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
2014 - Outstanding Advisor of the Year Award, UIUC Medical Scholars Program
2013 - The Sol Sherry Distinguished Lecture in Thrombosis, given at American Heart Association Scientific Sessions, Dallas, TX
2011 - Biennial Investigator Recognition Award for Contributions to Haemostasis; awarded in Kyoto, Japan, at the XXIIIrd Congress of the International Society on Thrombosis & Haemostasis
2007 - Alumni Discretionary Award, College of Liberal Arts & Sciences, UIUC
2006 - The Theodore Spaet Memorial Lecture, Montefiore Medical Center, Albert Einstein College of Medicine
1991 - The Owren Lecture, University of Oslo, Norway
Polyphosphate, Zn2+ and high-molecular-weight kininogen modulate individual reactions of the contact pathway of blood clotting.
Wang Y, Ivanov I, Smith SA, Gailani D, Morrissey JH.
J Thromb Haemost. 2019; in press.
Inorganic polyphosphate interacts with nucleolar and glycosomal proteins in trypanosomatids.
Negreiros RS, Lander N, Huang G, Cordeiro CD, Smith SA, Morrissey JH, Docampo R.
Mol Microbiol. 2018; 110: 973-94.
DNA ladders can be used to size polyphosphate resolved by polyacrylamide gel electrophoresis.
Smith SA, Wang Y, Morrissey JH.
Electrophoresis. 2018; 39: 2454-59.
Ability of Polyphosphate and Nucleic Acids to Trigger Blood Clotting: Some Observations and Caveats.
Smith SA, Gajsiewicz JM, Morrissey JH.
Front Med. 2018; 5: 107.
Enzymatically oxidized phospholipids restore thrombin generation in coagulation factor deficiencies.
Slatter DA, Percy CL, Allen-Redpath K, Gajsiewicz JM, Brooks NJ, Clayton A, Tyrrell VJ, Rosas M, Lauder SN, Watson A, Dul M, Garcia-Diaz Y, Aldrovandi M, Heurich M, Hall J, Morrissey JH, Lacroix-Desmazes S, Delignat S, Jenkins PV, Collins PW, O'Donnell VB.
JCI Insight. 2018; 3: e98459.
Design of Polyphosphate Inhibitors: A Molecular Dynamics Investigation on Polyethylene Glycol-Linked Cationic Binding Groups.
Mafi A, Abbina S, Kalathottukaren MT, Morrissey JH, Haynes C, Kizhakkedathu JN, Pfaendtner J, Chou KC.
Biomacromolecules. 2018; 19: 1358-67.
Multiplexed silicon photonic sensor arrays enable facile characterization of coagulation protein binding to nanodiscs with variable lipid content.
Muehl EM, Gajsiewicz JM, Medfisch SM, Wiersma ZSB, Morrissey JH, Bailey RC.
J Biol Chem. 2017; 292: 16249-56.
Lipid specificity of the membrane binding domain of coagulation factor X.
Muller MP, Wang Y, Morrissey JH, Tajkhorshid E.
J Thromb Haemost. 2017; 15: 2005-16.
Silica particles contribute to the procoagulant activity of DNA and polyphosphate isolated using commercial kits.
Smith SA, Baker CJ, Gajsiewicz JM, Morrissey JH.
Blood. 2017; 130: 88-91.
Polyphosphate and RNA Differentially Modulate the Contact Pathway of Blood Clotting.
Gajsiewicz JM, Smith SA, Morrissey JH.
J Biol Chem. 2017; 292: 1808-14.
For a list of publications from Pubmed, click HERE