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Reza Dana, M.D.

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Biography
1995
Fellowship (Ocular Immunology)
1996
Named Fellow of the Society of Heed Fellows (Special Recognition Award)
1996
Clinical Scientist Career Award
1999
Invited Participant
1999
William and Mary Greve Scholar (RPB Special Scholar Award)
2000
Second Decade Society (alumni honor)
2002
Achievment Award
2002
Kronfeld Memorial Lecturer
2002
Fry Memorial Lecturer
2003
Cogan Award
2003
Dohlman Lecturer
2004
Alta Lecturer and Visiting Professorship
2004
Keynote Speaker
2005
Physician Scientist Merit Award
2006
Service Recognition Award
2007
Certificate of Appreciation
2008
Alcon Research Institute Award
2009 - 2010
Lew R. Wasserman Merit Award
2011
David Easty Lecturer
2011
Joaquin Barraquer Lecturer
2012
Chancellor’s Award in Neuroscience and Ophthalmology
2012
Mentoring Award
2013
Gold Fellow
2013
Keynote Speaker
2013
Senior Scientific Investigator Award
2014
A. Clifford Barger Excellence in Mentoring Award
2014
Thygeson Lecturer

Overview
I am an ophthalmologist and immunologist whose principal research interest is determining the molecular and cellular regulation of corneal and ocular surface immunity. In particular, we focus on the role of cytokines and chemokines in induction of antigen-specific corneal immunology, recruitment and activation of ocular antigen-presenting cells, and the interface of lymphangiogenesis and corneal inflammation. The principal venue of my research activities is in my laboratory at the Schepens Eye Research Institute, but is complemented with extensive ‘clinic-to-lab’ and translational ‘lab-to-clinic’ research activities that are performed in conjunction with my academic clinical subspecialty practice at the Massachusetts Eye and Ear Infirmary (see further below for details).

To address the principal objectives of our research program, we optimized the orthotopic model of corneal transplantation in the mouse to determine specific mechanisms involved in: (i) antigen-presenting cell (APC) mobilization in the cornea, (ii) APC-blood and –lymph vessel interactions, (iii) APC mobilization from eye to lymphoid organs including regional draining lymph nodes, and (iv) APC sensitization of T cells in transplantation and autoimmunity. Our work has been instrumental in delineating the precise mechanisms by which pro-inflammatory cytokines work in concert to upregulate specific chemokines and cell adhesion molecules that mediate trans-endothelial migration of APCs from the intravascular compartment into the corneo-limbal matrix. We have shown that this process of APC mobilization into the corneal matrix can be effectively suppressed, with concomitant blunting in the activation of cornea-specific immunity, with topical blockade of relevant cytokines and chemokines. We subsequently showed that once mobilized, these antigen-laden APCs can migrate from the graft to regional lymph nodes to induce T helper-1 type immunity through an interleukin-12-dependent mechanism. This pathway which becomes activated in states of high inflammation is distinct from the normal (default) migration of “tolerogenic” ocular APC to the spleen where they can promote a specific form of immune unresponsiveness termed anterior chamber-associated immune deviation, explaining how the eye, an immune privileged organ, can also be susceptible to destructive immunity. We have also shown the T cell response generated differs considerably between transplants and in chronic autoimmunity (the latter as seen in dry eye disease).

Our work led to important novel and unexpected discoveries. My lab was the first to discover several distinct populations of uniformly MHC class II— highly immature APCs (including epithelial Langerhans cells and stromal CD11b+ myeloid CD11c+ dendritic cells) in the central cornea, breaking a longstanding dogma that the cornea was devoid of any antigen-presenting cell population. We also showed that these immature/precursor populations can mature to acquire high CD40, CD80, and MHC class II expression as they egress the eye through selective upregulation of specific receptors (e.g. CCR7) to prime naïve T cells under conditions of inflammation, including after corneal transplantation. We have also determined a novel role for the tyrosine kinase receptor vascular endothelial growth factor receptor-3 (VEGFR-3), which is known to be a growth factor for lymphatic (and to some extent budding blood vessel) endothelia. We have determined that this receptor is expressed by mature MHC class IIhi dendritic cells in the cornea, and mediates their chemotactic mobilization into lymphatics, thereby allowing their egress from the eye. Importantly, we showed that blockade of this pathway can suppress the trafficking of APC from the eye to regional lymph nodes and suppress the induction of delayed hypersensitivity to corneal transplants—a finding we published in Nature Medicine. We have also successfully demonstrated that disruption of the ‘eye-lymphatic axis’ pharmacologically can suppress generation of autoimmune dry eye disease.

