James "Jim" H. Morrissey

jhmorris@illinois.edu

323 Roger Adams Lab (office)
Office: (217) 265-4036
Lab: (217) 265-5424
Fax: (217) 265-5290

Mail to: Dept. of Biochemistry
University of Illinois
323 Roger Adams Lab, MC-712
600 S. Mathews Ave.
Urbana, IL 61801
Lab Page
Curriculum Vita
Video Interview

James "Jim" H. Morrissey

Professor and Acting Head of Biochemistry
Roy and Eva Hong Professor of Molecular and Cellular Biology

Research Topics

Enzymology, Membrane Biology, Protein Structure

Education

B.S. M.S. 1975 University of California, Irvine
Ph.D. 1980 University of California, San Diego
Postdoc. 1981-1983 Oxford University, 1983-1984 The Scripps Research Institute

Teaching Interests

Protein-phospholipid interactions; regulation of protease cascades; blood clotting; polyphosphate

A number of important biological processes, including apoptosis, the complement system and blood coagulation, are controlled by protease cascades. A key regulatory feature of such cascades is the modulation of protease function by highly specific protein cofactors, and interestingly, these cascades often can only take place on membrane surfaces. Although much is known about the general catalytic mechanism of serine proteases, far less is known about the roles of protein cofactors and membrane surfaces in regulating protease function. In our lab we are studying serine proteases in the blood clotting cascade with a goal of understanding the contributions of protein-protein and protein-phospholipid interactions to catalysis.  Very recently, we have discovered that polyphosphate (a polymer of inorganic phosphate) potently modulates blood clotting and inflammation. How it does this is not well understood.

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?
  • What are the mechanisms by which polyphosphate modulates blood clotting and inflammation?
  • As a spinoff from these basic studies, we are working to develop:
    • Improved hemostatic agents to treat surgical and traumatic bleeding
    • Novel antithrombotic/anti-inflammatory agents
    • Improved diagnostic tests for identifying persons at risk of thrombotic disease

Awards

1991: The Owren Lecture, University of Oslo, Norway
2006: The Theodore Spaet Memorial Lecture, Montefiore Medical Center, Albert Einstein College of Medicine
2007: Alumni Discretionary Award, College of Liberal Arts & Sciences, UIUC
2011: Biennial Investigator Recognition Award for Contributions to Haemostasis; awarded in Kyoto, Japan, at the XXIIIrd Congress of the International Society on Thrombosis & Haemostasis
2013: Sol Sherry Distinguished Lecture in Thrombosis, given at American Heart Association Scientific Sessions, Dallas, TX

Representative Publications

Hebbard CFF, Wang Y, Baker CJ, and Morrissey JH. Synthesis and evaluation of chromogenic and fluorogenic substrates for high-throughput detection of enzymes that hydrolyze inorganic polyphosphate. Biomacromolecules, In Press. -- PubMed link

Wat JM, Foley JH, Krisinger MJ, Ocariza LM, Lei V, Wasney GA, Lameignere E, Strynadka NC, Smith SA, Morrissey JH, and Conway EM. Polyphosphate suppresses complement via the terminal pathway. Blood 123:768-776, 2014. Rated "Recommended" by the Faculty of 1000 -- PubMed link

Ke K, Yuan J, and Morrissey JH. Tissue factor residues that putatively interact with membrane phospholipids. PLoS ONE 9:e88675, 2014. -- PubMed link

Tavoosi N, Smith SA, Davis-Harrison RL, and Morrissey JH. Factor VII and protein C are phosphatidic acid-binding proteins. Biochemistry 52:5545-5552, 2013. -- PubMed link

Smith SA, Choi SH, Collins JNR, Travers RJ, Cooley BC, and Morrissey JH. Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation. Blood 120:5103-5110, 2012. [Designated the "Plenary Paper" for the December 20, 2012 issue of this journal.] -- Press Release -- PubMed link

Morrissey JH, Choi SH, and Smith S.A. Polyphosphate: an ancient molecule that links platelets, coagulation and inflammation. Blood 119:5972-5979, 2012. -- PubMed link

Choi SH, Smith SA, and Morrissey JH. Polyphosphate is a cofactor for the activation of factor XI by thrombin. Blood 118:6963-6970, 2011. Commentary -- PubMed link

Tavoosi N, Davis-Harrison RL, Pogorelov TV, Ohkubo YZ, Arcario MJ, Clay MC, Rienstra CM, Tajkhorshid E, Morrissey JH. Molecular determinants of phospholipid synergy in blood clotting. J Biol Chem 285:23247-23253, 2011. Highlighted on the cover of the JBC -- Press Release -- PubMed link

Boettcher JM, Davis-Harrison RL, Clay MC, Nieuwkoop AJ, Ohkubo YZ, Tajkhorshid E, Morrissey JH, Rienstra CM. Atomic view of calcium-induced clustering of phosphatidylserine in mixed lipid bilayers. Biochemistry 50:2264-2273, 2011. PubMed link

Semeraro F, Ammollo CT, Morrissey JH, Dale GL, Friese P, Esmon NL, and Esmon, CT. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: Involvement of platelet TLR2 and TLR4. Blood 118:1952-1961, 2011. Commentary -- PubMed link

Choi SH, Collins JN, Smith SA, Davis-Harrison RL, Rienstra CM, Morrissey JH. Phosphoramidate end labeling of inorganic polyphosphates: facile manipulation of polyphosphate for investigating and modulating its biological activities. Biochemistry 49:9935-9941, 2010. Rated "Recommended" by the Faculty of 1000 -- PubMed link

Smith SA, Choi SH, Davis-Harrison R, Huyck J, Boettcher J, Reinstra CM, Morrissey JH. Polyphosphate exerts differential effects on blood clotting, depending on polymer size. Blood 116:4353-4359, 2010. Commentary -- PubMed link

Ohkubo YZ, Morrissey JH, and Tajkhorshid E. Dynamical view of membrane binding and complex formation of human factor VIIa and tissue factor. J Thromb Haemost 8:1044-1053, 2010. PubMed link

Müller F, Mutch NJ, Schenk WA, Smith SA, Esterl L, Spronk HM, Schmidbauer S, Gahl WA, Morrissey JH, and Renné T. Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 139:1143-1156, 2009. Rated "Exceptional" by the Faculty of 1000 -- PubMed link

Smith, S. A. and J. H. Morrissey. Polyphosphate enhances fibrin clot structure. Blood 112:2810-2816, 2008. Commentary -- Rated "Must Read" by the Faculty of 1000 -- PubMed link

Shaw, A. W., V. S. Pureza, S. G. Sligar, and J. H. Morrissey. The local phospholipid environment modulates the activation of blood clotting. J Biol Chem 282:6556-6563, 2007. PubMed link

Smith, S. A., N. J. Mutch, D. Baskar, P. Rohloff, R. Docampo, and J. H. Morrissey. Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci USA 103:903-908, 2006. Rated "Recommended" by the Faculty of 1000 -- PubMed link

Complete Publications List