Photo of Francis W. Luscinskas,  PhD

Francis W. Luscinskas, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-4337
Fax: (617) 525-4333


fluscinskas@rics.bwh.harvard.edu

Francis W. Luscinskas, PhD

Brigham And Women's Hospital

EDUCATIONAL TITLES

  • Professor, Pathology, Harvard Medical School
  • Associate Director, Vascular Research Division, Brigham And Women's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Luscinskas lab is interested in how circulating white blood cells, called leukocytes, are recruited to infected or injured organs and tissues. This process involves leukocyte migration across the vascular endothelial monolayer, which lines the entire vascular system. The emphasis is to understand the mechanisms underlying blood leukocyte adhesion and transmigration across the blood vessel wall during infection, injury or immune-specific responses. Since many patients receiving treatments for cancer have temporary loss of immune cell function and platelets and are at risk for infections or bleeding, it is important to understand how to facilitate improved immune cell surveillance in cancer patients.

Our laboratory developed an in vitro model to mimic small vessel blood flow characteristics, and combined it with live cell microscopy to observe leukocyte-endothelial cell adhesive interactions. We use viral vectors and CRISPR-Cas-9 technologies to add genes, delete (erase) genes, or to erase and replace genes that contain fluorescent tags in endothelial cells to study their dynamic behavior during leukocyte adhesion and transmigration with our microscopy system described above.

Ongoing projects include (1) the study of molecules that regulate leukocyte adhesion to endothelial cells or other surfaces. We focus on the molecule called CD47, also known as integrin associated protein. CD47 is necessary for integrins to adhere to surfaces. (2) CD47 plays a similar role to control integrin adhesion in endothelial cells, and CD47 also serves to integrate signals that coordinate passage of leukocytes. These projects rely on biophysical, cell biological and molecular biological approaches. (3) CD47 also regulates leukocytes that provide adoptive immunity, called T lymphocytes. Inhibition of CD47 can protect mice from models of neuroinflammation, and our lab is examining how this works in other mouse models.

