David Gailani, M.D.
Professor of Pathology and Medicine
Contact Information
Vanderbilt
Dept. of Pathology
Mailing Address:
Hematology/Oncology Division
538
Phone: (615) 936-1505
Fax: (615) 343-8420
E-mail: dave.gailani@vanderbilt.edu
Disease Interests
Disorders of hemostasis and thrombosis. As a clinical pathologist and a clinical hematologist, I am interested in congenital and acquired abnormalities of blood coagulation that contribute to bleeding and thrombotic disorders.
Research Specialty
Biochemistry and pathophysiology of blood coagulation The goal of the work in my laboratory is to improve our understanding of the biochemical reactions that occur during formation of a normal blood clot in response to blood vessel injury (hemostasis), and the processes that contribute to abnormal clot formation (thrombosis) in pathologic processes such as myocardial infraction, stroke, deep venous thrombosis, and disseminated intravascular coagulation. We are particularly interested in determining the importance of a group of plasma proteases called intrinsic pathway proteases (blood coagulation factors IX, XI and XII) to thrombotic disease. Recent studies from our laboratory indicate that intrinsic pathway proteases make a substantially greater contribution to pathologic thrombosis than to normal hemostasis. This has spurred an interest in targeting these proteases with therapeutic agents to control abnormal clot formation and reduce the risk of associated life-threatening consequences.
There are three areas of emphasis in the laboratory. The first concentrates on the biochemistry of the plasma proteases of the intrinsic pathway, and involves basic protein chemistry in purified systems, enzymology, and structure function analysis using recombinant proteins. The goal of the second area of emphasis is to understand how these proteases interact with other components of the hemostatic system (blood platelets and the blood vessel wall). Through this work, we hope to identify normal and abnormal triggers for coagulation that may be of clinical importance. Finally, we are taking the lessons learned from these in vitro systems to animal models of abnormal bleeding and thrombosis, with the objective of identifying pathways that can be targeted for therapeutic benefit. This work currently involves a variety of gene-deleted mice, and is being expanded to include work in primate models.
Clinical Research Description
Identification of mutations in congenital plasma coagulation factor deficiencies. As an extension of the basic science work in my research laboratory, we are interested in identifying mutations in the genes for coagulation factor XI and the related protease prekallikrein that result in congenital deficiency of these proteins. Through studying these mutations, we gain information not only on the congenital deficiency states, but also on the chemistry of the proteins involved.
Clinical Interests
Diagnosis and treatment of bleeding and thrombotic disorders. I am the medical director of the clinical coagulation laboratory at
Publications (since 1991)
Gailani D, Renné T, Gruber A: Contact Pathways and Targets for New Anticoagulants, in New Therapeutic Agents in Thrombosis and Thrombolysis. Freedman JE, Loscalzo J, Eds. Informa Healthcare,
Tucker EI, Marzec UM, Hurst S, McCarty OJT, Rugonyi S, Gailani D, Gruber A, Hanson SR: Prevention of vascular graft occlusion and thrombus-associated thrombin generation by inhibition of factor XI. Blood (In Press).
Ponczek MB, Gailani D, Doolittle RF: Evolution of the contact phase of vertebrate blood coagulation. J. Thromb. Haemost. 2008;6:1876-1883.
Cheng Q, Kantz J, Poffenberger GL, Powers AC, Gailani D: Extrahepatic expression of coagulation factor XI in humans. Thromb. Haemost. 2008;100:158-160.
Tucker EI, Gailani D, Hurst S, Cheng Q, Hanson SR, Gruber A: Survival advantage of coagulation factor XI deficient mice in peritoneal sepsis. J. Infect. Dis. 2008;198:271-274.
Smith SB, Verhamme IM, Sun M-F, Bock PE, Gailani D. Characterization of novel forms of coagulation factor XIa: Independence of factor XIa subunits in factor IX activation. J. Biol. Chem. 2008;283:6696-6705.
Schmidt AE, Sun M-F, Ogawa T, Baja SP, Gailani D: Functional role of residue 193 (chymotrypsin numbering) in serine proteases: Influence of side chain length and b-branching on the catalytic activity of blood coagulation factor XIa Biochemistry 2008;47:1326-1335.
