The Faculty of Medicine of Harvard University Format for the Curriculum Vitae

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1 The Faculty of Medicine of Harvard University Format for the Curriculum Vitae Date Prepared: May 25, 2018 Name: Yoko Okunuki Education: 2003 MD Medicine Tokyo Medical University 2007 PhD Ophthalmology (Masahiko Usui and Tomohiro Kato) Tokyo Medical University and Department of Clinical Proteomics, Institute of Medical Science, St. Marianna University Postdoctoral Training: Fellowship Ophthalmology (Hiroshi Goto) Tokyo Medical University 04/2014- present Senior Research Fellow Ophthalmology (Kip M Connor) MEE Faculty Academic Appointments: 04/09-03/11 Assistant Lecturer Medicine (Ophthalmology) Tokyo Medical University Hachioji Medical Center 04/11-04/16 Assistant Lecturer Medicine (Ophthalmology) Tokyo Medical University Appointments at Hospitals/Affiliated Institutions 04/14- present Senior Research Fellow Ophthalmology MEE Editorial Activities: Ad hoc Reviewer Ophthalmology American Journal of Ophthalmology British Journal of Ophthalmology Molecular Vision Managed by the Office for Faculty Affairs Harvard Medical School Gordon Hall, Suite Shattuck Street, Boston, Massachusetts Updated October

2 Clinical Ophthalmology BMC Ophthalmology Medical Science Monitor Ocular Immunology and Inflammation International Journal of Ophthalmology Acta Ophthalmologica Awards and Honors: 2009 Young Researcher s Tokyo Medical University Research Award Alumni Association 2009 Medical Research Tokyo Medical University Medical Research Award Association 2010 Sasa Memorial Award Tokyo Medical University Research 2010 Experimental Eye Elsevier Research Research Top Cited Article Award 2011 Encouragement Award Japanese Ocular Inflammation Research Society 2012 Alumni Association Award Tokyo Medical University Alumni Association of Ophthalmology Research and clinical contribution 2014 MEEI/BJL Vitreoretinal Bausch & Lomb Research fellowship Research Fellowship 2016 Global Ophthalmology Awards from Bayer (Research Award) Bayer Research Report of Funded and Unfunded Projects Funding Information: Past 2007 Role of mast cells in experimental autoimmune uveitis Tokyo Medical University Research Grant The aim of this study is to evaluate the role of mast cells in experimental autoimmune uveitis using mast cell-deficient mice Proteomic analysis of disease-specific autoantibodies in Behcet's disease Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientist B The major goal of this study is to perform a comprehensive detection of autoantibodies against retinal antigens in Behcet s disease with uveitis, and evaluate their association with clinical features Immunological research for new therapeutic approaches and investigation of disease mechanisms of autoimmune uveitis Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientist B

3 The overarching goal of this study is to evaluate the association of disease activity and treatment effect by measuring cytokine production by peripheral blood mononuclear cells in patients with autoimmune uveitis Investigation of new therapeutic approaches for patients with autoimmune uveitis Japan Foundation for Applied Enzymology, Research Grant for Investigation of Etiology and Pathophysiology of Systemic Inflammatory Diseases The major goal of the study is to investigate anti-inflammatory effect of anti-hypertensive and anti-diabetes medicines in experimental autoimmune uveitis, and to evaluate their use in treating autoimmune uveitis in patients Immunological investigation for estimation of disease activity in Vogt-Koyanagi-Harada disease Tokyo Medical University, Research Grant The goal of this study is to predict disease activity before initiation of treatment in Vogt- Koyanagi-Harada disease by analyzing cytokine production from peripheral blood mononuclear cells (2016) Immunological investigation for estimation of disease activity in Vogt-Koyanagi-Harada disease Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C) The goal of this study is to predict disease activity before initiation of treatment in Vogt- Koyanagi-Harada disease by analyzing cytokine production from peripheral blood mononuclear cells This project was discontinued in 2014 due to the principal investigator (Yoko Okunuki) s relocation. Clinical Supervisory and Training Responsibilities: Uveitis/5 th year medical students/ Tokyo Medical University Supervision of clinical fellows/ Tokyo Medical University One 30 minute lecture per week for 1 year Daily Laboratory and Other Research Supervisory and Training Responsibilities: Teaching basic experiment methods for graduate students in ophthalmology Several hours/week Report of Regional, National and International Invited Teaching and Presentations as much as you can Those presentations below sponsored by outside entities are so noted and the sponsor(s) is (are) identified Regional 2008 Uveitis: Basics of observation, diagnosis and treatments/symposium for Young Researchers 3