Our work has also shed light onto one of the oldest mysteries in ophthalmic biology—namely, how the cornea maintains its avascular structure, and thereby allows for light to be focused on the retina with minimal interference. We have shown high constitutive and ectopic expression of VEGFR-3 by the corneal epithelium serves as a “sink” mechanism for VEGF-C/D, preventing their ligation of vascular endothelial VEGFR-2, and thereby functioning as a critical mechanism for maintaining corneal avascularity (PNAS). More recently, we have shown that IL-17 can promote lymphatic development through upregulation of VGEF-D (Blood).

Our work in corneal transplantation immunology permitted us since 2006 to launch a broad and productive program determining the immunopathogenesis of dry eye disease, a chronic autoimmune disease whose precise pathogenesis was barely understood even a few years earlier. We developed, and validated, a novel preclinical model for dry eye disease that did not rely on gene deletion or transgenic technology and used it in our basic research program to focus on the molecular mechanisms that mediate (i) selective growth of neolymphatics into dry eye corneas, (ii) induction of T helper-1 (Th1) and Th17 autoimmunity, (iii) development of Th17 cell resistance to Treg suppression, and (iv) the expression of autoreactive T cell homing chemokines on the ocular surface. These studies have been complemented with a number of ‘proof of concept’ therapeutic strategies in preclinical models of dry eye, such as antagonism of cytokines (IL-1, IL-17), prolymphangiogenic factors (VEGF-C/D, VEGFR-3), T cell homing chemokines (CCR5), and leukocyte recruitment mechanisms such as integrins (VLA-4). More recently, we have shown that development of chronic ocular surface/dry eye disease is linked to development of effector memory IL-17 secreting cells, whose function amplifies autoimmunity by suppressing regulatory T cells pathways.

These basic investigation efforts have been complemented with an active program in clinical and translational research. We created the Cornea Research department at the Mass Eye and Ear in 2007 and the Ocular Surface Imaging Center in 2009; these are staffed by several full-time staff, where a large number of investigator-initiated studies are performed. Studies have focused on novel strategies to manage high-risk corneal and stem cell transplants, pathological corneal angiogenesis, dry eye, and in vivo corneal immuno- and neuro-imaging. Our group has been one of the first to develop and clinically test biologic approaches in the management of corneal and ocular surface diseases. These studies have been facilitated by 8 successful FDA IND approvals received by our group since 2008. In all, the combined research efforts of the Dana group have led to over 200 peer-reviewed publications.

In addition to research, I have focused extensively on education, both clinical and research. This has included teaching of postdoctoral research fellows, clinical fellows and residents, and medical students and graduate students enrolled in various Harvard Medical School curricula—I have served as primary mentor to over 80 trainees from 29 countries. In addition to my considerable efforts to contribute to the investigation-based peer-reviewed literature, I served as one of the editors to the 14-volume American Academy of Ophthalmology Basic and Clinical Science Course (the principal educational tool of US and Canadian residents for Board certification), responsible for content in corneal inflammation and immunity. Finally, as a strong believer in the importance of clinical scientists in bridging the wide gap between basic science and clinical applications, I direct the Harvard-Vision Clinical Scientist Development Program funded by the NIH K12 mechanism- with the express intent of recruiting, training, and retaining the brightest young minds to Harvard to contribute to our research efforts. I have served as PI/Director for this program since its inception at Harvard Ophthalmology in 2004, and successfully received refunding in 2010 to continue the program. The $7M+ we have received for this program since 2004 has led to recruitment of numerous clinician-scientists to the Harvard Department of Ophthalmology.

