About My Research
Additional Harvard Medical School Titles
- Professor of Pathology
- Co-Director, AMD Center of Excellence
- Member, PhD Program in Biological and Biomedical Sciences
Additional Mass. Eye and Ear Titles
- Director, Howe Laboratory
- Mass General Hospital Executive Committee on Research, Ophthalmology Representative
- Director of Research (Schepens Eye Research Institute of Massachusetts Eye and Ear)
- Ankeny Scholar in Molecular Biology of the Retina (Schepens Eye Research Institute of Massachusetts Eye and Ear)
- Senior Scientist
Center/Research Area Affiliations
Biography
At the forefront of angiogenesis research for more than three decades, Dr. D’Amore investigates the mechanisms of vascular growth and development. She is particularly interested in the role of polypeptide growth factors, such as VEGF and TGF-ß, and in investigating the contribution of cell-cell interactions in the cells of the vasculature.
Dr. D’Amore’s foremost transformative contributions include the identification of VEGF as the elusive “Factor X” that causes pathological blood vessel growth in blinding neovascular eye diseases. She also developed a widely used mouse model of oxygen-induced retinopathy that served as the cornerstone of many basic scientific and preclinical studies of vascular development and disease. Her laboratory’s description of the genomic organization and functional characterization of the mouse gene that encodes VEGF potentiated major advances in the understanding of the molecular and genetic mechanisms that underlie both developmental and pathological VEGF expression. Collectively, these studies helped form the scientific foundations of vascular-targeting therapies that are currently used to treat various cancers and intraocular vascular diseases, such as AMD and diabetic retinopathy. In recognition of this groundbreaking work, Dr. D’Amore was one of seven co-laureates of the 2014 Antonió Champalimaud Vision Award.
Dr. D’Amore’s studies have also uncovered important physiological roles of vascular growth factors—yielding crucial insight into the safe use of antiangiogenic therapies. Ongoing investigations are elucidating the molecular regulation of inflammation at the cellular level, the role of the endothelial glycocalyx in the regulation of angiogenesis, and the contribution of inflammation to the pathogenesis of AMD.
Education
1973: BA, Regis College, Weston
1977: PhD, Boston University
1987: MBA, Northeastern University
2011: Program on Negotiation, Harvard Law School
Postgraduate Training
1978-1979: Johns Hopkins Wilmer Eye Institute, Department of Ophthalmology,
1978-1981: Johns Hopkins University School of Medicine, Department of Physiological Chemistry
Honors
2018: Fellow of the American Academy of Arts & Sciences
2018: Barbara J. McNeil Faculty Award for Exceptional Institutional Service, Harvard Medical School and Harvard School of Dental Medicine
2018: Distinguished Alumni Award for Professional Achievement, Department of Biology, Boston University
2016: William Silen Lifetime Achievement in Mentoring Award, Harvard Medical School
2015: Proctor Medal, Association for Research and Vision Ophthalmology
2014: Laureate, António Champalimaud Vision Award
2014: Endre A. Balazs Prize, International Society for Eye Research
2013: American Medical Association Women Physicians Sector Mentorship Award
2013: Everett Mendelsohn Excellence in Mentoring Award, Harvard University
2012: 10th Annual Marc J. Mass Memorial Lecture, Dept. Molecular & Cellular Pathology, University of North Carolina, Chapel Hill, NC
2012: Rous-Whipple Award, American Society of Investigative Pathology
2011: Third Annual Judah Folkman, M.D. Lectureship, Longwood Area Vascular Biology Seminar Series, Harvard Medical School
2010: 5th Annual Jeffrey M. Isner, M.D. Endowed Memorial Lectureship
2009: Gold Fellow, Association for Research in Vision and Ophthalmology
2006: A. Clifford Barger Excellence in Mentoring Award, Harvard Medical School
2006: Senior Scientific Investigator Award, Research to Prevent Blindness
2006: Inaugural David Shepro Lecture, Boston University
2005: Excellence Award, The Schepens Eye Research Institute of Mass. Eye and Ear
2004: Elected Member of The Academy at Harvard Medical School
1998-2003: Jules and Doris Stein Research to Prevent Blindness Professorship
1994: Alcon Research Institute Award
1993: Cogan Award, Association for Research in Vision and Ophthalmology
1986-1991: American Heart Association Established Investigator Award
1979: Meyers Honor Award for Research in Ophthalmology
1977: Lamport Award, The Microcirculatory Society
- Introducing the Ocular Pathobiology Topic Category in The American Journal of Pathology. Am J Pathol. 2023 11; 193(11):1620-1621.
- Author Correction: Endomucin knockdown inhibits VEGF-induced endothelial cell migration, growth, and morphogenesis by modulating VEGFR2 signaling. Sci Rep. 2023 Oct 03; 13(1):16620.
- Cell culture models to study retinal pigment epithelium-related pathogenesis in age-related macular degeneration. Exp Eye Res. 2022 09; 222:109170.
- Macrophage efferocytosis with VEGFC and lymphangiogenesis: rescuing the broken heart. J Clin Invest. 2022 05 02; 132(9).
- Gerard (Jerry) Anthony Lutty, PhD- In Memoriam (1947-2021). Exp Eye Res. 2022 Jan 22; 216:108949.
- Discovery of sterically-hindered phenol compounds with potent cytoprotective activities against ox-LDL-induced retinal pigment epithelial cell death as a potential pharmacotherapy. Free Radic Biol Med. 2022 01; 178:360-368.
- Not Sure if You Are an Investigative Pathologist? Yes, You Are. Am J Pathol. 2022 01; 192(1):2-3.
- Galectin-3 Enhances Vascular Endothelial Growth Factor-A Receptor 2 Activity in the Presence of Vascular Endothelial Growth Factor. Front Cell Dev Biol. 2021; 9:734346.
- Update on the Role of the Endothelial Glycocalyx in Angiogenesis and Vascular Inflammation. Front Cell Dev Biol. 2021; 9:734276.
- Targeting of miR-33 ameliorates phenotypes linked to age-related macular degeneration. Mol Ther. 2021 07 07; 29(7):2281-2293.
- VEGFR1 signaling in retinal angiogenesis and microinflammation. Prog Retin Eye Res. 2021 09; 84:100954.
- Elements of the Endomucin Extracellular Domain Essential for VEGF-Induced VEGFR2 Activity. Cells. 2020 06 05; 9(6).
- ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface. J Biol Chem. 2020 05 08; 295(19):6641-6651.
- Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity. FASEB J. 2019 08; 33(8):9362-9373.
- Endomucin inhibits VEGF-induced endothelial cell migration, growth, and morphogenesis by modulating VEGFR2 signaling. Sci Rep. 2017 12 07; 7(1):17138.
- AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro. Invest Ophthalmol Vis Sci. 2017 12 01; 58(14):6082-6090.
- Introduction of the MDM2 T309G Mutation in Primary Human Retinal Epithelial Cells Enhances Experimental Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2017 10 01; 58(12):5361-5367.
- Genome editing abrogates angiogenesis in vivo. Nat Commun. 2017 07 24; 8(1):112.
- Therapeutic antibody targeting of Notch3 signaling prevents mural cell loss in CADASIL. J Exp Med. 2017 Aug 07; 214(8):2271-2282.
- Application of CRISPR-Cas9 in eye disease. Exp Eye Res. 2017 08; 161:116-123.
- Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis. Diabetes. 2017 07; 66(7):1950-1956.
- Editing VEGFR2 Blocks VEGF-Induced Activation of Akt and Tube Formation. Invest Ophthalmol Vis Sci. 2017 02 01; 58(2):1228-1236.
- Oxidized Lipoprotein Uptake Through the CD36 Receptor Activates the NLRP3 Inflammasome in Human Retinal Pigment Epithelial Cells. Invest Ophthalmol Vis Sci. 2016 09 01; 57(11):4704-12.
- Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease: An Analysis of Vascular Growth Factors with Clinical Correlation. Ophthalmology. 2016 09; 123(9):2028-36.
- Prevention of Proliferative Vitreoretinopathy by Suppression of Phosphatidylinositol 5-Phosphate 4-Kinases. Invest Ophthalmol Vis Sci. 2016 07 01; 57(8):3935-43.
- The Clustered, Regularly Interspaced, Short Palindromic Repeats-associated Endonuclease 9 (CRISPR/Cas9)-created MDM2 T309G Mutation Enhances Vitreous-induced Expression of MDM2 and Proliferation and Survival of Cells. J Biol Chem. 2016 07 29; 291(31):16339-47.
- Revisiting the mouse model of oxygen-induced retinopathy. Eye Brain. 2016; 8:67-79.
- Blood biomarkers in a mouse model of CADASIL. Brain Res. 2016 08 01; 1644:118-26.
- Disorders of Vascular Permeability. Annu Rev Pathol. 2016 05 23; 11:251-81.
- Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma. Am J Pathol. 2016 Apr; 186(4):1055-64.
- Endomucin prevents leukocyte-endothelial cell adhesion and has a critical role under resting and inflammatory conditions. Nat Commun. 2016 Feb 02; 7:10363.
- Coculture Assays for Endothelial Cells-Mural Cells Interactions. Methods Mol Biol. 2016; 1464:35-47.
- Characterization of cells from patient-derived fibrovascular membranes in proliferative diabetic retinopathy. Mol Vis. 2015; 21:673-87.
- From pathobiology to the targeting of pericytes for the treatment of diabetic retinopathy. Curr Diab Rep. 2015 Feb; 15(2):573.
- Lymphatics in development and pathology: introduction to a special issue of Microvascular Research. Microvasc Res. 2014 Nov; 96:1-2.
- Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration. Pathology. 2014 Aug; 46(5):416-23.
- Retinal microangiopathy in a mouse model of inducible mural cell loss. Am J Pathol. 2014 Oct; 184(10):2618-26.
- Notch signaling functions in retinal pericyte survival. Invest Ophthalmol Vis Sci. 2014 Jul 11; 55(8):5191-9.
- Tamoxifen toxicity in cultured retinal pigment epithelial cells is mediated by concurrent regulated cell death mechanisms. Invest Ophthalmol Vis Sci. 2014 Jul 03; 55(8):4747-58.
- Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas. Lab Invest. 2014 Jul; 94(7):752-65.
- The role of shear-induced transforming growth factor-ß signaling in the endothelium. Arterioscler Thromb Vasc Biol. 2013 Nov; 33(11):2608-17.
- Epoxyeicosanoids promote organ and tissue regeneration. Proc Natl Acad Sci U S A. 2013 Aug 13; 110(33):13528-33.
- Vascular endothelial growth factor is important for brown adipose tissue development and maintenance. FASEB J. 2013 Aug; 27(8):3257-71.
- All vessels are not created equal. Am J Pathol. 2013 Apr; 182(4):1087-91.
- NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013 Jan 07; 54(1):110-20.
- Transcriptional repression of VEGF by ZNF24: mechanistic studies and vascular consequences in vivo. Blood. 2013 Jan 24; 121(4):707-15.
- Expression and role of VEGF--a in the ciliary body. Invest Ophthalmol Vis Sci. 2012 Nov 07; 53(12):7520-7.
- A brief history of anti-VEGF for the treatment of ocular angiogenesis. Am J Pathol. 2012 Aug; 181(2):376-9.
- The maintenance of lymphatic vessels in the cornea is dependent on the presence of macrophages. Invest Ophthalmol Vis Sci. 2012 May 31; 53(6):3145-53.
- Molecular regulation of vascular endothelial growth factor expression in the retinal pigment epithelium. Mol Vis. 2012; 18:519-27.
- Role of shear-stress-induced VEGF expression in endothelial cell survival. J Cell Sci. 2012 Feb 15; 125(Pt 4):831-43.
- Forty-year journey of angiogenesis translational research. Sci Transl Med. 2011 Dec 21; 3(114):114rv3.
- Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J Clin Invest. 2012 Jan; 122(1):178-91.
- Expression and role of VEGF in the adult retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2011 Dec 09; 52(13):9478-87.
- Heat treatment of retinal pigment epithelium induces production of elastic lamina components and antiangiogenic activity. FASEB J. 2012 Feb; 26(2):567-75.
- Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development. Dev Biol. 2011 Oct 01; 358(1):9-22.
- TGF-ß signaling is required for maintenance of retinal ganglion cell differentiation and survival. Neuroscience. 2011 Aug 25; 189:123-31.
- The role of RPE cell-associated VEGF189 in choroidal endothelial cell transmigration across the RPE. Invest Ophthalmol Vis Sci. 2011 Jan; 52(1):570-8.
- Signal transduction in vasculogenesis and developmental angiogenesis. Int J Dev Biol. 2011; 55(4-5):353-63.
- Differential effects of VEGFR-1 and VEGFR-2 inhibition on tumor metastases based on host organ environment. Cancer Res. 2010 Nov 01; 70(21):8357-67.
- RhoA/ROCK signaling is essential for multiple aspects of VEGF-mediated angiogenesis. FASEB J. 2010 Sep; 24(9):3186-95.
- Editorial. Microvasc Res. 2010 May; 79(3):161.
- Intracellular thiol redox status regulates lymphangiogenesis and dictates corneal limbal graft survival. Invest Ophthalmol Vis Sci. 2010 May; 51(5):2450-8.
- An essential role for RPE-derived soluble VEGF in the maintenance of the choriocapillaris. Proc Natl Acad Sci U S A. 2009 Nov 03; 106(44):18751-6.
- The function of vascular endothelial growth factor. Biofactors. 2009 Jul-Aug; 35(4):332-7.
- Inhibition of VEGF or TGF-{beta} signaling activates endothelium and increases leukocyte rolling. Arterioscler Thromb Vasc Biol. 2009 Aug; 29(8):1185-92.
- TGF-beta is required for vascular barrier function, endothelial survival and homeostasis of the adult microvasculature. PLoS One. 2009; 4(4):e5149.
- Seminars in Ophthalmology. Editorial. Semin Ophthalmol. 2009 Mar-Apr; 24(2):50-1.
- Endogenous VEGF is required for visual function: evidence for a survival role on müller cells and photoreceptors. PLoS One. 2008; 3(11):e3554.
- Arterial versus venous endothelial cells. Cell Tissue Res. 2009 Jan; 335(1):5-16.
- Role of cell and matrix-bound VEGF isoforms in lens development. Invest Ophthalmol Vis Sci. 2009 Jan; 50(1):311-21.
- Is blockade of vascular endothelial growth factor beneficial for all types of diabetic retinopathy? Diabetologia. 2008 Sep; 51(9):1570-3.
- IGF2: epigenetic regulation and role in development and disease. Cytokine Growth Factor Rev. 2008 Apr; 19(2):111-20.
- Tumor escape from endogenous, extracellular matrix-associated angiogenesis inhibitors by up-regulation of multiple proangiogenic factors. Clin Cancer Res. 2008 Mar 01; 14(5):1529-39.
- VEGF and TGF-beta are required for the maintenance of the choroid plexus and ependyma. J Exp Med. 2008 Feb 18; 205(2):491-501.
- The role of hypoxia in vascular injury and repair. Annu Rev Pathol. 2008; 3:615-43.
- Judah Folkman's contribution to the inhibition of angiogenesis. Lymphat Res Biol. 2008; 6(3-4):203-7.
- Pericyte isolation and use in endothelial/pericyte coculture models. Methods Enzymol. 2008; 443:315-31.
- Coordinated vascular endothelial growth factor expression and signaling during skeletal myogenic differentiation. Mol Biol Cell. 2008 Mar; 19(3):994-1006.
- Repression of vascular endothelial growth factor expression by the zinc finger transcription factor ZNF24. Cancer Res. 2007 Sep 15; 67(18):8736-41.
- What tangled webs they weave: Rho-GTPase control of angiogenesis. Cell Mol Life Sci. 2007 Aug; 64(16):2053-65.
- Vascular endothelial cell growth factor-a: not just for endothelial cells anymore. Am J Pathol. 2007 Jul; 171(1):14-8.
- Contextual role for angiopoietins and TGFbeta1 in blood vessel stabilization. J Cell Sci. 2007 May 15; 120(Pt 10):1810-7.
- Roles for VEGF in the adult. Microvasc Res. 2007 Sep-Nov; 74(2-3):100-13.
- Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing. Am J Pathol. 2007 Apr; 170(4):1178-91.
- Wnt1 and Wnt5a affect endothelial proliferation and capillary length; Wnt2 does not. Growth Factors. 2007 Feb; 25(1):25-32.
- Breast cancer cells secreted platelet-derived growth factor-induced motility of vascular smooth muscle cells is mediated through neuropilin-1. Mol Carcinog. 2006 Nov; 45(11):871-80.
- Cultured endothelial cells display endogenous activation of the canonical Wnt signaling pathway and express multiple ligands, receptors, and secreted modulators of Wnt signaling. Dev Dyn. 2006 Nov; 235(11):3110-20.
- VEGF expression and receptor activation in the choroid during development and in the adult. Invest Ophthalmol Vis Sci. 2006 Jul; 47(7):3135-42.
- Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med. 2006 Jun; 12(6):642-9.
- Proceedings of the Third International Symposium on Retinopathy of Prematurity: an update on ROP from the lab to the nursery (November 2003, Anaheim, California). Mol Vis. 2006 May 23; 12:532-80.
- Vascular endothelial growth factor localization in the adult. Am J Pathol. 2006 Feb; 168(2):639-48.
- Development of the endothelium. Handb Exp Pharmacol. 2006; (176 Pt 1):71-105.
- Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest. 2005 Sep; 115(9):2363-72.
- Analysis of hypoxia-related gene expression in sarcomas and effect of hypoxia on RNA interference of vascular endothelial cell growth factor A. Cancer Res. 2005 Jul 01; 65(13):5881-9.
- Engineering vascularized skeletal muscle tissue. Nat Biotechnol. 2005 Jul; 23(7):879-84.
- CADASIL mutations impair Notch3 glycosylation by Fringe. Hum Mol Genet. 2005 Jun 15; 14(12):1631-9.
- Transcriptional regulation of vascular endothelial growth factor in cancer. Cytokine Growth Factor Rev. 2005 Feb; 16(1):77-89.
- ErbB2 overexpression in mammary cells upregulates VEGF through the core promoter. Biochem Biophys Res Commun. 2005 Jan 14; 326(2):455-65.
- VEGF 164 governs leukocyte dynamics and pathological neovascularization. IOVS. 2005.
- Expression of ld 1 protein in developing retinal vasculature. IOVS. 2005.
- Detection of circulating endothelial precursor cells by in vivo flow cytometry. IOVS. 2005.
- Functional analysis of a mutant form of the receptor tyrosine kinase Tie2 causing venous malformations. J Mol Med (Berl). 2005 Jan; 83(1):58-63.
- Endothelial-mesenchymal interactions in vitro reveal molecular mechanisms of smooth muscle/pericyte differentiation. Stem Cells Dev. 2004 Oct; 13(5):509-20.
- Identification of genes involved in VEGF-mediated vascular morphogenesis using embryonic stem cell-derived cystic embryoid bodies. Lab Invest. 2004 Sep; 84(9):1209-18.
- Endothelial cell-astrocyte interactions and TGF beta are required for induction of blood-neural barrier properties. Brain Res Dev Brain Res. 2004 Aug 18; 152(1):25-38.
- VEGF expression is downregulated in nitrofen-induced congenital diaphragmatic hernia. J Pediatr Surg. 2004 Jun; 39(6):825-8; discussion 825-8.
- VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest. 2004 Apr; 113(7):1040-50.
- Culture of large vessel endothelial cells on floating collagen gels promotes a phenotype characteristic of endothelium in vivo. Differentiation. 2004 Apr; 72(4):162-70.
- Development and pathology of the hyaloid, choroidal and retinal vasculature. Int J Dev Biol. 2004; 48(8-9):1045-58.
- Pericyte production of cell-associated VEGF is differentiation-dependent and is associated with endothelial survival. Dev Biol. 2003 Dec 01; 264(1):275-88.
- Retinal pigment epithelium and endothelial cell interaction causes retinal pigment epithelial barrier dysfunction via a soluble VEGF-dependent mechanism. Exp Eye Res. 2003 Nov; 77(5):593-9.
- VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J Exp Med. 2003 Aug 04; 198(3):483-9.
- Getting Tie(2)d up in angiogenesis. J Clin Invest. 2002 Dec; 110(11):1615-7.
- Won't you be my neighbor? Local induction of arteriogenesis. Cell. 2002 Aug 09; 110(3):289-92.
- Defective pulmonary development in the absence of heparin-binding vascular endothelial growth factor isoforms. Am J Respir Cell Mol Biol. 2002 Aug; 27(2):194-203.
- Tales of the cryptic: unveiling more angiogenesis inhibitors. Trends Mol Med. 2002 Jul; 8(7):313-5.
- Skeletal defects in VEGF(120/120) mice reveal multiple roles for VEGF in skeletogenesis. Development. 2002 Apr; 129(8):1893-904.
- Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest. 2002 Feb; 109(3):327-36.
- Wnt signaling in the vasculature. Angiogenesis. 2002; 5(1-2):1-9.
- Differential expression of VEGF isoforms in mouse during development and in the adult. Dev Dyn. 2001 Feb; 220(2):112-21.
- TGF beta is required for the formation of capillary-like structures in three-dimensional cocultures of 10T1/2 and endothelial cells. Angiogenesis. 2001; 4(1):11-20.
- Cell-cell interactions in vascular development. Curr Top Dev Biol. 2001; 52:107-49.
- Therapeutic angiogenesis for cardiovascular disease. Curr Control Trials Cardiovasc Med. 2001; 2(6):278-285.
- Cellular interactions in vascular growth and differentiation. Int Rev Cytol. 2001; 204:1-48.
- Kissing cousins-evidence for a common vascular cell precursor. Nat Med. 2000 Dec; 6(12):1323-4.
- Release of bFGF, an endothelial cell survival factor, by osmotic shock. Invest Ophthalmol Vis Sci. 1999 Nov; 40(12):2945-51.
- A secreted frizzled related protein, FrzA, selectively associates with Wnt-1 protein and regulates wnt-1 signaling. J Cell Sci. 1999 Nov; 112 ( Pt 21):3815-20.
- Vascular endothelial growth factor-induced migration of vascular smooth muscle cells in vitro. Microvasc Res. 1999 Sep; 58(2):128-36.
- Identification and cloning of a secreted protein related to the cysteine-rich domain of frizzled. Evidence for a role in endothelial cell growth control. Circ Res. 1999 Jun 25; 84(12):1433-45.
- Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Nat Med. 1999 May; 5(5):495-502.
- Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ Res. 1999 Feb 19; 84(3):298-305.
- Blood vessel maturation: vascular development comes of age. J Clin Invest. 1999 Jan; 103(2):157-8.
- Functional and biochemical interactions of Wnts with FrzA, a secreted Wnt antagonist. Development. 1998 Dec; 125(23):4767-76.
- PDGF, TGF-beta, and heterotypic cell-cell interactions mediate endothelial cell-induced recruitment of 10T1/2 cells and their differentiation to a smooth muscle fate. J Cell Biol. 1998 May 04; 141(3):805-14.
- Cell-cell interactions in vessel assembly: a model for the fundamentals of vascular remodelling. Transpl Immunol. 1997 Sep; 5(3):177-8.
- Vascular development: cellular and molecular regulation. FASEB J. 1997 Apr; 11(5):365-73.
- Control of angiogenesis by the pericyte: molecular mechanisms and significance. EXS. 1997; 79:419-28.
- Blood vessel formation: what is its molecular basis? Cell. 1996 Dec 27; 87(7):1153-5.
- Elevated levels of basic fibroblast growth factor in patients with limb ischemia. Am Heart J. 1996 Nov; 132(5):1015-9.
- Pericytes in the microvasculature. Cardiovasc Res. 1996 Oct; 32(4):687-98.
- Vascular endothelial growth factor and its receptors. Cytokine Growth Factor Rev. 1996 Oct; 7(3):259-70.
- Beta-chemokine TCA3 binds to and activates rat vascular smooth muscle cells. J Immunol. 1996 Sep 01; 157(5):2143-8.
- Comparison of the effects of mechanical stimulation on venous and arterial smooth muscle cells in vitro. J Vasc Res. 1996 Sep-Oct; 33(5):405-13.
- Tumor angiogenesis: a physiological process or genetically determined? Cancer Metastasis Rev. 1996 Jun; 15(2):205-12.
- Cloning and mRNA expression of vascular endothelial growth factor in ischemic retinas of Macaca fascicularis. Invest Ophthalmol Vis Sci. 1996 Jun; 37(7):1334-40.
- The mouse gene for vascular endothelial growth factor. Genomic structure, definition of the transcriptional unit, and characterization of transcriptional and post-transcriptional regulatory sequences. J Biol Chem. 1996 Feb 16; 271(7):3877-83.
- Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch Ophthalmol. 1996 Jan; 114(1):66-71.
- Basic fibroblast growth factor increases nitric oxide synthase production in bovine endothelial cells. Am J Physiol. 1995 Nov; 269(5 Pt 2):H1583-9.
- Hypoxic induction of vascular endothelial growth factor (VEGF) in human epithelial cells is mediated by increases in mRNA stability. FEBS Lett. 1995 Aug 21; 370(3):203-8.
- Regulation of basic fibroblast growth factor (bFGF) gene and protein expression following its release from sublethally injured endothelial cells. J Cell Biochem. 1995 Jul; 58(3):328-43.
- Alterations in gene expression associated with changes in the state of endothelial differentiation. Differentiation. 1995 Feb; 58(3):217-26.
- Hypoxic induction of endothelial cell growth factors in retinal cells: identification and characterization of vascular endothelial growth factor (VEGF) as the mitogen. Mol Med. 1995 Jan; 1(2):182-93.
- Mechanisms of retinal and choroidal neovascularization. Invest Ophthalmol Vis Sci. 1994 Nov; 35(12):3974-9.
- Comparative toxicity of mitomycin C and 5-fluorouracil in vitro. Am J Ophthalmol. 1994 Sep 15; 118(3):332-7.
- Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol. 1994 Sep; 145(3):574-84.
- Arachidonic acid metabolites in bFGF-, PDGF-, and serum-stimulated vascular cell growth. Exp Cell Res. 1994 Jun; 212(2):262-73.
- Elevated basic fibroblast growth factor in the serum of patients with Duchenne muscular dystrophy. Ann Neurol. 1994 Mar; 35(3):362-5.
- Optic nerve injury alters basic fibroblast growth factor localization in the retina and optic tract. J Neurosci. 1994 Mar; 14(3 Pt 2):1441-9.
- Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 1994 Jan; 35(1):101-11.
- Comparison of normal and tumorigenic endothelial cells: differences in thrombospondin production and responses to transforming growth factor-beta. J Cell Sci. 1994 Jan; 107 ( Pt 1):39-46.
- Neuroprotective effect of chronic infusion of basic fibroblast growth factor on seizure-associated hippocampal damage. Brain Res. 1993 Oct 29; 626(1-2):335-8.
- Density-dependent endothelial cell production of an inhibitor of smooth muscle cell growth. J Cell Biochem. 1993 Sep; 53(1):21-31.
- Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem Biophys Res Commun. 1993 Jun 15; 193(2):631-8.
- Growth factor effects on cells of the vascular wall: a survey. Growth Factors. 1993; 8(1):61-75.
- Cell-cell interactions in diabetic angiopathy. Diabetes Care. 1992 Sep; 15(9):1168-80.
- The location and expression of fibroblast growth factor (FGF) in F9 visceral and parietal embryonic cells after retinoic acid-induced differentiation. Differentiation. 1992 Aug; 50(3):141-52.
- An in vitro model for cell-cell interactions. In Vitro Cell Dev Biol. 1992 Jul-Aug; 28A(7-8):521-8.
- Rapid fibroblast growth factor-induced increases in protein phosphorylation and ornithine decarboxylase activity: regulation by heparin and comparison to nerve growth factor-induced increases. Exp Cell Res. 1992 Jul; 201(1):154-9.
- Capillary growth: a two-cell system. Semin Cancer Biol. 1992 Apr; 3(2):49-56.
- Mechanisms of endothelial growth control. Am J Respir Cell Mol Biol. 1992 Jan; 6(1):1-8.
- Alterations in endothelial superoxide dismutase levels as a function of growth state in vitro. Invest Ophthalmol Vis Sci. 1992 Jan; 33(1):36-41.
- Endothelial cell regulation by transforming growth factor-beta. J Cell Biochem. 1991 Nov; 47(3):224-9.
- Sustained-release endotoxin. A model for inducing corneal neovascularization. Invest Ophthalmol Vis Sci. 1991 Oct; 32(11):2906-11.
- Density-dependent expression of hyaluronic acid binding to vascular cells in vitro. Microvasc Res. 1991 Mar; 41(2):239-51.
- Retinol-induced modification of the extracellular matrix of endothelial cells: its role in growth control. In Vitro Cell Dev Biol. 1991 Feb; 27A(2):151-7.
- Regulators of angiogenesis. Annu Rev Physiol. 1991; 53:217-39.
- FGF and TGF-beta: actions and interactions in biological systems. Crit Rev Eukaryot Gene Expr. 1991; 1(3):157-72.
- Modes of FGF release in vivo and in vitro. Cancer Metastasis Rev. 1990 Nov; 9(3):227-38.
- Nerve growth factor and fibroblast growth factor regulate neurite outgrowth and gene expression in PC12 cells via both protein kinase C- and cAMP-independent mechanisms. J Cell Biol. 1990 Apr; 110(4):1333-9.
- Heparin-endothelial cell interactions. Haemostasis. 1990; 20 Suppl 1:159-65.
- Heparin-mediated release of fibroblast growth factor-like activity into the circulation of rabbits. Growth Factors. 1990; 3(3):221-9.
- Influence of pericytes on capillary endothelial cell growth. Am Rev Respir Dis. 1989 Oct; 140(4):1129-31.
- Growth factors are released by mechanically wounded endothelial cells. J Cell Biol. 1989 Aug; 109(2):811-22.
- An activated form of transforming growth factor beta is produced by cocultures of endothelial cells and pericytes. Proc Natl Acad Sci U S A. 1989 Jun; 86(12):4544-8.
- Expression of fibroblast growth factor by F9 teratocarcinoma cells as a function of differentiation. J Cell Biol. 1989 Jun; 108(6):2467-76.
- Acidic fibroblast growth factor enhances peripheral nerve regeneration in vivo. Plast Reconstr Surg. 1989 Jun; 83(6):1013-9; discussion 1020-1.
- Importance of size, sulfation, and anticoagulant activity in the potentiation of acidic fibroblast growth factor by heparin. J Biol Chem. 1989 Apr 25; 264(12):6892-7.
- Heparin potentiates the action of acidic fibroblast growth factor by prolonging its biological half-life. J Cell Physiol. 1989 Feb; 138(2):221-6.
- Heparin and growth control of vascular cells. Ann N Y Acad Sci. 1989; 556:255-67.
- Acidic fibroblast growth factor stimulates adrenal chromaffin cells to proliferate and to extend neurites, but is not a long-term survival factor. Neuron. 1988 Nov; 1(9):783-90.
- Characterization of vascular development in the mouse retina. Microvasc Res. 1988 Nov; 36(3):275-90.
- Sulfated glycosaminoglycans modify growth factor-induced neurite outgrowth in PC12 cells. J Cell Physiol. 1988 May; 135(2):293-300.
- Preferential expression of a 130,000-Da cell surface protein by vascular wall cells in vitro and in vivo. Microvasc Res. 1988 May; 35(3):265-77.
- Acidic fibroblast growth factor enhances regeneration of processes by postnatal mammalian retinal ganglion cells in culture. Proc Natl Acad Sci U S A. 1988 Apr; 85(7):2388-92.
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Endomucin as a Novel regulator of Angiogenesis
The studies aim to determine the contribution of endomucin, an endothelial-specific cell surface proteoglycan, to pathologic angiogenesis and to understanding the mechanism by which endomucin regulates VEGFR2 signaling. Clinical application: Novel target for blocking pathologic neovascularization
Endomucin as a Regulator of Vascular Inflammation
Cell surface endomucin normally blocks endothelial cell-leukocyte interactions. Under inflammatory conditions, endomucin is shed, facilitating these interactions. Dr. D’Amore is investigating the mechanisms by which endomucin blocks leukocyte adhesion as well the molecular basis of its shedding from the cell surface. Clinical application: Suppression of ocular inflammation
Repurposing Troglitazone to Protect Retinal Pigment Epithelium
Dr. D’Amore, in collaboration with Dr. Eric Ng, have demonstrated that troglitazone can protect RPE from damage/death due to oxidized LDL. They are investigating the mechanisms of this protection and developing novel analogs. Clinical application: Prevention or attenuation of dry AMD
Lipid Handling by RPE: Effects of Aging and MicroRNAs
Dr. D’Amore’s group is examining the effect of aging on the expression of genes central to the normal handling of lipids by RPE, including ABCA1, SRB1 and CD36, to name a few. They are also investigating the regulation of these genes by specific miRNAs. Clinical application: Pathogenesis of AMD
Molecular Bases of the Eye Disease
The goal of this project is to train the next generation of scientists who will address the problems of eye disease by identifying new means of diagnosis, prevention and treatment.
Current Members of Dr. Patricia D’Amore’s Laboratory
Administrative Coordinator
- Erin Porter
Laboratory Manager
- Kahira Saez-Torres
Postdoctoral Fellows
- Michelle LeBlanc, PhD
- Zhengping Hu, PhD
Technician
- Issahy Cano
Alumni
More than 60 trainees have worked in Dr. D’Amore’s laboratory.
Below is a Q&A with Dr. D'Amore...
You study the vasculature. Can you describe it?
The vasculature can be compared to a plumbing system, with the heart as the major pump and the blood vessels as the pipes that supply all parts of the body. The architecture of blood vessels is like a tree, with the central trunk called the aorta, and the smallest branches called capillaries. It is at the capillary level that oxygen and nutrients diffuse out of the blood to nourish the tissues.
The term angiogenesis is in the news a lot. What does angiogenesis mean?
Angiogenesis comes from the terms “angio,” meaning blood, and “genesis” meaning birth. So angiogenesis is the growth of new blood vessels, specifically the smallest blood vessels (capillaries).
Why is there so much interest in angiogenesis?
Angiogenesis has become a topic of interest because of its central role in tumor growth. All tissues, including tumors, require a vascular supply to deliver oxygen and nutrients, and to remove CO2 and toxins. In the early 1970s, Judah Folkman at Children’s Hospital in Boston hypothesized that tumor growth could be prevented by blocking the growth of blood vessels into tumors. More importantly, most blood vessels in the adult are not growing, so it should be possible to develop therapies that target only the blood vessels growing into the tumors. With this, the idea of anti-angiogenic therapy was born.
On the other hand, there are diseases that are characterized by insufficient blood flow. Coronary artery disease—in which the vessels that nourish the heart are blocked—is a very common example. In this case, the goal would be to stimulate the growth of new blood vessels that could circumvent the blocked arteries. Therapies aimed at growing new blood vessels are called pro-angiogenic
How does anti-angiogenic therapy differ from the standard tumor treatments?
Conventional anti-cancer treatment has generally used chemotherapy. This type of treatment uses relatively non-specific agents that target growing cells. Though tumors cells would most certainly be killed by this treatment, it also destroys other dividing cells such as hair follicles (which is why patients lose their hair), the cells that line the stomach (which is the cause of the nausea), and the blood-forming cells of the bone marrow (which is why people can become anemic, or have reduced numbers of white cells). In contrast, the anti-angiogenic therapies should target only the growing blood vessels, and therefore, should have significantly fewer side effects.
Another very important difference between conventional chemotherapy and anti-angiogenic therapy is that patients often develop “resistance” to specific chemotherapies. Resistance develops when a subset of tumor cells acquires the ability to continue to grow in the presence of the chemotherapeutic agent. When this happens the tumor stops responding to the therapy and continues to grow; that is, the tumor becomes “resistant.” Different chemotherapies can be used, but eventually the tumor develops a resistance to each one and the physician runs out of treatment options. This resistance is avoided by targeting the blood vessels instead of the tumor cells.
What does angiogenesis have to do with eye disease?
New blood-vessel growth is a complication of a number of common eye diseases, including very common pathologies, such as diabetic retinopathy and the wet form of macular degeneration. In both of these cases, new blood vessels grow in places where they normally should not. Furthermore, these new blood vessels are very leaky, and as a result, fluid can accumulate and disrupt vision.
Do tumor angiogenesis and eye angiogenesis have anything in common?
They have quite a bit in common. Perhaps not surprisingly, nature is very economical and uses the same molecules and mechanisms in many settings. A protein called vascular endothelial growth factor (VEGF) has been shown to be involved in both tumor angiogenesis and the angiogenesis associated with diabetic retinopathy and macular degeneration.
Are there any anti-angiogenic therapies available now?
The first anti-angiogenic therapy for cancer, called Avastin (made by Genentech), was approved for the treatment of colorectal cancer (in combination with chemotherapy) by the FDA. This drug is an antibody that can bind to VEGF and thereby block its action. The clinical trials that preceded its approval showed that, when used in combination with chemotherapy, it led to a four-month increase in survival when compared to chemotherapy alone. Since that time, a number of trials have been conducted to assess its effectiveness against other kinds of cancer.
Encouraged by the promising results against cancer, and knowing that VEGF had been shown to play a role in angiogenesis in the eye, ophthalmologists began to treat their patients with wet macular degeneration with Avastin—first intravenously and later by injection into the eye. Today, several anti-angiogenic therapies, including Lucentis and Eylea, have been FDA-approved for neovascular eye diseases.
You mentioned pro-angiogenesis. Is there any on-going work to develop pro-angiogenic therapies?
Investigators are developing methods to deliver the angiogenic factor VEGF to tissues that need new blood vessels. This is being done for heart disease, as well as for conditions where patients have insufficient blood flow to their legs (also called peripheral vascular disease