Thrombosis, Hemostasis and Vascular Biology

Our laboratory has two distinct research focuses:

1. Basic science studies of hemostasis and vascular biology with a focus on the physiological function of Tissue Factor Pathway Inhibitor (TFPI)
2. Clinical and translational research studies of iron metabolism in blood donors
   
   

Basic Science Studies:

The blood vessel contains several anticoagulant proteins that prevent the formation of blood clots. The work in our laboratory is focused on one of these proteins called tissue factor pathway inhibitor (TFPI). Humans without TFPI have not been identified and genetically altered mice that do not make TFPI die during embryonic development demonstrating that TFPI has critically important physiological functions. TFPI is a serine protease inhibitor that exerts anticoagulant activity during the very early stages of blood coagulation. Our laboratory uses a wide variety of biochemical, cellular (tissue culture) and animal models to define and characterize the physiological functions of TFPI. These include studies of the biochemical mechanisms that allow TFPI to inhibit blood coagulation proteases and associate with the surface of blood vessels and platelets, characterization and functional assessment of different alternatively spliced forms of TFPI, and the development of new mouse models to examine the function of TFPI in cerebrovascular development and other functions in vivo. We also use human samples to examine how plasma TFPI is modulated in human disease. The results of these studies will shed new light on a wide range of human bleeding disorders, such as hemophilia, and diseases that are associated or caused by intravascular blood clots, such as deep venous thrombosis, heart attack, stroke, and vascular dementia.

Clinical and Translational Studies:

Blood donation removes a large amount of iron from the blood donor. Since blood donation is allowed every 56 days in the United States, repeated donation produces iron deficiency and iron deficiency anemia in many donors. Thus, blood donors are a unique population of healthy individuals for study of dietary iron absorption, hemoglobin production, and the adverse consequences of iron deficiency. We direct the Wisconsin Hub of the National Heart Lung and Blood Institute's Recipient Epidemiology and Donor Evaluation Study (REDS-IV-P). REDS-IV-P is a multi-institutional group of investigators who perform a number of studies to ensure the safety and availability of blood products in the United States.

Basic Science Grant Support:

• National Heart Lung and Blood Institute Award R01HL068835 “Characterization of an isoform specific anticoagulant function of TFPIα”  08/2002-12/2023 (Principal Investigator)
• National Heart Lung and Blood Institute Award R01HL149634 “TFPI, Protein S, and plasma FIXa in hormone-induced hypercoagulability” 07/2021-6/2025 (Principal Investigator, MPI with John Sheehan)
• Novo Nordisk Research Grant 2007-2024 (Principal Investigator)
• National Institute for Child Health and Development Award R01HD099638 “Anti-coagulation factors and placentation” 07/2019-06/2024 (Co-Investigator) 

Clinical and Translational Studies Grant Support

• National Heart Lung and Blood Institute Retroviral Epidemiology Donor Study-IV-Pediatrics (REDS-IV-P) 03/2019-02/2026 (Principal Investigator)
• National Heart Lung and Blood Institute Retroviral Epidemiology Donor Study-III (REDS-III) 03/2011-02/2020 (Principal Investigator)
• National Heart Lung and Blood Institute R01 Award “Mitigating iron deficiency in blood donors” 01/2011-12/2015 (Principal Investigator)

Daniel Bougie, PhD
Senior Research Scientist

Susan Maroney, DVM, PhD
Senior Research Scientist

Nicholas Martinez
Senior Research Technologist

Julie Peterson-Bougie, PhD
Senior Research Scientist

Amy Siebert-McKenzie
Postdoctoral Fellow

Click Here for a full list of publications from Dr. Alan Mast

Selected Publications:

1. Maroney SA, Siebert AE, Martinez ND, Rasmussen M, Peterson JA, Weiler H, Lincoln J, Mast AE: Platelet tissue factor pathway inhibitor-α dampens cardiac thrombosis and associated fibrosis in mice. J Thromb Haemost 2023 21:639-651. PMC36696221
2. Peterson JA, Gupta S, Martinez ND, Hardesty B, Maroney SA, Mast AE: Factor V east Texas variant causes bleeding in a three-generation family. J Thromb Haemost 2022, 20:565-573. PMC8885967
3. Peterson JA, Maroney SA, Martinez ND, Mast AE: A major reservoir for heparin-releasable TFPIα is extracellular matrix. Arter Thromb and Vasc Biol 2021 41:1942-1955 PMC8269748
4. Siebert AE, Maroney SA, Martinez ND, Mast AE: Intrauterine lethality in Tfpi gene disrupted mice is differentially suppressed during mid- and late-gestation by platelet TFPIα overexpression. J Thromb Haemost 2021 19:1483-1492. PMC8165032
5. Maroney SA, Westrick RJ, Cleuren AC, Martinez ND, Siebert AE, Zogg M, Ginsburg D, Weiler H, Mast AE: Tissue factor pathway inhibitor is required for cerebrovascular development in mice. Blood 2021 137:258-268. PMC7820871
6. Peterson JA, Maroney SA, Martinez ND, Mast AE: A major reservoir for heparin-releasable TFPIα is extracellular matrix. Arter Thromb and Vasc Biol 2021 41:1942-1955 PMC8269748
7. Baumann Kreuziger L, Edgren G, Hauser RG, Zaccaro D, Kiss J, Westlake M, Brambilia D, Mast AE: Red blood cell transfusion does not increase risk of venous or arterial thrombosis during hospitalization. Am. J. Hematol 2021 96:218-225. PMC8142264
8. Liu H, Burns RT, Spencer BR, Page GP, Mast AE: Demographic, clinical, and biochemical predictors of pica in a large cohort of blood donors. Transfusion 2021 61:2090-2098 PMC8571648
9. Mast AE, Szabo A, Stone M, Cable RG, Spencer BR, Kiss JE: The benefits of iron supplementation following blood donation vary with baseline iron status. Am. J. Hematol 2020 95:784-791. PMC7393577
10. Mast AE, Langer JC, Guo Y, Bialkowski W, Spencer BR, Lee T-H, Kiss J, Cable RG, Brambilla D, Busch MP, Page GP: Genetic and behavioral modification of hemoglobin and iron status among first-time and high-intensity blood donors. Transfusion 2020 60:747-758. PMC7393610
11. Spencer BR, Guo Y, Cable RG, Kiss JK, Busch MP, Page GP, Endres-Dighe SM, Kleinman S, Glynn SA, Mast AE: Iron status and risk factors for iron depletion in a racially/ethnically diverse blood donor population. Transfusion 2019, 59:3146-3156. PMC7028389
12. Spencer BR, Bialkowski W, Creel DV, Cable RG, Kiss JE, Stone M, McClure C, Kleinman S, Glynn SA, Mast AE: Elevated Risk for Iron Depletion in High-School Age Blood Donors. Transfusion 2019, 59:1706-1716. PMC6499707