Publications

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  • Zahr A, Alcaide P, Yang J, Jones A, Gregory M, Dela Paz NG, Patel-Hett S, Nevers T, Koirala A, Luscinskas FW, Saint-Geniez M, Ksander B, D'Amore PA, Argüeso P. Endomucin prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions. Nat Commun 2016; 7:10363. PubMed
  • Luscinskas FW, Leick M, Newton G, Nusrat A. Introduction for the special issue on "Tissue Barriers in Inflammation". Tissue Barriers 2015; 3:e1015825. PubMed
  • Herter JM, Grabie N, Cullere X, Azcutia V, Rosetti F, Bennett P, Herter-Sprie GS, Elyaman W, Luscinskas FW, Lichtman AH, Mayadas TN. AKAP9 regulates activation-induced retention of T lymphocytes at sites of inflammation. Nat Commun 2015; 6:10182. PubMed
  • Wang G, van Driel BJ, Liao G, O'Keeffe MS, Halibozek PJ, Flipse J, Yigit B, Azcutia V, Luscinskas FW, Wang N, Terhorst C. Migration of Myeloid Cells during Inflammation Is Differentially Regulated by the Cell Surface Receptors Slamf1 and Slamf8. PLoS ONE 2015; 10:e0121968. PubMed
  • Massaad MJ, Oyoshi MK, Kane J, Koduru S, Alcaide P, Nakamura F, Ramesh N, Luscinskas FW, Hartwig J, Geha RS. Binding of WIP to actin is essential for T cell actin cytoskeleton integrity and tissue homing. Mol Cell Biol 2014. PubMed
  • Brown JD, Lin CY, Duan Q, Griffin G, Federation AJ, Paranal RM, Bair S, Newton G, Lichtman AH, Kung AL, Yang T, Wang H, Luscinskas FW, Croce KJ, Bradner JE, Plutzky J. NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis. Mol Cell 2014. PubMed
  • Leick M, Azcutia V, Newton G, Luscinskas FW. Leukocyte recruitment in inflammation: basic concepts and new mechanistic insights based on new models and microscopic imaging technologies. Cell Tissue Res 2014; 355:647-56. PubMed
  • Luscinskas FW. Neutrophil recruitment: perivascular macrophages 'duke it out' with Staphylococcus aureus. Nat Immunol 2013; 15:10-1. PubMed
  • Martinelli R, Newton G, Carman CV, Greenwood J, Luscinskas FW. Novel role of CD47 in rat microvascular endothelium: signaling and regulation of T-cell transendothelial migration. Arterioscler Thromb Vasc Biol 2013; 33:2566-76. PubMed
  • Azcutia V, Routledge M, Williams MR, Newton G, Frazier WA, Manica A, Croce KJ, Parkos CA, Schmider AB, Turman MV, Soberman RJ, Luscinskas FW. CD47 plays a critical role in T-cell recruitment by regulation of LFA-1 and VLA-4 integrin adhesive functions. Mol Biol Cell 2013; 24:3358-68. PubMed
  • Azcutia V, Stefanidakis M, Tsuboi N, Mayadas T, Croce KJ, Fukuda D, Aikawa M, Newton G, Luscinskas FW. Endothelial CD47 promotes vascular endothelial-cadherin tyrosine phosphorylation and participates in T cell recruitment at sites of inflammation in vivo. J Immunol 2012; 189:2553-62. PubMed
  • Alcaide P, Martinelli R, Newton G, Williams MR, Adam A, Vincent PA, Luscinskas FW. p120-Catenin prevents neutrophil transmigration independently of RhoA inhibition by impairing Src dependent VE-cadherin phosphorylation. Am J Physiol Cell Physiol 2012; 303:C385-95. PubMed
  • Griffin GK, Newton G, Tarrio ML, Bu DX, Maganto-Garcia E, Azcutia V, Alcaide P, Grabie N, Luscinskas FW, Croce KJ, Lichtman AH. IL-17 and TNF-α sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation. J Immunol 2012; 188:6287-99. PubMed
  • Zhang J, Alcaide P, Liu L, Sun J, He A, Luscinskas FW, Shi GP. Regulation of endothelial cell adhesion molecule expression by mast cells, macrophages, and neutrophils. PLoS ONE 2011; 6:e14525. PubMed
  • Koduru S, Kumar L, Massaad MJ, Ramesh N, Le Bras S, Ozcan E, Oyoshi MK, Kaku M, Fujiwara Y, Kremer L, King S, Fuhlbrigge R, Rodig S, Sage P, Carman C, Alcaide P, Luscinskas FW, Geha RS. Cdc42 interacting protein 4 (CIP4) is essential for integrin-dependent T-cell trafficking. Proc Natl Acad Sci U S A 2010; 107:16252-6. PubMed
  • Alcaide P,Auerbach S,Luscinskas FW. Neutrophil recruitment under shear flow: it's all about endothelial cell rings and gaps. Microcirculation 2008; 16:43-57. PubMed
  • Alcaide P,Newton G,Auerbach S,Sehrawat S,Mayadas TN,Golan DE,Yacono P,Vincent P,Kowalczyk A,Luscinskas FW. p120-Catenin regulates leukocyte transmigration through an effect on VE-cadherin phosphorylation. Blood 2008; 112:2770-9. PubMed
  • Stefanidakis M,Newton G,Lee WY,Parkos CA,Luscinskas FW. Endothelial CD47 interaction with SIRPgamma is required for human T-cell transendothelial migration under shear flow conditions in vitro. Blood 2008; 112:1280-9. PubMed
  • Rabodzey A, Alcaide P, Luscinskas FW, Ladoux B. Mechanical forces induced by the transendothelial migration of human neutrophils. Biophys J 2008; 95:1428-38. PubMed
  • Alcaide P, King SL, Dimitroff CJ, Lim YC, Fuhlbrigge RC, Luscinskas FW. The 130-kDa glycoform of CD43 functions as an E-selectin ligand for activated Th1 cells in vitro and in delayed-type hypersensitivity reactions in vivo. J Invest Dermatol 2007; 127:1964-72. PubMed
  • Alcaide P, Jones TG, Lord GM, Glimcher LH, Hallgren J, Arinobu Y, Akashi K, Paterson AM, Gurish MA, Luscinskas FW. Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue. J Exp Med 2007; 204:431-9. PubMed
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