4 Tokyo, Japan 2008 Proteomic analysis of autoantigenic retinal proteins /Final research report symposium of the research projects for private universities supported by Ministry of Education Tokyo, Japan 2013 Diagnosis of Uveitis/Macular Image Conference Tokyo, Japan (Pfizer) National 2010 Investigation of new therapeutic approaches for patients with autoimmune uveitis Funding report presentation, Japan Foundation for Applied Enzymology Tokyo, Japan 2012 Comprehensive analysis of autoantigens in endogenous uveitis by a proteomic approach Encouragement Award Lecture, Japan Ocular Inflammation Society Yokohama, Japan 2013 Molecules and genes associated with immunosuppression in ocular inflammation: Update Symposium, The 116 th annual meeting of the Japan Ophthalmological Society Tokyo, Japan International 2011 Cytokine analysis and visual prognosis of Vogt-Koyanagi-Harada disease (Workshop) The 11th international ocular inflammation society congress and international assembly of ocular inflammation society. Goa, India Report of Clinical Activities and Innovations Current Licensure and Certification: 2003 Nationally Registered Medical Doctor s License in Japan 2009 Board Certification in Japanese Ophthalmology Society 2010 License of photodynamic therapy Practice Activities: : Full time clinical duty as an ophthalmologist in Tokyo Medical University Hospital including outpatient, inpatient, and surgery. Report of Scholarship Peer-Reviewed Scholarship in print or other media: 4

5 Research Investigations 1. Takeuchi A, Usui Y, Takeuchi M, Hattori T, Kezuka T, Suzuki J, Okunuki Y, Iwasaki T, Haino M, Matsushima K, Usui M. CCR5-deficient mice develop experimental autoimmune uveoretinitis in the context of a deviant effector response. Invest Ophthalmol Vis Sci 2005;46: Usui Y, Okunuki Y, Hattori T, Takeuchi M, KezukaT, Goto H, Usui M. Expression of Costimulatory Molecules on Human Retinoblastoma Cells Y-79: Invest Ophthalmol Vis Sci 2006;47: Takeuchi M, Keino H, Suzuki J, Usui Y, Hattori T, Takeuchi A, Oh-I K, Okunuki Y, Kezuka T, Usui M. Possibility of inducing anterior chamber-associated immune deviation by TGF-beta2 treatment of monocytes isolated from Behcet's patients. Exp Eye Res 2006;83: Takeuchi M, Oh-I K, Suzuki J, Hattori T, Takeuchi A, Okunuki Y, Usui Y, Usui M. Elevated serum levels of CXCL9/monokine induced by interferon-gamma and CXCL10/interferon-gamma-inducible protein-10 in ocular sarcoidosis. Invest Ophthalmol Vis Sci 2006;47: Usui Y, Akiba H, Takeuchi M, Kezuka T, Takeuchi A, Hattori T, Okunuki Y, Yamazaki T, Yagita H, Usui M, Okumura K. The role of the ICOS/B7RP-1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis. Eur J Immunol 2006;36: Okunuki Y, Usui Y, Takeuchi M, Kezuka T, Hattori T, Masuko K, Nakamura H, Yudoh K, Usui M, Nishioka K, Kato T. Proteomic surveillance of autoimmunity in Behcet's disease with uveitis: Selenium binding protein is a novel autoantigen in Behcet's disease. Exp Eye Res 2007,84: Okunuki Y, Takeuchi M, Kezuka T, Goto H. Serum anti-alpha-enolase antibody levels in patients with uveitis secondary to Behget disease. Japanese Review of Clinical Ophthalmology. 2007;101: (Japanese) 8. Hattori T, Usui Y, Okunuki Y, Sonoda Y, Usui M, Takada E, Mizuguchi J, Yagita H, Okumura K, Akiba H, Takeuchi M. Blockade of the OX40 ligand prolongs corneal allograft survival. Eur J Immunol 2007;37: Usui Y*, Okunuki Y*, Hattori T, Kezuka T, Keino H, Ebihara N, Sugita S, Usui M, Goto H, Takeuchi M. Functional expression of B7H1 on retinal pigment epithelial cells. Exp Eye Res 2008;86: Okunuki Y, Usui Y, Kezuka T, Hattori T, Masuko K, Nakamura H, Yudoh K, Goto H, Usui M, Nishioka K, Kato T, Takeuchi M. Proteomic surveillance of retinal autoantigens in endogenous uveitis: implication of esterase D and brain-type creatine kinase as novel autoantigens. Mol Vis 2008;14: Wakabayashi Y*, Usui Y*, Okunuki Y*, Takeuchi M, Kezuka T, Iwasaki T, Goto H. Increased levels of monokine induced by interferon-gamma (Mig) in the vitreous of patients with diabetic retinopathy. Diabet Med 2008;25: Okunuki Y, Kezuka T, Usui Y, Takeuchi M, Sakai J, Goto H. Review of uveitis associated with psoriasis. Japanese Journal of Clinical Ophthalmology. 2008;62: (Japanese) 13. Okunuki Y, Usui Y, Nagai N, Kezuka T, Ishida S, Takeuchi M, Goto H. Suppression of experimental autoimmune uveitis by angiotensin II type 1 receptor blocker telmisartan. Invest Ophthalmol Vis Sci 2009;50: Hattori T, Kezuka T, Usui Y, Okunuki Y, Takeuchi M, Maruyama K, Haneda M, Shirato S, Goto H. 5

