The Inaugural Doisy Conference on Coagulation (DCC) will take place on Monday, May 5, 2025, at the Missouri Botanical Garden Bayer Event Center located at 4344 Shaw Blvd., St. Louis, MO.

The DCC is a one-day event for researchers and trainees in the biomedical sciences.

The registration deadline was Friday, April 11, 2025.

Questions? Contact Samantha Deavila (Email)

Conference Organizers:
Enrico Di Cera, M.D., and Rodney Camire, Ph.D.

8:00 – 8:30 am:

8:30 – 9:00 am:

“Molecular mechanism of vitamin K-dependent γ-carboxylation at the membrane interface”

1. Discuss how the integral membrane vitamin K-dependent γ-carboxylase recognizes vitamin K-dependent proteins and catalyzes processive carboxylation of multiple glutamate residues.
2. Describe how vitamin K-dependent γ-carboxylase generates free hydroxide ion as an exceptionally strong base required to deprotonate the γ-carbon of glutamates.
3. Explain how vitamin K-dependent γ-carboxylase resolves the challenge of coupling of KH₂ epoxidation to γ-carboxylation across the membrane interface.

9:00 – 9:30 am:

“Structural analysis of the activation and inhibition of the intrinsic tenase complex”

1. Discuss how the coagulation factors VIII (fVIII) and IX (fIX) form the intrinsic tenase complex following activation on the surface of activated platelets, resulting in the calcium-dependent proteolytic activation of factor X to Xa.
2. Describe the structural basis of fVIII inhibition by the pathogenic antibody response to hemophilia A replacement therapy, which occurs in 30% of hemophilia A patients who have received repeated infusions.
3. Present the first experimental data describing the 3D structure of the tenase complex between activated fVIII (fVIIIa) and fIX (fIXa), along with conformational changes that occur during fVIIIa A2 domain dissociation.

9:30 – 10:00 am:

“Structural basis of prothrombin recognition by anti-prothrombin antiphospholipid antibodies: Friends or foes?”

1. Explore autoantibody heterogeneity in Antiphospholipid Syndrome.
2. Introduce a novel classification of antiphospholipid anti-prothrombin antibodies based on their mode of antigen recognition.
3. Explain how antiphospholipid anti-prothrombin antibodies cause lupus anticoagulant.
4. Discuss contexts where antiphospholipid anti-prothrombin antibodies may be pathogenic or protective.

10:00 – 10:30 am:

“Arginine methylation by protein arginine methyltransferase (PRMT1) affects ADAMTS13 secretion and function”

1. Describe the role of ADAMTS13 in pathogenesis of thrombotic thrombocytopenic purpura.
2. Focus on the role of protein arginine methylation in regulation of ADAMTS13 function.
3. Describe the potential therapeutic implications of ADAMTS13 variants for TTP and other thrombotic disorders.

10:30 – 10:45 am:

10:45 – 11:15 am:

“Investigating structural features that control factor XIII substrate specificity”

11:15 – 11:45 am:

“Venous thrombosis and factor XIII: Linking biochemical mechanisms to novel therapeutic strategies”

1. Describe the roles of fibrinogen, factor XIII, and fibrin crosslinking in venous thrombosis/thromboembolism.
2. Explore newly recognized factor XIII biology, including persistent gaps in the knowledgebase.
3. Discuss potential therapeutic implications of targeting factor XIII(a) in venous thrombosis/thromboembolism.

11:45 am – 12:15 pm:

“Molecular structural basis of blood clot mechanical properties: Unfolding of fibrin and rupture/embolization”

1. Describe the mechanical properties of clots and their essential role in hemostasis and thrombosis.
2. Explore how fibrin forms the structural scaffold of blood clots and thrombi that is the basis of their mechanical properties.
3. Discuss how the molecular unfolding of fibrin from forces in the vasculature is an important element of the mechanical properties of fibrin.
4. Explain how the rupture mechanics of fibrin clots provides a foundation for understanding thrombotic embolization.