Gailani D, Neff AT: Rare clotting factor deficiencies, in Hematology: Basic Principles and Practice. Hoffman R, Benz E, Shattil S, Furie B, Heslop H, Silberstein L, McGlave P, Eds. Churchill Livingstone, NY, NY, Fifth Edition, 2008.
Smith SB, Gailani D: Update on the physiology and pathology of factor IX activation by factor XIa. Expert Review of Hematology 2008;1:87-98.
Gailani D, Renné T: Intrinsic pathway proteases in arterial thrombosis. Arterio. Thromb. Vasc. Bio. 2007;27:2507-2513.
Gailani D, Schmidt AE, Sun, M-F, Bolton Maggs P, Bajaj SP: A cross-reactive material positive variant of coagulation factor XI (FXIP520L) with a catalytic defect. J. Thromb. Haemost. 2007; 5:781-787.
Anderson PJ, Gailani D, Feys H, Gao W, Majerus EM, Deckyman H, Sadler JE. Factor XI/ADAMTS13 complexes are quantitatively insignificant in human plasma. Haematologica 2007;92:1419-1422.
Gailani D, Renné T: The intrinsic pathway of coagulation: a target for treating thromboembolic disease? J. Thromb. Haemost. 2007;5:1106-1112.
Renné T, Gailani D: The role of factor XII in hemostasis and thrombosis: Clinical Implications. Expert Rev. Cardiovasc. Therapy 2007;5:733-741.
Renné T, Nieswandt B, Gailani D: The intrinsic pathway of coagulation is essential for thrombus stability in mice. Blood Cells, Molecules and Diseases 2006;36:148-151.
Kleinschnitz C, Stoll G, Bendszus M, Schuh K, Ulrich P, Burfeind P, Gailani, D, Nieswandt B, Renné T: Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J. Exp. Med. 2006;203:513-518.
Donahue BS, Gailani D, Mast A: Disposition of tissue factor pathway inhibitor during cardiopulmonary bypass. J. Thromb. Haemost. 2006;4:1011-1016.
Rezaie A, Sun, M-F, Gailani D: Contributions of basic amino acids in the autolysis loop of factor XIa to serpin specificity Biochemistry 2006;45:9427-9423.
Wang X, Smith PL, Hsu M-Y, Gailani D, Schumacher WA, Ogletree ML, and Seiffert DA: Effects of factor XI deficiency on ferric chloride-induced vena cava thrombosis in mice J. Thromb. Haemost. 2006;4:1982-1988.
Wang X, Cheng Q, Xu L, Feuerstein GZ, Hsu M-Y, Smith PL, Seiffert DA, Schumacher WA, Ogletree ML, Gailani D: Effects of factor IX or factor XI deficiency on ferric chloride-induced carotid artery occlusion in mice. J. Thromb. Haemost. 2005;3:695-702.
Kravtsov DV, Monahan PE, Gailani D: A classification system for cross-reactive material negative factor XI deficiency. Blood 2005;105:4671-4673.
Ogawa T, Verhamme IM, Sun M-F, Bock PE, Gailani D: Exosite-mediated substrate recognition of factor IX by factor XIa: The factor XIa heavy chain is required for initial recognition of factor IX. J. Biol. Chem. 2005;280:23523-23530.
Renné T, Pozgajová M, Grüner S, Schuh K, Pauer H, Burfeind P, Gailani D, Nieswandt B: Defective thrombus formation in mice lacking coagulation factor XII. J. Exp. Med. 2005;202:271-281.
Cheng Q, Zhao Y, Lawson WE, Polosukhin VV, Johnson JE, Blackwell TS, Gailani D: The effects of intrinsic pathway protease deficiencies on plasminogen deficient mice. Blood 2005;106:3055-3057.
