Page ContentOverviewThe major goal in our laboratory is to understand how the lymphatic vasculature regulates inflammation and wound healing. Lymphatic vessels provide fluid egress and cell transport in peripheral tissues; important properties that contribute to the inflammatory and wound recovery responses. We use contemporary molecular biology and genetic strategies to investigate the cellular and molecular mechanisms that regulate lymphatic vessel remodeling. Project 1 Integrin regulated lymphatic vessel growth and regression.These studies are designed to understand how α and β integrins regulate lymphatic vessel growth or regression. We use several approaches including in vitro studies and an in vivo corneal experimental model to address these questions. Project 2 The role of the lymphatic vasculature during wound recovery.The goal of this project is the development of a genetically modified mouse strain using CRE/LOX technology that will enable us to temporally induce deletion of β1 integrin in lymphatic endothelium in the adult mouse. We will coordinate β1 integrin deletion with lymphatic vessel growth or regression to determine the effects of β1 integrin deletion on these processes and corneal health.Conditional genetic approaches to modify genes of interest in the lymphatic vasculature are central features of both projects. We use coordinated intravital and conventional immunofluorescent microscopy techniques to visualize lymphatic vessel remodeling in the cornea and skin. Biochemical and histological studies help us interpret how induced perturbations of the lymphatic vasculature affect inflammatory and wound recovery responses. MHC II positive cells (green) in corneal lymphatic vessel (red).FundingIntegrin regulation of corneal lymphatic vessel growth Identification: 1R01EY021571-01 Sponsor: National Eye Institute, National Institutes of HealthRole: PI Staff Richard M. Tempero, M.D. Ph.D.Alicia L. Connor, B.S.Darci M. Fink, B.S.PublicationsLymphatic Vessel Memory Stimulated by Recurrent Inflammation. Kelley PM, Connor AL, Tempero RM.Am J Pathol. 2013 Apr 8. doi:pii: S0002-9440(13)00203-4. 10.1016/j.ajpath.2013.02.025. [Epub ahead of print]Glucocorticoids suppress corneal lymphangiogenesis.Steele MM, Kelley PM, Schieler AM, Tempero RM.Cornea. 2011 Dec;30(12):1442-7. doi: 10.1097/ICO.0b013e318213f39fRegressed lymphatic vessels develop during corneal repair. Kelley PM, Steele MM, Tempero RM.Lab Invest. 2011 Nov;91(11):1643-51. doi: 10.1038/labinvest.2011.121. Epub 2011 Aug 22.β1 integrin regulates MMP-10 dependant tubulogenesis in human lymphatic endothelial cells. Steele MM, Schieler AM, Kelley PM, Tempero RM.Matrix Biol. 2011 Apr;30(3):218-24. doi: 10.1016/j.matbio.2011.03.001. Epub 2011 Mar 23.Lymphatic vessel hypertrophy in inflamed human tonsils. Kelley PM, Tempero RM. Lymphat Res Biol. 2010 Jun;8(2):121-6. doi: 10.1089/lrb.2009.0026.Lymphatic malformations: review of current treatment. Perkins JA, Manning SC, Tempero RM, Cunningham MJ, Edmonds JL Jr, Hoffer FA, Egbert MA. Otolaryngol Head Neck Surg. 2010 Jun;142(6):795-803, 803.e1. doi: 10.1016/j.otohns.2010.02.026.Lymphatic malformations: current cellular and clinical investigations. Perkins JA, Manning SC, Tempero RM, Cunningham MJ, Edmonds JL Jr, Hoffer FA, Egbert MA. Otolaryngol Head Neck Surg. 2010 Jun;142(6):789-94. doi: 10.1016/j.otohns.2010.02.025.Integrin alpha1beta1 regulates matrix metalloproteinases via P38 mitogen-activated protein kinase in mesangial cells: implications for Alport syndrome. Cosgrove D, Meehan DT, Delimont D, Pozzi A, Chen X, Rodgers KD, Tempero RM, Zallocchi M, Rao VH.Am J Pathol. 2008 Mar;172(3):761-73. doi: 10.2353/ajpath.2008.070473. Epub 2008 Feb 7.