Abstract

? The overall long-term goal of this multidisciplinary research program is to apply new optical technology to investigate early changes associated with cellular immune response and to monitor response to therapy over time in vivo and at the cellular level. Specifically, we proposed to develop in vivo immunofluorescence microscopy for imaging specific cell surface markers expressed by vascular and lymphatic endothelial cells, circulating leukocytes, and tissue dendritic cells. The technology that enables noninvasive, real-time cellular imaging is a video rate confocal and multiphoton fluorescence microscope that we recently developed in our laboratory. We will apply this technology to study important steps involved in the regulation of cellular immune response in vivo, including endothelial cell activation, leukocyteendothelial interaction, and dendritic cell recruitment and migration. In addition, we proposed to develop an in vivo flow cytometer, a novel technology for real-time, noninvasive detection and quantification of circulating cells that are tagged with fluorescent antibodies or antibody fragments. We will use this system to monitor changes in specific T cell population in response to immunomodulation, to detect circulating tumor cells and to investigate the correlation between tumor cell shedding and metastatic potential. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB000664-03
Application #
6792092
Study Section
Special Emphasis Panel (ZRG1-SSS-X (30))
Program Officer
Zhang, Yantian
Project Start
2002-09-15
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
3
Fiscal Year
2004
Total Cost
$416,334
Indirect Cost

  Institution

Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199

  Publications

Imitola, Jaime; Cote, Daniel; Rasmussen, Stine et al. (2011) Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice. J Biomed Opt 16:021109
Pitsillides, Costas M; Runnels, Judith M; Spencer, Joel A et al. (2011) Cell labeling approaches for fluorescence-based in vivo flow cytometry. Cytometry A 79:758-65
Horner, Benjamin M; Ferguson, Kelly K; Randolph, Mark A et al. (2010) In vivo observations of cell trafficking in allotransplanted vascularized skin flaps and conventional skin grafts. J Plast Reconstr Aesthet Surg 63:711-9
Azab, Abdel Kareem; Runnels, Judith M; Pitsillides, Costas et al. (2009) CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood 113:4341-51
Azab, Abdel Kareem; Azab, Feda; Blotta, Simona et al. (2009) RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma. Blood 114:619-29
Biss, David P; Sumorok, Daniel; Burns, Stephen A et al. (2007) In vivo fluorescent imaging of the mouse retina using adaptive optics. Opt Lett 32:659-61
Bogdanov Jr, Alexei A; Lin, Charles P; Kang, Hye-Won (2007) Optical imaging of the adoptive transfer of human endothelial cells in mice using anti-human CD31 monoclonal antibody. Pharm Res 24:1186-92
Boutrus, Steven; Greiner, Cherry; Hwu, Derrick et al. (2007) Portable two-color in vivo flow cytometer for real-time detection of fluorescently-labeled circulating cells. J Biomed Opt 12:020507
Alsayed, Yazan; Ngo, Hai; Runnels, Judith et al. (2007) Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma. Blood 109:2708-17
Kosharskyy, Boleslav; Solban, Nicolas; Chang, Sung K et al. (2006) A mechanism-based combination therapy reduces local tumor growth and metastasis in an orthotopic model of prostate cancer. Cancer Res 66:10953-8

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