6 Human iris pigment epithelial cells suppress T-cell activation via direct cell contact. Exp Eye Res 2009;89: Takeuchi A, Takeuchi M, Oikawa K, Sonoda KH, Usui Y, Okunuki Y, Takeda A, Oshima Y, Yoshida K, Usui M, Goto H, Kuroda M. Effects of dioxin on vascular endothelial growth factor (VEGF) production in the retina associated with choroidal neovascularization. Invest Ophthalmol Vis Sci 2009;50: Usui Y, Takeuchi M, Hattori T, Okunuki Y, Nagasawa K, Kezuka T, Okumura K, Yagita H, Akiba H, Goto H. Suppression of experimental autoimmune uveoretinitis by regulatory dendritic cells in mice. Arch Ophthalmol 2009;127: Wakabayashi Y*, Usui Y*, Okunuki Y*, Kezuka T, Takeuchi M, Goto H, Iwasaki T. Correlation of vascular endothelial growth factor with chemokines in the vitreous in diabetic retinopathy. Retina 2010;30: Ma J, Usui Y, Takeuchi M, Okunuki Y, Kezuka T, Zhang L, Mizota A, Goto H. Human uveal melanoma cells inhibit the immunostimulatory function of dendritic cells. Exp Eye Res 2010;91: Usui Y, Takeuchi M, Yamakawa N, Takeuchi A, Kezuka T, Ma J, Matsuda R, Okunuki Y, Akiba H, Goto H. Expression and function of inducible costimulator on peripheral blood CD4+ T cells in Behçet's patients with uveitis: a new activity marker? Invest Ophthalmol Vis Sci 2010;51: Takeuchi M, Usui Y, Okunuki Y, Zhang L, Ma J, Yamakawa N, Hattori T, Kezuka T, Sakai JI, Goto H. Immune responses to interphotoreceptor retinoid-binding protein and S-antigen in Behcet's patients with uveitis. Invest Ophthalmol Vis Sci 2010;51: Takeuchi M, Iwasaki T, Kezuka T, Usui Y, Okunuki Y, Sakai JI, Goto H. Functional and morphological changes in the eyes of Behçet's patients with uveitis. Acta Ophthalmol 2010;88: Zhang L, Ma J, Takeuchi M, Usui Y, Hattori T, Okunuki Y, Yamakawa N, Kezuka T, Kuroda M, Goto H. Suppression of experimental autoimmune uveoretinitis by inducing differentiation of regulatory T cells via activation of aryl hydrocarbon receptor. Invest Ophthalmol Vis Sci 2010;51: Usui Y, Kezuka T, Takeuchi M, Okunuki Y, Goto H. Retinal Nerve Fiber Layer Thickness and Optic Nerve Head Morphometry in Acute Retinal Necrosis. Journal of the eye. 2010,27 : (Japanese) 24. Okunuki Y, Usui Y, Kezuka T, Takeuchi M, Goto H. Four cases of bilateral acute retinal necrosis with a long interval after the initial onset. Br J Ophthalmol 2011;95: Okunuki Y, Usui Y, Katai N, Kezuka T, Takeuchi M, Goto H, Wakabayashi Y. Relation of intraocular concentrations of inflammatory factors and improvement of macular edema after vitrectomy in branch retinal vein occlusion. Am J Ophthalmol 2011;151: Wakabayashi Y*, Usui Y*, Okunuki Y*, Ueda S, Kimura K, Muramatsu D, Kezuka T, Goto H. Intraocular VEGF level as a risk factor for postoperative complications after vitrectomy for proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2012;53: Umazume K, Usui Y, Wakabayashi Y, Okunuki Y, Kezuka T, Goto H. Effects of soluble CD14 and 6

7 cytokine levels on diabetic macular edema and visual acuity. Retina. 2013;33: Matsuda R, Kezuka T, Nishiyama C, Usui Y, Matsunaga Y, Okunuki Y, Yamakawa N, Ogawa H, Okumura K, Goto H. Interleukin-10 Gene-transfected Mature Dendritic Cells Suppress Murine Experimental Autoimmune Optic Neuritis. Invest Ophthalmol Vis Sci 2012,53: Usui Y, Wakabayashi Y, Okunuki Y, Kimura K, Tajima K, Matsuda R, Ueda S, Ma J, Nagai T, Mori H, Kezuka T, Nagao T, Goto H. Immune mediators in vitreous fluids from patients with vitreoretinal B cell lymphoma. Invest Ophthalmol Vis Sci 2012,53: Matsuda R, Kezuka T, Nishiyama C, Usui Y, Matsunaga Y, Okunuki Y, Yamakawa N, Ogawa H, Okumura K, Goto H. Suppression of Murine Experimental Autoimmune Optic Neuritis by Mature Dendritic Cells Transfected with Calcitonin Gene-Related Peptide Gene. Invest Ophthalmol Vis Sci 2012;53: Okunuki Y, Usui Y, Nakagawa H, Tajima K, Matsuda R, Ueda S, Hattori T, Kezuka T, Goto H. Peroxisome proliferator-activated receptor-γ agonist pioglitazone suppresses experimental autoimmune uveitis. Exp Eye Res 2013;116: Muramatsu D, Wakabayashi Y, Usui Y, Okunuki Y, Kezuka T, Goto H. Correlation of complement fragment C5a with inflammatory cytokines in the vitreous of patients with proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2013;251: Umazume K, Usui Y, Wakabayashi Y, Okunuki Y, Kezuka T, Goto H. Effects of soluble CD14 and cytokine levels on diabetic macular edema and visual acuity. Retina. 2013;33: Umazume A, Kezuka T, Okunuki Y, Ooshita M, Usui Y, Hirano M, Yamashina A, Goto H. Prediction of severe cardiac involvement by fundus lesion in sarcoidosis. Jpn J Ophthalmol. 2014;58: Agawa T, Usui Y, Wakabayashi Y, Okunuki Y, Juan M, Umazume K, Kezuka T, Takeuchi M, Yamauchi Y, Goto H. Profile of Intraocular Immune Mediators in Patients with Age-Related Macular Degeneration and the Effect of Intravitreal Bevacizumab Injection. Retina. 2014;34: Okunuki Y, Tsubota K, Kezuka T, Goto H. Differences in the clinical features of two types of Vogt- Koyanagi-Harada disease: serous retinal detachment and optic disc swelling. Jpn J Ophthalmol. 2015;59: Matsuda R, Kezuka T, Umazume A, Okunuki Y, Goto H, Tanaka K. Clinical Profile of Anti-Myelin Oligodendrocyte Glycoprotein Antibody Seropositive Cases of Optic Neuritis. Neuroophthalmology. 2015;39: Sweigard JH, Matsumoto H, Smith KE, Kim LA, Paschalis EI, Okunuki Y, Castillejos A, Kataoka K, Hasegawa E, Yanai R, Husain D, Lambris JD, Vavvas D, Miller JW, Connor KM. Inhibition of the alternative complement pathway preserves photoreceptors after retinal injury. Sci Transl Med. 2015;7(297):207ra Usui Y, Tsubota K, Agawa T, Ueda S, Umazume K, Okunuki Y, Kezuka T, Yamakawa N, Goto H. Aqueous immune mediators in malignant uveal melanomas in comparison to benign pigmented intraocular tumors. Graefes Arch Clin Exp Ophthalmol. 2017;255: Hasegawa E, Inafuku S, Mulki L, Okunuki Y, Yanai R, Smith KE, Kim CB, Klokman G, Bielenberg DR, Puli N, Falck JR, Husain D, Miller JW, Edin ML, Zeldin DC, Lee KSS, Hammock BD, Schunck WH, Connor KM. Cytochrome P450 monooxygenase lipid metabolites are significant second 7

