Larry V. McIntire

Research Interests:

• Biomedical Engineering
• Rheology and Fluid Mechanics
• Tissue Engineering

Education:

• B.S. (1966) Cornell University
• Ph.D. (1970) Princeton University

Professor McIntire's research is focused on understanding the interplay between fluid mechanics, convective mass transport, cell biology, and molecular biology in the cardiovascular system. There are currently three main areas of special interest:

1. Flow modulation of adhesive interactions of blood borne cells and endothelial cells that line the walls of our arteries and veins. Applications include the immune response and cancer metastasis. To leave the bloodstream, circulating leukocytes must first attach to the vessel wall and then migrate through the endothelial cell monolayer. White cells utilize special types of membrane-associated molecules called adhesive receptors during transmigration, and both adhesion and migration occur in a dynamic environment. Combining video microscopy of model blood vessels with digital image processing, we are making substantial progress in understanding the molecular basis of these complex, highly regulated mechanisms. Similar processes occur in cancer metastasis, where malignantcells from a primary tumor enter the bloodstream and are transported to distant organs.
2. Development of models for thrombosis. We have utilized fluorescent video microscopy and digital image processing to visualize directly the process of mural thrombosis under conditions of controlled surface chemistry and blood flow rate. Convective transport model numerical simulations have been extremely useful in increasing our understanding of the local concentrations of platelet activating substances near growing thrombi.
3. The role of blood flow and resultant fluid mechanical forces in modulation of intracellular metabolism of vascular cells. We are using cultured endothelial cell monolayers in recirculating flow loops to study the effect of physiological flows on modulation of protein synthesis and secretion. Current work in this area includes developing more detailed knowledge of how a cell recognizes mechanical loadings and how this signal is transduced to the nucleus to initiate gene regulation. We have demonstrated selective flow regulation of secretion and messenger RNA levels in endothelial cells for several proteins and peptides. A knowledge of the control at the DNA level (gene regulation) is still missing, however. We hope to identify stress-sensitive gene promoter elements.

Selected Publications

1. Dong, J-F., Berndt, M.C., Schade, A., McIntire, L.V., Andrews, R.K., and López, J.A., "Ristocetin-Dependent, but not Botrocetin-Dependent, Binding of von Willebrand Factor to the Platelet Glycoprotein Ib-IX-V Complex Correlates with Shear-Dependent Interactions", Blood, 97, 162-168 (2001).
2. McCormick, S.M., Eskin, S.G., McIntire, L.V., Lu, C-M., Russell, C.G., and Chittur, K.K., "DNA Microarray Reveals Changes in Gene Expression of Shear Stressed Human Endothelial Cells", Proc. Natl. Acad. Sci., 98, 8955-8960 (2001).
3. Dong, J-F., Ye, P., Schade, A.J., Gao, S., Romo, G.M., Turner, N., McIntire, L.V., and López, J.A., "Tyrosine Sulfation of Glycoprotein Iba ", J. of Biol. Chem. 276, 16690-16694 (2001).
4. Seo, S.M., McIntire, L.V., and Smith, C.W., "The Effects of IL-8, Gro-a and LTB4 on the Adhesive Kinetics LFA-1 and Mac-1 on Human Neutrophils", Amer. J. Physiol ., 281, C1568-C1578 (2001).
5. Nguyen, K.T., Frye, S.R., Eskin, S.G., Patterson, C., Runge, M.S., and McIntire, L.V., "Cyclic Strain Increases Protease-Activated Receptor-1 Expression in Vascular Smooth Muscle Cells", Hypertension 38, 1038-1043 (2001).
6. Turner, N., Moake, J.L., and McIntire, L.V., "Blockade of Both ADP Receptors, P2Y12 and P2Y1, is Required to Inhibit Platelet Aggregation in Whole Blood Under Flow", Blood 98, 3340-3345, (2001).
7. Arya, M., López, J.A., Romo, G.M., Dong, J-F., McIntire, L.V., Moake, J.L., and Anvari, B., "Measurement of the Binding Forces Between von Willebrand factor and Variants of Platelet Glycoprotein Ib-alpha Using Optical Tweezers" , Lasers in Surgery and Medicine 30, 306-312 (2002).
8. Brey, E., King, T.W., Johnson, C., McIntire, L.V., Reece, G.P., and Patrick, C.W., "A technique for quantitative 3D analysis of Microvascular Structure" Microvascular Research 63, 279-294 (2002).
9. Arya, M., Anvari, B., Romo, G.M., Cruz, M.A., Dong, J-F., McIntire, L.V., Moake, J.L., and López, J.A., "Ultralarge Multimers of von Willebrand Factor Form Spontaneous High-Strength Bonds with the Platelet Glycoprotein Ib_IX Complex: Studies Using Optical Tweezers", Blood 99, 3971-3977 (2002).
   
10. Shiu, Y-T, McIntire, L.V. and Udden, M.M., "Sickle Erythrocytes Increase Prostacyclin and Endothelin-1 Production by Cultured Human Endothelial Cells Under Flow Conditions" The European Journal of Hematology 68, 163-170 (2002).
    
    
    
    
    
    
    
    

CHEMICAL & BIOMOLECULAR ENGINEERING DEPT. MS-362
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