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Director, W.M. Keck Center for Transgene Research
Kleiderer-Pezold Professor of Biochemistry
Department of Chemistry and Biochemistry
Dean emeritus, College of Science
University of Notre Dame
Adjunct Professor, Department of Biochemistry and Molecular Biology
Indiana University School of Medicine, South Bend, Indiana
Education
BS, University of Scranton, 1964
MS, University of Iowa, 1966
PhD, University of Iowa, 1968
Postdoctoral fellow, Duke University, 1968-1970
Address
W. M. Keck Center for Transgene Research
230 Raclin-Carmichael Hall
University of Notre Dame
Notre Dame, IN 46556
Contact
Phone: (574) 631-8996
Fax: (574) 631-8017
E-mail: fcastell@nd.edu
Honors and Awards
1966-1968 NIH Predoctoral Fellowship
1968-1970 NIH Postdotoral Fellowship
1974-1979 NIH Research Career Development Award
1974-1979 Camille and Henry Dreyfus Teacher-Scholar Award
1982 Honorary LL.D., University of Scranton
1983 Akron section of the A.C.S. Research Award
1989 Frank O’Hara Award in Education, University of Scranton National Alumni Society
1990 Merit Award (HL-13423), NHLBI, National Institutes of Health
1992 Annual Undergraduate Lecture, University of Waterloo, Waterloo, Ontario, Canada
1994 Annual Graduate School Award, University of Notre Dame
1994 Commencement Address, University of Waterloo, Waterloo, Ontario, Canada
1994 Honorary D.Sc., University of Waterloo, Waterloo, Ontario, Canada
1995 Educator of the Year Award, Michiana Executive Journal
2003 Annual University Faculty Award, University of Notre Dame
Memberships and Committees
1982-1985 Member, NIH Biomedical Sciences Study Section
1983 Elected Fellow of the N. Y. A. S.
1988 Elected Fellow of the A. A. A. S.
1990 Member, Parent Committee on SCOR Proposals in Thrombosis (NIH)
1990-1994 Member and Chair (1990-1992), NIH Hematology 2 Study Section
2001 Elected Fellow of the American Heart Association and the Council on Thrombosis
2002 Department of Chemistry and Biochemistry Committee on Appointments and Promotions
2005 College of Science Committee on Faculty Grievance
2005 University Committee on Appeals
2005 Faculty Athletic Board
2006 Fellow of the Reilly Center for Science, Technology, and Values, University of Notre Dame
Other Activities
1996 Editorial Boards, Journal of Biological Chemistry; Biotechnology and Applied Biochemistry
1998 Editor-in-Chief, Current Drug Targets
Research Focus
The overall interests of Professor Castellino's laboratory are centered on the in vitro and in vivo relationships between hemostasis and inflammation. More specifically, the function and activation of proteins that participate in blood coagulation, anticoagulation, and blood clot dissolution are studied at the protein and gene levels using modern biochemical and biophysical techniques, e.g., cloning, mutagenesis and expression of variant recombinant proteins and individual protein domains, immunochemistry, and physical and chemical studies of their structures, employing X-ray crystallography, NMR, calorimetry. The properties of the proteins are then related to their functions. This work is then carried to the gene, cellular, and whole animal levels with the aim of understanding the cross-communications between the blood clotting system and the inflammatory response. Here, appropriate acute and chronic inflammatory disease models (e.g., sepsis/endotoxemia, atherosclerosis, asthma, cancer) are investigated in genetically-altered mice to attempt to mechanistically understand the pathophysiology of these diseases. Major tools employed in these studies include construction and utilization of in vivo gene-targeted and traditional transgenic mice, cell-specific gene microarray studies, organ- and cell-specific imaging, histology, and sophisticated mouse surgical approaches.
Another set of projects 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, and this latter event is at least in-part responsible for the neuropathologies 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 research.
Selected Recent Publications
Green KA, Almholt K, Plough M, Rono B, Castellino FJ, Johnsen M, Bugge TH, Romer J, Lund LR. (2008). Profibrinolytic effects of metalloproteinases during skin wound healing in the absence of plasminogen. J Invest Dermatol. 128:2092-2101.
Iwaki T, Ploplis VA, Castellino FJ. (2008). The hemostasis system in murine atherosclerosis. Curr Drug Targets. 9:229-238.
Fu Q, Figuera-Losada M, Ploplis VA, Cnudde S, Geiger JH, Prorok M, Castellino FJ. (2008). The lack of binding of VEK-30, an internal peptide from the group A streptococcal M-like protein, PAM, to murine plasminogen is due to two amino acid replacements in the plasminogen kringle-2 domain. J Biol Chem. 283:1580-1587.
Merkulov S, Zhang WM, Komar AA, Schmaier AH, Barnes E, Zhou Y, Lu X, Iwaki T, Castellino FJ, Luo G, McCrae KR. (2008). Deletion of urine kininogen gene 1 (mKng1) causes loss of plasma kininogen and delays thrombosis. Bood. 111:1274-1281.
Kerschen FJ, Fernandez JA, Cooley BC, Yang XV, Sood R, Mosnier LO, Castellino FJ, Mackman N, Griffin JH, Weiler H. (2007). Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C. J Exp Med. 204:2439-2448.
Bhatnager S, Shinagawa K, Castellino FJ, Schorey JS. (2007). Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood. 110:3234-3244.
Sheng Z, Dai Q, Prorok M, Castellino FJ. (2007). Subtype-selective antagonism of N-methyl-d-aspartate receptor ion channels by synthetic conantokin peptides. Neuropharmacology. 53:145-156.
Iwaki T, Donahue D, Castellino FJ (2007). High levels of LDL-cholesterol rescue the neonatal mortality associated with afibrinogenemia in mice. J Thromb Haemost 3:624-626.
Cnudde SE, Prorok M, Castellino FJ, Geiger JH (2007). The crystal structures of the calcium-bound con-G and con-T[K7g] dimeric peptides demonstrate a novel metal-dependent helix forming motif. J Am Chem Soc 129:1586-1593.
Lay AJ, Donahue DL, Tsai M-J, Castellino FJ (2007). Acute inflammation is exacerbated in mice genetically predisposed to a severe Protein C deficiency. Blood 109:1984-1991.
Shinagawa K, Martin AJ, Ploplis VA, Castellino FJ (2007). Coagulation Factor Xa modulates airway remodeling in a mouse model of asthma. Am J Resp Crit Care Med 175:136-143.
Iwaki T, Sandoval-Cooper MJ, Brechmann M, Ploplis VA, Castellino FJ (2006). A fibrinogen deficiency accelerates the initiation of LDL-cholesterol-driven atherosclerosis via thrombin generation and platelet activation in genetically-predisposed mice. Blood 107:3883-3891.
Cruz-Topete D, Iwaki T, Ploplis VA, Castellino FJ (2006). Delayed inflammatory responses to lethal endotoxemia in fibrinogen-deficient mice. J Pathol 210:325-333.
Xu H, Ploplis VA, Castellino FJ (2006). A coagulation Factor VII deficiency protects against acute inflammatory responses in mice. J Pathol 210:488-496.
Castellino FJ, Ganopolsky JG, Noria F, Sandoval-Cooper MJ, Ploplis VA (2006). Focal arterial inflammation is augmented in mice with a deficiency of the Protein C gene. Thromb Haemost 97:794-801.
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