8 messengers in the resolution of choroidal neovascularization. Proc Natl Acad Sci U S A. 2017;114(36):E7545-E Mukai R, Okunuki Y, Husain H, Kim CB, Lambris JD, Connor KM. The complement system is critical in maintaining retinal integrity during aging. Front Aging Neurosci. 2018;10: Okunuki Y, Mukai R, Pearsall EA, Klokman G, Husain D, Park DH, Korobkina E, Weiner HL, Butovsky O, Ksander BR, Miller JW, Connor KM. Microglia inhibit photoreceptor cell death and regulate immune cell infiltration in response to retinal detachment. Proc Natl Acad Sci U S A Jul 3;115(27):E6264-E6273. Accepted Manuscripts Manuscripts in Submission Other peer-reviewed scholarship Case reports 1. Morichi Y, Usui Y, Okunuki Y, Sakai J, Goto H. A Case of Acute Retinal Necrosis: Recurrence in Fellow Eye 3 and 21 Years after initial onset. Journal of the eye. 2011; (Japanese) 2. Okunuki Y, Katai N, Yokoi K, Goto H. Sympathetic ophthalmia with poor visual outcome complicates a case of retinal artery circulatory disturbance. Journal of the Eye, 2012;29: (Japanese) 3. Okunuki Y, Sakai J, Kezuka T, Goto H. A case of herpes zoster uveitis with severe hyphema. BMC Ophthalmol. 2014;29: Non-peer reviewed scholarship in print or other media: Reviews, chapters, monographs and editorials Reviews 1. Okunuki Y. Comprehensive analysis of autoantigens in endogenous uveitis by proteomic approach. Journal of Japanese Ocular Inflammation Society 2013;15:14-19 (Japanese) 2. Kezuka T, Matsunaga Y, Matsuda R, An G, Usui Y, OkunukiY, et al. Optic neuritis--immunological approach to elucidate pathogenesis and develop innovative therapy. J Jpn Ophthalmol Soc 2013;7: (Japansese) Summary of selected abstracts at meetings Okunuki Y. Factors associated with chronicity in Vogt-Koyanagi-Harada disease. Selected abstracts. Japanese Journal of Ophthalmology (Japanese) Summary of selected manuscripts Okunuki Y. Relation of intraocular concentrations of inflammatory factors and improvement of macular edema after vitrectomy in branch retinal vein occlusion. Summary of Manuscripts in Foreign Languages. Japanese Journal of Ophthalmology 2011;115 (9) (Japanese) 8

