Areas of Interest
The research conducted in my laboratory focuses on understanding how cells regulate blood clotting in health and disease. The blood clotting system is activated when an enzyme (a specific plasma serine protease known as factor VIIa) binds to a particular integral membrane protein (known as tissue factor, or TF) on cell surfaces. The TF-VIIa-membrane complex triggers the blood clotting cascade by activating two plasma serine protease zymogens (factor IX and factor X) via limited proteolysis.
Thrombosis is the formation of unwanted blood clots inside arteries and veins, which represents the leading cause of disability and death in the world. Tissue factor is the protein that triggers thrombosis in many—possibly most—disease settings. For this reason, it is critically important to understand how the initiation of coagulation is controlled via tissue factor and factor VIIa.
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 cell surfaces and other 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 is a potent modulator of blood clotting and fibrinolysis. What’s the mechanism by which polyphosphate does this?
- As a spinoff from this basic research, we are also working to develop:
- Improved diagnostic tests for identifying persons at risk of thrombotic disease.
- Improved hemostatic agents to treat bleeding, including traumatic and surgical bleeding.
Honors & Awards
Outstanding Advisor of the Year Award, UIUC Medical Scholars Program, 2014
The Sol Sherry Distinguished Lecture in Thrombosis, given at American Heart Association Scientific Sessions, Dallas, TX, 2013
Biennial Investigator Recognition Award for Contributions to Haemostasis, awarded at the XXIIIrd Congress of the International Society on Thrombosis & Haemostasis, Kyoto, Japan, 2011
Alumni Discretionary Award, College of Liberal Arts & Sciences, UIUC, 2007
The Theodore Spaet Memorial Lecture, Montefiore Medical Center, Albert Einstein College of Medicine, 2006
The Owren Lecture, University of Oslo, Norway, 1991
Inhibitors of Polyphosphate and Neutrophil Extracellular Traps.
Vappala S, Smith SA, Kizhakkedathu JN, Morrissey JH.
Semin Thromb Hemost. 2023, in press.
Smart thrombosis inhibitors without bleeding side effects via charge tunable ligand design.
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; 14: 2177.
Genetic duplication of tissue factor reveals subfunctionalization in venous and arterial hemostasis.
Grzegorski SJ, Zhao Y, Richter CE, Ku CJ, Lavik KI, Paul D, Morrissey JH, Shavit JA.
PLoS Genet. 2022; 18: e1010534.
Understanding COVID-19-associated coagulopathy.
Conway EM, Mackman N, Warren RQ, Wolberg AS, Mosnier LO, Campbell RA, Gralinski LE, Rondina MT, van de Veerdonk FL, Hoffmeister KM, Griffin JH, Nugent D, Moon K, Morrissey JH.
Nat Rev Immunol. 2022; 22: 639–49.
Molecular View into Preferential Binding of the Factor VII Gla Domain to Phosphatidic Acid.
Muller MP, Morrissey JH, Tajkhorshid E.
Biochemistry. 2022; 61: 1694–703.
Influence of Steric Shield on Biocompatibility and Antithrombotic Activity of Dendritic Polyphosphate Inhibitor.
Abbina S, La CC, Vappala S, Kalathottukaren MT, Abbasi U, Gill A, Smith SA, Haynes CA, Morrissey JH, Kizhakkedathu JN.
Mol Pharm. 2022; 19: 1853–65.
Stoichiometric analysis reveals a unique phosphatidylserine binding site in coagulation factor X.
Paul D, Morrissey JH.
J Thromb Haemost. 2022; 20: 600–4.
For a list of publications from Pubmed, click HERE