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R21EY029387 (DANA, REZA) Sep 1, 2018 - Aug 31, 2020
    NIH/NEI
    Efficacy of the Neuropeptide Alpha-Melanocyte Stimulating Hormone (?-MSH) in Promoting Survival of Corneal Endothelial Cells in Eye Banking and Transplantation
    Role: Principal Investigator
  2. R01EY020889 (DANA, REZA) Sep 30, 2010 - Aug 31, 2019
    NIH/NEI
    Immunopathogenic mechanisms of dry eye disease
    Role: Principal Investigator
  3. K24EY019098 (DANA, REZA) Sep 15, 2008 - Aug 31, 2013
    NIH/NEI
    New Strategies for Modulation of Corneal and Ocular Surface Inflammation
    Role: Principal Investigator
  4. R21EY015738 (DANA, REZA) Apr 1, 2005 - Mar 31, 2007
    NIH/NEI
    Promoting Corneal Graft by Anti-Apoptotic Genes
    Role: Principal Investigator
  5. K12EY016335 (DANA, REZA) Sep 30, 2004 - Mar 31, 2021
    NIH/NEI
    Harvard-Vision Clinical Scientist Development Program
    Role: Principal Investigator

Bibliographic
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. Deng SX, Borderie V, Chan CC, Dana R, Figueiredo FC, Gomes JAP, Pellegrini G, Shimmura S, Kruse FE. Global Consensus on Definition, Classification, Diagnosis, and Staging of Limbal Stem Cell Deficiency. Cornea. 2019 Mar; 38(3):364-375. PMID: 30614902.
    Citations:    Fields:    
  2. Dana R, Bradley JL, Guerin A, Pivneva I, Stillman IÖ, Evans AM, Schaumberg DA. Estimated Prevalence and Incidence of Dry Eye Disease Based on Coding Analysis of a Large, All-age United States Health Care System. Am J Ophthalmol. 2019 Feb 02. PMID: 30721689.
    Citations:    
  3. Trujillo-de Santiago G, Sharifi R, Yue K, Sani ES, Kashaf SS, Alvarez MM, Leijten J, Khademhosseini A, Dana R, Annabi N. Ocular adhesives: Design, chemistry, crosslinking mechanisms, and applications. Biomaterials. 2019 Mar; 197:345-367. PMID: 30690421.
    Citations:    Fields:    
  4. Shao C, Chen Y, Nakao T, Amouzegar A, Yin J, Tahvildari M, Lužnik Z, Chauhan SK, Dana R. Local Delivery of Regulatory T Cells Promotes Corneal Allograft Survival. Transplantation. 2019 Jan; 103(1):182-190. PMID: 30247445.
    Citations:    Fields:    
  5. Paschalis EI, Lei F, Zhou C, Chen XN, Kapoulea V, Hui PC, Dana R, Chodosh J, Vavvas DG, Dohlman CH. Microglia Regulate Neuroglia Remodeling in Various Ocular and Retinal Injuries. J Immunol. 2019 Jan 15; 202(2):539-549. PMID: 30541880.
    Citations:    Fields:    
  6. Inomata T, Nakamura M, Iwagami M, Shiang T, Yoshimura Y, Fujimoto K, Okumura Y, Eguchi A, Iwata N, Miura M, Hori S, Hiratsuka Y, Uchino M, Tsubota K, Dana R, Murakami A. Risk Factors for Severe Dry Eye Disease: Crowdsourced Research Using DryEyeRhythm. Ophthalmology. 2018 Dec 11. PMID: 30550734.
    Citations:    Fields:    
  7. Paschalis EI, Lei F, Zhou C, Kapoulea V, Dana R, Chodosh J, Vavvas DG, Dohlman CH. Permanent neuroglial remodeling of the retina following infiltration of CSF1R inhibition-resistant peripheral monocytes. Proc Natl Acad Sci U S A. 2018 11 27; 115(48):E11359-E11368. PMID: 30442669.
    Citations:    Fields:    