9 Books/textbooks for the medical or scientific community 1. Okunuki Y, Goto H. Vogt-Koyanagi-Harada disease. Ganka. 2012;54: (Japanese) 2. Okunuki Y, Goto H. Vogt-Koyanagi-Harada disease. Ganka. 2012;54: (Japanese) 3. Okunuki Y, Hiroshi G. Acute Retinal Necrosis. Journal of the Eye. 2013;30: (Japanese) 4. Okunuki Y. Vogt-Koyanagi-Harada disease. Rinsho Ganka Expert. 2013: (Japanese) 5. Okunuki Y. Vogt-Koyanagi-Harada disease. Japanese Journal of Clinical Ophthalmology. 2013;67: (Japanese) 6. Okunuki Y. Doença de Vogt-Koynagi-Harada. Retina Clinica Parte 4, Texto e Atlas. 2016, p (Spanish) Thesis: Okunuki Y, Usui Y, Takeuchi M, Kezuka T, Hattori T, Masuko K, Nakamura H, Yudoh K, Usui M, Nishioka K, Kato T. Proteomic surveillance of autoimmunity in Behcet's disease with uveitis: Selenium binding protein is a novel autoantigen in Behcet's disease. Exp Eye Res. 2007,84: Abstracts, Poster Presentations and Exhibits Presented at Professional Meetings: Abstracts 1. The effect of dietary suppression with omega-3 and omega-6 long-chain polyunsaturated fatty acids on retinal detachment. The Association for Research in Vision and Ophthalmology The role of microglial expression of microrna-155 on a murine model of retinal detachment. The Association for Research in Vision and Ophthalmology mir-155 regulates microglia activation in a murine model of retinal detachment. The Association for Research in Vision and Ophthalmology Meeting commendations 1. The 51st annual general assembly and scientific meeting of the Japan College of Rheumatology. Comprehensive analysis of retinal autoantigens in Behcet s disease with uveitis by proteomics. Apr Yokohama, Japan. 2. The 114th annual meeting of the Japanese Ophthalmological society. Analysis in the relation between IL-17 production from peripheral blood mononucler cells and effect of corticosteroid treatment in Vogt-Koyanagi-Harada disease. Apr Nagoya, Japan. Narrative Report 9

10 I am an ophthalmologist with 8 years of clinical experience and 7 years of research experience. I have a strong research background in retinal inflammatory diseases, especially in uveitis based in Japan. After graduating medical school in Japan, I joined department of ophthalmology in Tokyo Medical University in 2003 and started the PhD program. My research goal in graduate school was to identify novel retinal autoantigens in uveitis using a proteomics approach. Through this project, I learned many basic experimental techniques in molecular biology, as well as techniques for ophthalmology research. I found several retinal autoantigens in human patients with uvetis and in an animal model of autoimmune uveitis, which became my thesis. After I received PhD in 2007, I continued my training as a clinical ophthalmologist at Tokyo Medical University, and majored uveitis as a specialty. I engaged in outpatient as well as surgery and inpatient care. In the last two years of my clinical work, I served as a chief of doctors consisting of 4-5 members. During my practice in Japan, I continued research on retinal inflammation and received three research grants from the Japan Society for the Promotion of Science, which is equivalent to NIH in the US. I published 41 scientific papers, 11 of which as first author. My clinical experience with patients inspired me to focus on research in ocular inflammation. In 2014, I joined Dr. Kip M Connor s lab at Massachusetts Eye & Ear, and began several projects surrounding retinal microglia, which are the retina s resident immune cells. Currently, my research focuses on the role for microglia in retinal inflammatory diseases, including uveitis and retinal detachment. I am already a co-author in three scientific papers published from Connor lab, and now have an accepted first-author manuscript that will be published in PNAS. My ultimate career goal is to become a leading clinician scientist by making lasting contributions to elucidating the mechanisms of ocular inflammation. 10

Misdiagnosed Vogt-Koyanagi-Harada (VKH) disease and atypical central serous chorioretinopathy (CSC)

HPTER 12 Misdiagnosed Vogt-Koyanagi-Harada (VKH) disease and atypical central serous chorioretinopathy (S) linical Features VKH disease is a bilateral granulomatous panuveitis often associated with exudative