The theme of this program project is the inter-relation of mechanics, chemistry and hydrodynamics as underlying mechanisms in normal and pathological peripheral vascular function. Abnormalities in peripheral vascular function are integral to the pathology associated with the most serious diseases in Western society, including heart disease, stroke and cancer metastasis, and also play a fundamental role in less serious disorders involving inflammation and immune response. Four project are engaged in synergistic studies designed to reveal fundamental mechanisms underlying both normal and pathological phenomena in the peripheral vasculature. Dr. Hammer's project focuses on the chemical and hydrodynamic factors that govern interactions between neutrophils and endothelium, particularly on the role of cell-cell interactions and differences between in vitro studies, from which most of our current understanding comes, and clinically relevant events in vivo. The next project focuses on the important role that ion transport plays in neutrophils during cell activation in response to inflammatory agents and on the consequences of changes in ion transport on neutrophil adhesion and rheology, as well as on volume regulation in endothelial cells particularly under conditions of ischemia, and on the consequences of failed endothelial cell volume regulation in ischemia-reperfusion injury. The next project focused on the development of red cell membrane mechanical stability during erythropoiesis and the consequences of abnormal red cell deformability on cell function in the vasculature, as well as on the role of impingement and detachment forces in modulating neutrophil adhesive behavior. The final project focuses on the mechanisms underlying flow heterogeneities in the microvasculature, particularly on the consequences of abnormal red cell deformability on cell flux and microvascular flow, on the effects of changing vessel geometry on flow distribution and on mechanisms underlying heterogeneities in leukocyte distribution and behavior. The integration of these studies will result in improve understanding of basic mechanisms related to normal and pathological process within the peripheral vasculature, and could lead to the development of new strategies to relieve pathological conditions related to clinical disorder resulting from abnormalities in these processes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL018208-26
Application #
6182854
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
1988-07-01
Project End
2003-06-30
Budget Start
2000-07-11
Budget End
2001-06-30
Support Year
26
Fiscal Year
2000
Total Cost
$1,501,481
Indirect Cost
Name
University of Rochester
Department
Pharmacology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Vats, Kanika; Marsh, Graham; Harding, Kristen et al. (2017) Nanoscale physicochemical properties of chain- and step-growth polymerized PEG hydrogels affect cell-material interactions. J Biomed Mater Res A 105:1112-1122
Henry, Steven J; Crocker, John C; Hammer, Daniel A (2016) Motile Human Neutrophils Sense Ligand Density Over Their Entire Contact Area. Ann Biomed Eng 44:886-94
Marsh, Graham; Waugh, Richard E (2016) A simple approach for bioactive surface calibration using evanescent waves. J Microsc 262:245-51
Rocheleau, Anne D; Wang, Weiwei; King, Michael R (2016) Effect of Pseudopod Extensions on Neutrophil Hemodynamic Transport Near a Wall. Cell Mol Bioeng 9:85-95
Svetina, Saša; Kokot, Gašper; Kebe, Tjaša Švelc et al. (2016) A novel strain energy relationship for red blood cell membrane skeleton based on spectrin stiffness and its application to micropipette deformation. Biomech Model Mechanobiol 15:745-58
Rocheleau, Anne D; Cao, Thong M; Takitani, Tait et al. (2016) Comparison of human and mouse E-selectin binding to Sialyl-Lewis(x). BMC Struct Biol 16:10
MacKay, Joanna L; Hammer, Daniel A (2016) Stiff substrates enhance monocytic cell capture through E-selectin but not P-selectin. Integr Biol (Camb) 8:62-72
Hind, Laurel E; Lurier, Emily B; Dembo, Micah et al. (2016) Effect of M1-M2 Polarization on the Motility and Traction Stresses of Primary Human Macrophages. Cell Mol Bioeng 9:455-465
Lim, Kihong; Hyun, Young-Min; Lambert-Emo, Kris et al. (2015) Visualization of integrin Mac-1 in vivo. J Immunol Methods 426:120-7
Beste, Michael T; Lomakina, Elena B; Hammer, Daniel A et al. (2015) Immobilized IL-8 Triggers Phagocytosis and Dynamic Changes in Membrane Microtopology in Human Neutrophils. Ann Biomed Eng 43:2207-19

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