12:15 – 1:15 pm:

1:15 – 1:45 pm:

“Analysis of factor V and factor V-short anticoagulant function”

1. Describe how factor V has both pro- and anticoagulant properties. As an anticoagulant, it functions as a cofactor for TFPIa/PS and for APC/PS. In addition, FV-short, a spliced isoform of FV, also acts as a cofactor for TFPIa/PS.
2. Provide an overview of FV/FV-short anticoagulant function and provide new mechanistic data especially as it relates to FV-short.
3. Discuss the in vitro and in vivo consequences of altering FV’s anticoagulation function using novel monoclonal antibodies.

1:45 – 2:15 pm:

“Structural basis for the inactivation of FVa by activated protein C”

1. Describe how activated protein C (APC) down-regulates the coagulation process.
2. Explore the structural definition of APC cleavage sites on activated factor V (FVa) and APC protease domain surface loops.
3. Discuss the cryogenic electron microscopy (cryo-EM) structure of the complex FVa bound to APC and the mechanism by which cleavage sites of FVa engage APC.

2:15 – 2:45 pm:

“Effects of TFPI and activated protein C on developmental angiogenesis in the brain”

1. Describe how cerebrovascular angiogenesis is disrupted by excess thrombin production in embryos lacking TFPI.
2. Describe how altering FV, either through genetic deletion or overexpression of aPC, modifies developmental angiogenesis in the brain of mice lacking TFPI.

2:45 – 3:15 pm:

“Protein S: A potential adjunct therapy for hemophilia B”

1. Explain the inhibitory role of Protein S on Factor IXa, highlighting its importance in modulating thrombin generation and maintaining hemostatic balance.
2. Identify the specific amino acid residues in Factor IXa that mediate its interaction with Protein S.
3. Introduce anti–Protein S antibodies as potential therapeutic adjuncts in Hemophilia B, capable of enhancing Factor IXa activity by neutralizing endogenous Protein S.
4. Explore the therapeutic potential of Protein S–binding aptamers as a strategy to modulate its inhibitory effect on Factor IXa, offering a novel approach to enhance coagulation in Hemophilia B.

3:15 – 3:30 pm:

3:30 – 4:00 pm:

“Contact factor structure and assembly of the contact activation system”

1. Discuss how the contact factors, factor XI (FXI) and prekallikrein (PK), reach into the intrinsic pathway of coagulation via cleavage of factor IX (FIX) and in inflammation via high-molecular weight kininogen (HK) cleavage, resulting in bradykinin (BK) generation.
2. Explore the experimentally determined 3D structures of contact factors PK and FXI, with focus on conformational changes that expose cleavage sites and exosites in FXI. PK and FXI protein-protein interactions with HK will also be discussed.
3. Explain how an improved understanding of the protein:protein interactions between these proteins provides a scaffold to develop new therapeutic opportunities to target thrombotic and inflammatory diseases.

4:00 – 4:30 pm:

“The contact pathway and endothelial cell barrier function”

1. Discuss FXI and sepsis, along with recent data on te effects of inhibiting FXIa activity in a model of live bacterial infection.
2. Discuss FXI and the endothelium, highlighting mechanistic studies of regulation of endothelial VE-cadherin levels by FXIa.
3. Describe the translation of FXI inhibitors and their use in septic patients.

4:30 – 5:00 pm:

“Factor XII and initiation of contact activation”

1. Discuss how the plasma contact protein factor XII is a key component of systems for bradykinin production (the kallikrein-kinin system) and initiation of surface-dependent coagulation.
2. Explain how dysregulation of factor XII activation or activity has been linked to thrombo-inflammatory disorders.
3. Focus on a new AI-generated model of factor XII and describe novel mechanisms that regulate conversion of factor XII to its active protease form, factor XIIa.
4. Discuss how a better understanding of the factor XII structure may facilitate development of novel therapeutic approaches for treating thrombo-inflammatory disorders.

5:00 – 8:00 pm: