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Kip Connor, Ph.D.

TitleAssistant Professor of Ophthalmology
InstitutionMassachusetts Eye and Ear Infirmary
DepartmentOphthalmology
AddressMassachusetts Eye & Ear Infrm
Ophthalmology
243 Charles St
Boston MA 02114

 Mentoring 
 current student opportunities
Available: 09/01/13, Expires: 09/07/14

Retinal detachment and subsequent neurodegeneration of the retina continues to be a leading cause of visual impairment resulting from ocular trauma. Photoreceptor apoptosis is a major cause of visual loss in retinal detachment (RD). However, the underlying processes that facilitate this have remained elusive. This project aims to identify the initiating factors involved in photoreceptor cell death (retinal degeneration) in response to traumatic retinal detachment. This study is innovative in that it will begin to define the initiating factors involved in retinal neurodegeneration, a common cause of vision loss. When photoreceptor degeneration occurs it tends to correlate to a rise in immune activity. One possibility is that the immune system is mounting a response against the photoreceptors in the damaged retina to specifically target their removal. This can severely impact visual acuity, understanding the mechanism by which the immune system facilitates photoreceptor apoptosis in retinal detachment remains unresolved and it could be of significant therapeutic value to dampen its effects. The retina is specialized neural tissue and is commonly referred to as the “window into the brain”. Findings in this proposal will likely encompass similar mechanisms found in other neurodegenerations resulting from traumatic brain injury.

The PI and a senior fellow in the laboratory will oversee the student working on this project. They will learn how to effectively employ the mouse model of retinal detachment and utilize key transgenic animals in order to define immune mediators of retinal degeneration. Additionally, if time allows, key pharmaceutical therapeutics will be identified and utilized in vivo in order to temper neurodegeneration.

Available: 09/01/11, Expires: 06/01/14

Pathological neovascularization is a hallmark of numerous vascular diseases. Since the balance between neovessel formation and regression determines severity, modulating neovessel growth is highly desirable. Vascular regression coincides with a spike in immune activity; we therefore hypothesize (and pilot studies suggest) that pathologic vessel regression may be mediated, in part, through the complement system, an integral part of innate immunity. The complement system is an intricate immune surveillance system that is able to discriminate between healthy host tissue, diseased host tissue, apoptotic cells and foreign invaders and is able to modulate the elimination and repair of host tissue accordingly. Students will work to define the role of the complement system in a mouse model of oxygen induced retinopathy (a model for neovascular disease). Students will have to be comfortable working with animals (previous experience with mice is a plus).

 completed student projects
Characterizing the role of the complement system in vascular regression in a mouse model of retinopathy
Summer, 06/17/13 - 08/16/13

 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Adini I, Ghosh K, Adini A, Chi ZL, Yoshimura T, Benny O, Connor KM, Rogers MS, Bazinet L, Birsner AE, Bielenberg DR, D'Amato RJ. Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment. J Clin Invest. 2014 Jan 2; 124(1):425-36.
    View in: PubMed
  2. Saint-Geniez M, Jiang A, Abend S, Liu L, Sweigard H, Connor KM, Arany Z. PGC-1a Regulates Normal and Pathological Angiogenesis in the Retina. Am J Pathol. 2013 Jan; 182(1):255-65.
    View in: PubMed
  3. Yanai R, Thanos A, Connor KM. Complement involvement in neovascular ocular diseases. Adv Exp Med Biol. 2012; 946:161-83.
    View in: PubMed
  4. Sapieha P, Stahl A, Chen J, Seaward MR, Willett KL, Krah NM, Dennison RJ, Connor KM, Aderman CM, Liclican E, Carughi A, Perelman D, Kanaoka Y, Sangiovanni JP, Gronert K, Smith LE. 5-Lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of ?-3 polyunsaturated fatty acids. Sci Transl Med. 2011 Feb 9; 3(69):69ra12.
    View in: PubMed
  5. Stahl A, Sapieha P, Connor KM, Sangiovanni JP, Chen J, Aderman CM, Willett KL, Krah NM, Dennison RJ, Seaward MR, Guerin KI, Hua J, Smith LE. Short communication: PPAR gamma mediates a direct antiangiogenic effect of omega 3-PUFAs in proliferative retinopathy. Circ Res. 2010 Aug 20; 107(4):495-500.
    View in: PubMed
  6. Stahl A, Connor KM, Sapieha P, Chen J, Dennison RJ, Krah NM, Seaward MR, Willett KL, Aderman CM, Guerin KI, Hua J, Löfqvist C, Hellström A, Smith LE. The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci. 2010 Jun; 51(6):2813-26.
    View in: PubMed
  7. Connor KM, Krah NM, Dennison RJ, Aderman CM, Chen J, Guerin KI, Sapieha P, Stahl A, Willett KL, Smith LE. Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat Protoc. 2009; 4(11):1565-73.
    View in: PubMed
  8. Mammoto A, Connor KM, Mammoto T, Yung CW, Huh D, Aderman CM, Mostoslavsky G, Smith LE, Ingber DE. A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature. 2009 Feb 26; 457(7233):1103-8.
    View in: PubMed
  9. Stahl A, Connor KM, Sapieha P, Willett KL, Krah NM, Dennison RJ, Chen J, Guerin KI, Smith LE. Computer-aided quantification of retinal neovascularization. Angiogenesis. 2009; 12(3):297-301.
    View in: PubMed
  10. Adini A, Fainaru O, Udagawa T, Connor KM, Folkman J, D'Amato RJ. Matrigel cytometry: a novel method for quantifying angiogenesis in vivo. J Immunol Methods. 2009 Mar 15; 342(1-2):78-81.
    View in: PubMed
  11. Lofqvist C, Willett KL, Aspegren O, Smith AC, Aderman CM, Connor KM, Chen J, Hellstrom A, Smith LE. Quantification and localization of the IGF/insulin system expression in retinal blood vessels and neurons during oxygen-induced retinopathy in mice. Invest Ophthalmol Vis Sci. 2009 Apr; 50(4):1831-7.
    View in: PubMed
  12. Chen J, Connor KM, Aderman CM, Willett KL, Aspegren OP, Smith LE. Suppression of retinal neovascularization by erythropoietin siRNA in a mouse model of proliferative retinopathy. Invest Ophthalmol Vis Sci. 2009 Mar; 50(3):1329-35.
    View in: PubMed
  13. Chen J, Connor KM, Aderman CM, Smith LE. Erythropoietin deficiency decreases vascular stability in mice. J Clin Invest. 2008 Feb; 118(2):526-33.
    View in: PubMed
  14. Connor KM, Hempel N, Nelson KK, Dabiri G, Gamarra A, Belarmino J, Van De Water L, Mian BM, Melendez JA. Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells. Cancer Res. 2007 Nov 1; 67(21):10260-7.
    View in: PubMed
  15. Chen J, Connor KM, Smith LE. Overstaying their welcome: defective CX3CR1 microglia eyed in macular degeneration. J Clin Invest. 2007 Oct; 117(10):2758-62.
    View in: PubMed
  16. Connor KM, SanGiovanni JP, Lofqvist C, Aderman CM, Chen J, Higuchi A, Hong S, Pravda EA, Majchrzak S, Carper D, Hellstrom A, Kang JX, Chew EY, Salem N, Serhan CN, Smith LE. Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med. 2007 Jul; 13(7):868-73.
    View in: PubMed
  17. Lofqvist C, Chen J, Connor KM, Smith AC, Aderman CM, Liu N, Pintar JE, Ludwig T, Hellstrom A, Smith LE. IGFBP3 suppresses retinopathy through suppression of oxygen-induced vessel loss and promotion of vascular regrowth. Proc Natl Acad Sci U S A. 2007 Jun 19; 104(25):10589-94.
    View in: PubMed
  18. Connor, K.M., Aderman, C.M, Chen, J., Higuchi, A., SanGiovanni, J.-P., Chew, E.Y., Carper, D., Salem, N., Smith, L.E.H. Dietary omega-3 Long-Chain Polyunsaturated Fatty Acids Protect Against Pathological Retinal Neovascularization Through Modulation of Microglial Derived TNF-alpha. The Association for Research in Vision and Ophthalmology Annual Meeting. 2007.
  19. Lofqvist, C, Chen, C, Connor, K.M., Smith, A.C.H, Aderman, C.M, Liu, N, Pintar, J.E, Ludwig, T, Hellstrom, A, Smith, L.E.H. IGFBP3 suppresses retinopathy through suppression of oxygen-induced vessel loss and promotion of vascular regrowth. PNAS. 2007; 104(25):10589-94.
  20. Connor, K.M., Aderman, C.M., Chen, J., Higuchi, A., SanGiovanni, J-P., Serhan, C.N., Smith, L.E.H. . Increasing dietary omega-3 PUFA reduces pathological angiogenesis via regulation of local resolvins, protectins and TNF-alpha. Society for Free Radical Biology and Medicine 13th Annual Meeting. 2006.
  21. Dasgupta J, Subbaram S, Connor KM, Rodriguez AM, Tirosh O, Beckman JS, Jourd'Heuil D, Melendez JA. Manganese superoxide dismutase protects from TNF-alpha-induced apoptosis by increasing the steady-state production of H2O2. Antioxid Redox Signal. 2006 Jul-Aug; 8(7-8):1295-305.
    View in: PubMed
  22. Connor, K.M., Aderman, C.M, Chen, SanGiovanni, J.-P., Chew, E.Y., Carper, D., Salem, N., Smith, L.E.H. . Dietary and Pharmalogic intervention in Proliferative Retinopathy. The Association for Research in Vision and Ophthalmology Annual Meeting. 2006.
  23. Nelson KK, Subbaram S, Connor KM, Dasgupta J, Ha XF, Meng TC, Tonks NK, Melendez JA. Redox-dependent matrix metalloproteinase-1 expression is regulated by JNK through Ets and AP-1 promoter motifs. J Biol Chem. 2006 May 19; 281(20):14100-10.
    View in: PubMed
  24. Smith, L.E. and Connor, K.M. . A Radical Twist in Lipid Mediated Vascular Death. Nature Medicine. 2005; 11(12):1276-6.
  25. Smith LE, Connor KM. A radically twisted lipid regulates vascular death. Nat Med. 2005 Dec; 11(12):1275-6.
    View in: PubMed
  26. Kip M Connor. Manganese Superoxide Dismutase Regulates the Malignant Phenotype through the Production of Mitochondrial Derived Hydrogen Peroxide. 2005.
  27. Connor, K.M., Sita Subbaram, Kevin J. Regan, Kristin K. Nelson, Joseph E. Mazurkiewicz, Peter J. Bartholomew, Andrew E. Aplin, Yu-Tzu Tai, Julio Aguirre-Ghiso, Sonia C. Flores and J. Andres Melendez. Sod2-derived H2O2 Regulates the Angiogenic Phenotype via PTEN Oxidation. Journal of Biological Chemistry. 2005; 280(17):16916-24.
  28. Connor KM, Subbaram S, Regan KJ, Nelson KK, Mazurkiewicz JE, Bartholomew PJ, Aplin AE, Tai YT, Aguirre-Ghiso J, Flores SC, Melendez JA. Mitochondrial H2O2 regulates the angiogenic phenotype via PTEN oxidation. J Biol Chem. 2005 Apr 29; 280(17):16916-24.
    View in: PubMed
  29. Connor, K.M., Mazurkiewicz J.E., Melendez, J.A. . Mitochondrial-derived H2O2 mediates the cellular redistribution of phosphoinositides. Society for Free Radical Biology and Medicine 11th Annual Meeting. 2004.
  30. Connor, K.M., Regan K., Nelson, K., Goswami, P., Melendez, J.A. . Hydrogen Peroxide Regulates the PI3K Signaling Cascade via Oxidation of the Tumor Suppressor PTEN. American Association for Cancer Research. 2004.
  31. Connor, K.M., Nelson, K.K., Melendez, J.A. . Mitochondrial-derived Hydrogen Peroxide Regulates PI3K Signaling via PTEN Oxidation. Society for Free Radical Biology and Medicine 10th Annual Meeting. 2003.
  32. Connor, K.M., Nelson, K.K., Goswami, Prabat, Melendez, J.A. . Sod2-Derrived Hydrogen Peroxide Regulates the PI3K Signaling Cascade. Pathobiology of Cancer Workshop, AACR. 2003.
  33. Connor, K.M., Nelson, K.K., Regan, Kevin J., Lotz, S.A., Goswami, P., Melendez, J.A. . Potential Mechanism for the Catalase-dependent Inhibition of Tumor Growth. 9th Annual Meeting of the Oxygen Society. 2002.
  34. Connor, K.M., Rodriguez, A.M., Bennett, J.A., Melendez, J.A. . Inhibition of Tumor Growth by the expression of Mitochondrial Catalase: The Role of Hydrogen Peroxide in Regulating Caspase Activation. 8th Annual Meeting of The Oxygen Society. 2001.
  35. Cheng YC, Grill S, Derse D, Chen JY, Caradonna SJ, Connor K. Mode of action of phosphonoformate as an anti-herpes simplex virus agent. Biochim Biophys Acta. 1981 Jan 29; 652(1):90-8.
    View in: PubMed
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