  8. Dana R, Bradley JL, Guerin A, Pivneva I, Evans AM, Stillman IÖ. Comorbidities and Prescribed Medications in Patients With or Without Dry Eye Disease: A Population-Based Study. Am J Ophthalmol. 2019 Feb; 198:181-192. PMID: 30312577.
    Citations:    Fields:    
  9. Satitpitakul V, Sun Z, Suri K, Amouzegar A, Katikireddy KR, Jurkunas UV, Kheirkhah A, Dana R. Vasoactive Intestinal Peptide Promotes Corneal Allograft Survival. Am J Pathol. 2018 Sep; 188(9):2016-2024. PMID: 30097165.
    Citations:    Fields:    
  10. Tan X, Chen Y, Foulsham W, Amouzegar A, Inomata T, Liu Y, Chauhan SK, Dana R. The immunoregulatory role of corneal epithelium-derived thrombospondin-1 in dry eye disease. Ocul Surf. 2018 Oct; 16(4):470-477. PMID: 30055331.
    Citations:    
  11. Kheirkhah A, Satitpitakul V, Syed ZA, Müller R, Goyal S, Tu EY, Dana R. Factors Influencing the Diagnostic Accuracy of Laser-Scanning In Vivo Confocal Microscopy for Acanthamoeba Keratitis. Cornea. 2018 Jul; 37(7):818-823. PMID: 29303889.
    Citations:    Fields:    Translation:Humans
  12. Amparo F, Shikari H, Saboo U, Dana R. Corneal fluorescein staining and ocular symptoms but not Schirmer test are useful as indicators of response to treatment in chronic ocular GVHD. Ocul Surf. 2018 Jul; 16(3):377-381. PMID: 29763694.
    Citations:    Fields:    
  13. Hua J, Inomata T, Chen Y, Foulsham W, Stevenson W, Shiang T, Bluestone JA, Dana R. Pathological conversion of regulatory T cells is associated with loss of allotolerance. Sci Rep. 2018 May 04; 8(1):7059. PMID: 29728574.
    Citations:    Fields:    
  14. Sullivan DA, Dana R, Sullivan RM, Krenzer KL, Sahin A, Arica B, Liu Y, Kam WR, Papas AS, Cermak JM. Meibomian Gland Dysfunction in Primary and Secondary Sjögren Syndrome. Ophthalmic Res. 2018; 59(4):193-205. PMID: 29627826.
    Citations:    Fields:    Translation:Humans
  15. Paschalis EI, Lei F, Zhou C, Kapoulea V, Thanos A, Dana R, Vavvas DG, Chodosh J, Dohlman CH. The Role of Microglia and Peripheral Monocytes in Retinal Damage after Corneal Chemical Injury. Am J Pathol. 2018 Jul; 188(7):1580-1596. PMID: 29630857.
    Citations:    Fields:    
  16. Yin J, Kheirkhah A, Dohlman T, Saboo U, Dana R. Reduced Efficacy of Low-dose Topical Steroids in Dry Eye Disease Associated With Graft-versus-Host Disease. Am J Ophthalmol. 2018 Jun; 190:17-23. PMID: 29572107.
    Citations:    Fields:    
  17. Dana R. A New Frontier in Curing Corneal Blindness. N Engl J Med. 2018 03 15; 378(11):1057-1058. PMID: 29539278.
    Citations:    Fields:    
  18. Kheirkhah A, Coco G, Satitpitakul V, Dana R. Subtarsal Fibrosis Is Associated With Ocular Surface Epitheliopathy in Graft-Versus-Host Disease. Am J Ophthalmol. 2018 May; 189:102-110. PMID: 29505774.
    Citations:    Fields:    
  19. Amparo F, Dana R. Web-based longitudinal remote assessment of dry eye symptoms. Ocul Surf. 2018 Apr; 16(2):249-253. PMID: 29409963.
    Citations:    Fields:    