Walsh PN, Gailani D: Factor XI, in Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Colman RW, Hirsch J, Marder VJ, Clowes AW, George JN, Eds. Lipincott Williams & Wilkins,
Kravtsov DV, Wu W, Meijers, JCM, Sun M-F, Blinder M, Dang TP, Wang W, Gailani D: Dominant factor XI deficiency caused by mutations in the factor XI catalytic domain. Blood 2004;104:128-134.
Schmidt AE, Ogawa T, Gailani D, Bajaj SP: Structural role of Gly193 in serine proteases: Investigations of a Gly555Glu (Gly193 in chymotrypsin) mutant of blood coagulation factor XI. J. Biol. Chem. 2004;279:29485-29492.
Zivelin A, Ogawa T, Rosenberg N, Bulvik S, Landau M, Abboud M, Toomey JR, Lane J, Seligsohn U, Gailani D: Severe factor XI deficiency caused by a Gly555 to Glu mutation (Factor XI-Glu555): A cross-reactive material positive variant defective in factor IX activation. J. Thromb. Haemost. 2004;2:1782-1789.
Baglia FA, Gailani D, Lopez JA, Walsh PN: Identification of a binding site for glycoprotein Iba in the apple 3 domain of factor XI. J. Biol. Chem. 2004;279:45470.
Gailani D, Zivelin A, Sinha D Walsh PN: Do platelets synthesize factor XI? J. Thromb. Haemost. 2004;2:1709-1712.
Donahue BS, Gailani D, Higgins MS, Drinkwater DC, George, AL: Factor V
Aktimur A, Gabriel MA, Gailani D, Toomey JR: The factor IX g-carboxyglutamic acid (Gla) domain is involved in interactions between factor IX and factor XIa. J. Biol. Chem. 2003;278:7981-7987.
Tarumi T, Kravtsov D, Moore J, Williams SM Gailani D: Common single nucleotide polymorphisms (SNPs) in the promoter region of the human factor XI gene. J. Thromb.. Haemost. 2003;1:1854-1856.
Cheng Q, Sun M-F, Aktimur A, Kravtsov D, Gailani D: Factor XI apple domains and protein dimerization. J. Thromb. Haemost. 2003;1:2340-2347.
Donahue BS, Byrne DW, Gailani D, George
Renné T, Gailani D, Meijers JCM, Müller-Esterl W: Characterization of the H-kininogen binding site on factor XI: a comparison of factor XI and plasma prekallikrein. J. Bio. Chem. 2002;277:4892-4899.
Rosen ED, Gailani D, Castellino FJ: Factor XI is essential for thrombus formation following FeCl3-induced injury of the carotid artery in the mouse. Thromb. Haemost. 2002;87:774-776.
Tarumi T, Kravtsov D, Zhao M, Williams SM, Gailani D: Cloning and characterization of the human factor XI gene promoter: A critical role for transcription factor HNF-4a in hepatocyte specific expression of factor XI. J. Biol. Chem. 2002;277:18510-18516.
Sinha D, Marcinkiewicz M, Gailani D, Walsh PN: Molecular cloning and biochemical characterization of rabbit factor XI. Biochem. J. 2002;367:49-56.
Renné T, Sugiyama A, Gailani D, Jahnen-Dechent W, Walter U, Müller-Esterl W: Fine mapping of the H-kininogen binding site in plasma prekallikrein apple domain 2. Int. Immunopharmacol. 2002;2:1867-1873.
Gailani D, Broze GJ: Factor XI and the contact system, in Metabolic and Molecular Bases of Inherited Disease. Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B, Eds. McGraw-Hill, NY, NY, 2001.
Gailani D: Gene targeting in hemostasis: Factor XI. Frontiers in Bioscience 2001;6:200-207.
Chan JCY, Ganopolsky JG, Cornelissen I, Suckow MA, Sandoval-Cooper MJ, Brown EC, Noria F, Gailani D, Rosen ED, Ploplis VA, Castellino F: The characterization of mice with a targeted combined deficiency of protein C and factor XI. Am. J. Path. 2001;158:469-479.
Gailani D, Ho D, Sun M-F, Cheng Q, Walsh PN: Model for a factor IX activation complex on blood platelets: dimeric conformation of factor XIa is essential. Blood 2001;97:3117-3122.
