Alan E. Mast, M.D., Ph.D.
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| Alan E. Mast, M.D., Ph.D. |
Investigator
Blood Research Institute
BloodCenter of Wisconsin
Associate Medical Director, Medical Services
BloodCenter of Wisconsin
Associate Professor, Department of Pathology
Associate Professor, Department of Cell Biology, Neurobiology
and Anatomy
Medical College of Wisconsin
M.D., Ph.D., Duke University, 1991
Selected Publications
Grant Support
Invited Lectures
Laboratory Staff
Contact Information
Research Interests
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
1) 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 TFPI. TFPI inhibits proteases in the very early stages of blood coagulation. 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. 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 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 vivo. The results of these studies will shed new light on a wide range of human diseases that are associated or caused by intravascular blood clots. We have recently demonstrated in mouse models that TFPI produced by the endothelial cells lining blood vessels as well as by platelets is important for preventing blood clots from forming in the brain. We are optimistic that our continued investigation of the physiological mechanisms underlying how TFPI functions in brain tissue will lead to new understanding of the causes and risk factors for stroke as well as other brain diseases that are associated with excess blood clotting such as Alzheimer’s disease.
2) Clinical and Translational Studies:
a. Blood donation removes a large amount of iron from the blood donor. This results in a large number of donors becoming iron deficient and developing iron deficiency anemia. However, some donors can donate blood repeatedly over many years and not develop iron deficiency anemia. We have performed studies of these donors to define their behavioral, biochemical and genetic characteristics that allow them to donate so frequently.
b. Our laboratory is leading a large epidemiological study performed in collaboration with other scientists in the National Heart Lung and Blood Institute’s Retroviral Epidemiology Donor Study II (REDSII) group. This study investigates low hematocrit deferral in over 700,000 blood donors from across the country in order to define demographic features of blood donors that increase or decrease their risk for having low hematocrit deferral. These studies are important because approximately 10% of people attempting to donate blood can not donate because they have low hematocrit. Identification of new strategies to decrease these deferrals could have a significant impact on the national blood supply.
c. As mentioned above, many people who attempt to donate blood are found to have anemia. There are many causes for anemia including nutritional deficiency, repeated blood donation, arthritis and diabetes. However, of particular concern in blood donors who represent a generally healthy segment of the population are “invisible” causes of anemia such as pre-malignant or malignant lesions within the gastrointestinal tract. In collaboration with scientists at the Medical College of Wisconsin and the National Anemia Action Council we have developed a new informational pamphlet based on the recommendations from two focus groups consisting of a total of 25 donors that had been deferred for low hematocrit. We are currently testing the ability of this pamphlet to influence the correct donors (i.e. those with high risk for a medically treatable cause for anemia) to seek medical care in a randomized study. We feel that the development of effective educational programs for blood donors with anemia represents a highly efficient and heretofore overlooked use of blood/plasma centers to significantly improve public health in the United States.
Selected Publications
Selected Basic Science Publications:
· Lockett JM, Mast AE: The contribution of the region between Gly-160 and the end of the third Kunitz domain to the anticoagulant activity of tissue factor pathway inhibitor. Biochemistry 2002, 41:4989-4997
· Cunningham AC, Hasty KA, Enghild JJ, Mast AE: Structural and functional characterization of tissue factor pathway inhibitor following degradation by matrix metalloproteinase-8. Biochem J 2002, 367:451-458
