS53 reveals incongruent phenotypic implications from distinct genotypic markers." Pathog. Dis. 2017, 75, ftx056.
  • Glinton, K.; Beck, J.; Liang, Z.; Qiu, C.; Lee, S. W.; Ploplis, V. A.; Castellino, F. J. "Variable region in streptococcal M-proteins provides stable binding with host fibrinogen for plasminogen-mediated bacterial invasion." J. Biol. Chem. 2017, 292, 6775-6785.
  • Gupta, K. K.; Donahue, D. L.; Sandoval-Cooper, M. J.; Castellino, F. J.; Ploplis, V. A. "Plasminogen Activator Inhibitor-1 Protects Mice Against Cardiac Fibrosis by Inhibiting Urokinase-type Plasminogen Activator-mediated Plasminogen Activation." Sci. Rep. 2017, 7, 365.
  • Stroo, I.; Yang, J.; de Boer, J. D.; Roelofs, J. J. T. H.; van 't Veer, C.; Castellino, F. J.; Zeerleder, S.; van der Poll, T. "Factor XI deficiency enhances the pulmonary allergic response to house dust mite in mice independent of factor XII." Am. J. Physiol.-Lung C. 2017, 312, L163-L171.
  • Yuan, Y.; Balsara, R. D.; Zajicek, J.; Kunda, S.; Castellino, F. J. "Discerning the Role of the Hydroxyproline Residue in the Structure of Conantokin RI-B and Its Role in GluN2B Subunit-Selective Antagonistic Activity toward N-Methyl-D-Aspartate Receptors." Biochemistry 2016, 55, 7112-7122.

Contact Information

  • Kleiderer-Pezold Professor of Biochemistry; Director, WM Keck Center for Transgene Research
  • Office: 230 Raclin-Carmichael Hall
  • Phone: 574-631-9152
  • Send an email
  • Visit Website

Primary Research Areas

Research Specialties