Department of Chemistry & Biochemistry

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

2020

ISTH Esteemed Career Award

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 Publications

• Silva, L. M.; Doyle, A. D.; Greenwell-Wild, T.; Dutzan, N.; Tran, C. L.; Abusleme, L.; Juang, L. J.; Leung, J.; Chun, E. M.; Lum, A. G.; Agler, C. S.; Zuazo, C. E.; Sibree, M.; Jani, P.; Kram, V.; Martin, D.; Moss, K.; Lionakis, M. S.; Castellino, F. J.; Kastrup, C. J.; Flick, M. J.; Divaris, K.; Bugge, T. H. and Moutsopoulos, N. M. "Fibrin is a Critical Regulator of Neutrophil Effector Function at the Oral Mucosal Barrier" 2021 Science, 374 (6575), pp.1575. DOI: 10.1126/science.abl5450.
• Iwaki, T.; Arakawa, T.; Sandoval-Cooper, M. J.; Smith, D. L.; Donahue, D.; Ploplis, V. A.; Umemura, K. and Castellino, F. J. "Plasminogen Deficiency significantly Reduces Vascular Wall Disease in a Murine Model of Type IIa Hypercholesterolemia" 2021 Biomedicines, 9 (12), 1832. DOI: 10.3390/biomedicines9121832.
• Ayinuola, O.; Ayinuola, Y. A.; Qiu, C. J.; Lee, S. W.; Ploplis, V. A. and Castellino, F. J. "Binding of the Kringle-2 Domain of Human Plasminogen to Streptococcal PAM-Type M-Protein Causes Dissociation of PAM Dimers" 2021 Microbiologyopen, 10 (6), e1252. DOI: 10.1002/mbo3.1252.
• Vu, H. M.; Hammers, D. E.; Liang, Z.; Nguyen, G. L.; Benz, M. E.; Moran, T. E.; Higashi, D. L.; Park, C. J.; Ayinuola, Y. A.; Donahue, D. L.; Flores-Mireles, A. L.; Ploplis, V. A.; Castellino, F. J. and Lee, S. W. "Group A Streptococcus-Induced Activation of Human Plasminogen is Required for Keratinocyte Wound Retraction and Rapid Clot Dissolution" 2021 Frontiers in Cardiovascular Medicine, 8, 667554. DOI: 10.3389/fcvm.2021.667554.
• Ito, T.; Suzuki, Y.; Sano, H.; Honkura, N.; Castellino, F. J. and Urano, T. "Demonstration of Three Distinct High-Molecular-Weight Complexes between Plasminogen Activator Inhibitor Type 1 and Tissue-Type Plasminogen Activator" 2022 Thrombosis and Haemostasis, 122 (03), pp.336-343. DOI: 10.1055/a-1508-7919.
• Ayinuola, Y. A.; Brito-Robinson, T.; Ayinuola, O.; Beck, J. E.; Cruz-Topete, D.; Lee, S. W.; Ploplis, V. A. and Castellino, F. J. "Streptococcus Co-Opts a Conformational Lock in Human Plasminogen to Facilitate Streptokinase Cleavage and Bacterial Virulence" 2021 Journal of Biological Chemistry, 296, 100099. DOI: 10.1074/jbc.RA120.016262.