· Mast AE, Acharya N, Malecha MJ, Hall CL, Dietzen DJ: Characterization of the association of tissue factor pathway inhibitor with human placenta. Arter. Thromb. and Vasc. Biol. 2002, 2099-2104
· Maroney SA, Cunningham AC, Ferrel J, Hu R, Haberichter S, Mansbach CM, Brodsky RA, Dietzen DJ, Mast AE: A GPI-anchored co-receptor for tissue factor pathway inhibitor controls its intracellular trafficking and cell surface expression. J Thromb Hemost 2006, 4:1114-1124
· Donahue BS, Gailani D, Mast AE: Disposition of tissue factor pathway inhibitor during cardiopulmonary bypass. J Thromb Hemost 2006, 4:1011-1016
· Maroney SA, Haberichter SL, Friese P, Collins ML, Ferrel JP, Dale GL, Mast AE: Active tissue factor pathway inhibitor is expressed on the surface of coated platelets. Blood 2007, 109:1931-1937
· Timmer JC, Enoksson M, Wildfang E, Zhu W, Igarashi Y, Denault JB, Ma Y, Dummitt B, Chang YH, Mast AE, Eroshkin A, Smith J, Tao WA, Salvesen GS: Profiling constitutive proteolytic events in vivo. Biochem J 2007, 407:41-48
· Maroney SA, Cooley BC, Sood R, Weiler H, Mast AE: Combined tissue factor pathway inhibitor and thrombomodulin deficiency produces an augmented hypercoagulable state with tissue specific fibrin deposition. J Thromb Hemost, 2008, 6:111-117
· Maroney SA, Ferrel JP, Collins ML, Mast AE: TFPIg is an active alternatively spliced form of TFPI present in mice but not humans. J Thromb Hemost, 2008, 6:1344-1351
Selected Clinical and Translational Studies Publications:
· Mast AE, Blinder MA, Gronowski A, Chumley C, Scott MG: The clinical utility of the serum transferrin receptor level in the evaluation of iron deficiency anemia. Clin Chem 1998; 44:45-51
· Mast AE, Stadanlick JE, Lockett JM, Dietzen DJ: Solvent/detergent treated plasma has decreased antitrypsin activity and absent antiplasmin activity. Blood 1999; 94:3922-3927
· Mast AE, Blinder MA, Lu Q, Flax S, Dietzen DJ: The clinical utility of the reticulocyte hemoglobin content in the diagnosis of iron deficiency. Blood 2002, 99:1489-1491
· Mast AE, Blinder MA, Dietzen DJ: Test of the Month: Reticulocyte Hemoglobin Content. Am. J. Hematology 2008, 83:307-310
· Mast AE, Foster T, Pinder HL, Beczkiewicz CA, Bellissimo DB, Murphy AT, Kovacevic S, Wroblewski VJ, Withcher DR: Behavioral, biochemical and genetic analysis of iron metabolism in high intensity blood donors. Transfusion, 2008, 45:2197-2204
Grant Support
Basic Science Grant Support:
· Novo Nordisk Research Grant 9/2007-8/2009
· American Heart Association Established Investigator Award 1/2005-12/2009
· National Heart Lung and Blood Institute R01 Award 8/2002-12/2012
Clinical and Translational Studies Grant Support:
· National Heart Lung and Blood Institute Retroviral Epidemiology Donor Study (REDSII). 9/2004-8/2010
· Healthier Wisconsin Partnership Grant 7/08-6/09
Invited Lectures (Selected)
Basic Science Invited Lectures:
· “A GPI-anchored co-receptor for TFPI controls its intracellular trafficking and surface expression” Third Symposium on Hemostasis with Special Focus on Factor VIIa and Tissue Factor. University of North Carolina, Chapel Hill, NC (5/5/2006)
· “Cell Surface Associated TFPI” Gordon Conference on Hemostasis. Colby College, Waterville, ME (7/10/2006)
· “Overview of Hemostasis with a Focus on Cell Associated TFPI” Eastern Canadian Symposium on Hemostasis. Montreal Canada (9/14/2006)
· “Expression of TFPI and TFPIb in Endothelial Cells, Platelets and Tissues” Novo Nordisk, Copenhagen Denmark (3/5/2007)
· "Regulation of Intravascular Thrombus Formation by Endothelial and Platelet Associated TFPI" University of Chicago, Chicago IL (1/16/2008)
· “The Different Mouse TFPI Splice Variants” Novo Nordisk, Copenhagen Denmark (9/16/2008)
Clinical and Translational Studies Invited Lectures:
· “Behavioral and Biochemical Characteristics of “Superdonors” AABB Annual Meeting. Miami, FL (10/21/2006)
· “Blood Donation and Iron” Wisconsin Association of Blood Banks Annual Meeting, Appleton, WI (9/12/2008)
· “Iron Homeostasis in Frequent Blood Donors” AABB Annual Meeting, Montreal, Canada (10/4/2008)
Laboratory Staff
Employment Opportunities
If opportunities are available, they will be listed on the Employment page.
Contact Information
Phone: (414) 937-6310
Fax: (414) 937-6284
E-mail: alan.mast@bcw.edu
