Room 4301B MSRB III, 1150 West Medical Center Drive
Ann Arbor, MI 48109
Available to mentor
My lab's research focuses on understanding how the human blood clotting system functions in health (normal hemostasis) and disease (thrombosis). In particular, we conduct biochemical studies aimed at elucidating the underlying mechanisms controlling the complex series of enzyme-activation events that make up the blood clotting cascade, which lead ultimately to the formation of a fibrin clot and activated platelets. Thrombosis is the formation of unwanted blood clots inside arteries and veins, which represents one of the leading causes of disability and death worldwide. For this reason, it is critically important to understand how the the blood coagulation is regulated. My lab's research program is a combination of basic and translational research.
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PhDUniversity of California, San Diego, La Jolla, 1980
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Center MemberSamuel and Jean Frankel Cardiovascular Center
We are currently focusing on the following research questions:
-- How do the serine proteases of the blood clotting system assemble together with specific regulatory proteins on membrane surfaces?
-- These enzyme activation events are thousands of times less active in solution than on membrane surfaces. Why are membranes required for efficient proteolysis by these enzymes? What role do specific phospholipid types play in modulating the activity of blood clotting proteases?
-- We recently discovered that inorganic polyphosphate (secreted from activated platelets and abundant in many microorganisms) is a novel and highly potent modulator of blood clotting and fibrinolysis. It is also proinflammatory. What are the mechanisms by which polyphosphate exerts these biologic activities?
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La CC, Smith SA, Kalathottukaren MT, Haynes CA, Morrissey JH, Kizhakkedathu JN. Adv Healthc Mater, 2024 Aug; 13 (20): e2400108Journal ArticleExternal Trigger Free Charge Switchable Cationic Ligands in the Design of Safe and Effective Universal Heparin Antidote.
DOI:10.1002/adhm.202400108 PMID: 38537246 -
Sedzro JC, Smith SA, Scott A, Wang Y, Travers RJ, Hemp R, Morse CN, Morrissey JH. Res Pract Thromb Haemost, 2024 Aug; 8 (6): 102550Journal ArticleAntipolyphosphate monoclonal antibodies derived from autoimmune mice.
DOI:10.1016/j.rpth.2024.102550 PMID: 39309228 -
Morrissey JH. Arterioscler Thromb Vasc Biol, 2024 Jul; 44 (7): 1671 - 1673.Journal ArticleHRG to the Rescue.
DOI:10.1161/ATVBAHA.124.321178 PMID: 38924441 -
MacArthur TA, Goswami J, Navarro SM, Vappala S, La CC, Yudin N, Zietlow J, Smith SA, Morrissey JH, Spears GM, Bailey KR, Dong J-F, Kozar RA, Kizhakkedathu JN, Park MS. Shock, 2024 Jun 1; 61 (6): 848 - 854.Journal ArticleINHIBITORS OF INORGANIC POLYPHOSPHATE AND NUCLEIC ACIDS ATTENUATE IN VITRO THROMBIN GENERATION IN PLASMA FROM TRAUMA PATIENTS.
DOI:10.1097/SHK.0000000000002362 PMID: 38662595 -
Hajeyah AA, Protty MB, Paul D, Costa D, Omidvar N, Morgan B, Iwasaki Y, McGill B, Jenkins PV, Yousef Z, Allen-Redpath K, Soyama S, Choudhury A, Mitra R, Yaqoob P, Morrissey JH, Collins PW, O'Donnell VB. J Lipid Res, 2024 Jan; 65 (1): 100484Journal ArticlePhosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease.
DOI:10.1016/j.jlr.2023.100484 PMID: 38103786 -
Lillicrap D, Morrissey JH. J Thromb Haemost, 2023 Dec; 21 (12): 3285 - 3286.Journal ArticleLooking Back-And Forward.
DOI:10.1016/j.jtha.2023.09.024 PMID: 38000849 -
La CC, Smith SA, Vappala S, Adili R, Luke CE, Abbina S, Luo HD, Chafeeva I, Drayton M, Creagh LA, de Guadalupe Jaraquemada-Peláez M, Rhoads N, Kalathottukaren MT, Henke PK, Straus SK, Du C, Conway EM, Holinstat M, Haynes CA, Morrissey JH, Kizhakkedathu JN. Nat Commun, 2023 Apr 26; 14 (1): 2177Journal ArticleSmart thrombosis inhibitors without bleeding side effects via charge tunable ligand design.
DOI:10.1038/s41467-023-37709-0 PMID: 37100783 -
Cheng KJ, De Lio AM, Jain R, Paul D, Morrissey JH, Pogorelov TV. Biochemistry, 2023 Oct 17; 62 (20): 3020 - 3032.Journal ArticleLactadherin's Multistate Binding Predicts Stable Membrane-Bound Conformations of Factors V and VIII's C Domains.
DOI:10.1021/acs.biochem.3c00274 PMID: 37747791