Sun M-F, Baglia FA, Ho D, Martincic D, Ware RE, Walsh PN, Gailani D: Defective binding of factor XI-N248 to activated human platelets. Blood 2001;98:125-129.
Barrow RT, Healey JF, Gailani D, Scandella D, Lollar P: Reduction of the antigenicity of factor VIII toward complex inhibitory antibody plasmas using multiply-substituted hybrid human/porcine factor VIII molecules. Blood 2000;95:564-568.
Tarumi T, Martincic D, Thomas A, Janco R, Hudson M, Baxter P, Gailani D: Familial thrombophilia associated with fibrinogen
Ho DH, Badellino K, Baglia FA, Sun M-F, Zhao M, Gailani D, Walsh PN: The role of high molecular weight kininogen and prothrombin as cofactors in the binding of factor XI A3 domain to the platelet surface. J. Biol. Chem. 2000;275:25139-25145.
Tarumi T, Martincic D, Whitlock JA, Addy JH, Williams SM, Gailani D: Conserved worldwide linkage disequilibrium in the human factor XI gene. Genomics 2000;70:269-272.
Gailani D: Activation of factor IX by factor XIa. Trends Cardiovasc. Med. 2000;10:198-204.
Gailani D, Reese EP: Anticoagulant induced skin necrosis in a patient with hereditary deficiency of protein S. Am. J. Hematol. 1999;60:231-236.
Martincic D, Kravtsov V, Gailani D: Factor XI mRNA in human platelets. Blood 1999;94:3397-3404.
Sun M-F, Zhao M, Gailani D: Identification of amino acids in the factor XI apple three domain required for activation of factor IX. J. Biol. Chem. 1999;274:36373-36378.
Martincic D, Zimmerman SA, Ware RE, Sun M, Whitlock, JA, Gailani D: Identification of mutations and polymorphisms in the factor XI gene of an African-American family by dideoxyfingerprinting. Blood 1998;92:3309-3317.
Zhao M, Abdel-Razek T, Sun M-F, Gailani D: Characterization of a heparin binding site on factor XI. J. Biol. Chem. 1998;273:31153-31159.
Gailani D, Lasky N, Broze GJ: A murine model of factor XI deficiency. Blood Coag. Fibrinol. 1997;8:134-144.
Gailani D, Broze GJ: Regulation of coagulation by tissue factor pathway inhibitor, in Recent Advances in Blood Coagulation 7, Poller L, Ludlum CA, Eds., pp. 1-17 Churchill Livingstone, Edinburgh, 1997.
Gailani D, Sun M-F, Sun Y: A comparison of murine and human factor XI. Blood 1997;90:1055-1065.
Sun Y, Gailani D: Identification of a factor IX binding site on the third apple domain of activated factor XI. J. Biol. Chem. 1996;271:29023-29028.
Gailani D: Advances and dilemmas in factor XI. Current Opin. Hematol. 1994;1:347-353.
Girard TJ, Gailani D, Broze GJ: Complementary DNA sequencing of canine tissue factor pathway inhibitor reveals a unique nanomeric repetitive sequence between the second and third Kunitz domains. Biochem. J. 1994;303:923-928.
Gailani D, Broze GJ: Effects of glycosaminoglycans on factor XI activation by thrombin. Blood Coagulation and Fibrinolysis 1993;4:15-20.
Broze GJ, Gailani D: The role of factor XI in coagulation. Thromb. Haemost. 1993;70:72-74.
Gailani D, Broze GJ: Factor XII-independent activation of factor XI in plasma: effects of sulfatides on tissue factor induced coagulation. Blood 1993;82:813-819. Gailani D, Broze GJ: Factor XI activation by thrombin and factor XIa. Sem. Thromb. Hemostasis 1993;19:396-404.
Gailani D: An IgG inhibitor to coagulation factor XIII—termination of bleeding using staphylococcal protein A plasmapheresis. Am. J. Med. 1992;92: 110-112.
Gailani D, Broze GJ: Factor XI activation in a revised model of blood coagulation. Science 1991;253:909-912.