  20. Dohlman CH, Cade F, Regatieri CV, Zhou C, Lei F, Crnej A, Harissi-Dagher M, Robert MC, Papaliodis GN, Chen D, Aquavella JV, Akpek EK, Aldave AJ, Sippel KC, D'Amico DJ, Dohlman JG, Fagerholm P, Wang L, Shen LQ, González-Andrades M, Chodosh J, Kenyon KR, Foster CS, Pineda R, Melki S, Colby KA, Ciolino JB, Vavvas DG, Kinoshita S, Dana R, Paschalis EI. Chemical Burns of the Eye: The Role of Retinal Injury and New Therapeutic Possibilities. Cornea. 2018 Feb; 37(2):248-251. PMID: 29135604.
    Citations: 1     Fields:    Translation:Humans
  21. Eslani M, Putra I, Shen X, Hamouie J, Tadepalli A, Anwar KN, Kink JA, Ghassemi S, Agnihotri G, Reshetylo S, Mashaghi A, Dana R, Hematti P, Djalilian AR. Cornea-Derived Mesenchymal Stromal Cells Therapeutically Modulate Macrophage Immunophenotype and Angiogenic Function. Stem Cells. 2018 May; 36(5):775-784. PMID: 29341332.
    Citations: 1     Fields:    
  22. Tahvildari M, Amouzegar A, Foulsham W, Dana R. Therapeutic approaches for induction of tolerance and immune quiescence in corneal allotransplantation. Cell Mol Life Sci. 2018 05; 75(9):1509-1520. PMID: 29307015.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  23. Inomata T, Hua J, Nakao T, Shiang T, Chiang H, Amouzegar A, Dana R. Corneal Tissue From Dry Eye Donors Leads to Enhanced Graft Rejection. Cornea. 2018 Jan; 37(1):95-101. PMID: 29023237.
    Citations: 1     Fields:    Translation:HumansAnimalsCells
  24. Foulsham W, Coco G, Amouzegar A, Chauhan SK, Dana R. When Clarity Is Crucial: Regulating Ocular Surface Immunity. Trends Immunol. 2018 04; 39(4):288-301. PMID: 29248310.
    Citations:    Fields:    Translation:HumansAnimals
  25. Marmalidou A, Kheirkhah A, Dana R. Conjunctivochalasis: a systematic review. Surv Ophthalmol. 2018 Jul - Aug; 63(4):554-564. PMID: 29128574.
    Citations:    Fields:    Translation:Humans
  26. Inomata T, Mashaghi A, Hong J, Nakao T, Dana R. Scaling and maintenance of corneal thickness during aging. PLoS One. 2017; 12(10):e0185694. PMID: 28985226.
    Citations:    Fields:    Translation:Animals
  27. Eslani M, Putra I, Shen X, Hamouie J, Afsharkhamseh N, Besharat S, Rosenblatt MI, Dana R, Hematti P, Djalilian AR. Corneal Mesenchymal Stromal Cells Are Directly Antiangiogenic via PEDF and sFLT-1. Invest Ophthalmol Vis Sci. 2017 10 01; 58(12):5507-5517. PMID: 29075761.
    Citations: 2     Fields:    Translation:HumansAnimalsCells
  28. Hos D, Bukowiecki A, Horstmann J, Bock F, Bucher F, Heindl LM, Siebelmann S, Steven P, Dana R, Eming SA, Cursiefen C. Transient Ingrowth of Lymphatic Vessels into the Physiologically Avascular Cornea Regulates Corneal Edema and Transparency. Sci Rep. 2017 08 03; 7(1):7227. PMID: 28775329.
    Citations: 1     Fields:    
  29. Kheirkhah A, Kempen J, Dana R. Reply. Am J Ophthalmol. 2017 Oct; 182:202-203. PMID: 28778570.
    Citations:    Fields:    
  30. Kheirkhah A, Crnej A, Ren A, Mullins A, Satitpitakul V, Hamrah P, Schaumberg D, Dana R. Patients' Perceived Treatment Effectiveness in Dry Eye Disease. Cornea. 2017 Aug; 36(8):893-897. PMID: 28481835.
    Citations:    Fields:    Translation:Humans
  31. Jones L, Downie LE, Korb D, Benitez-Del-Castillo JM, Dana R, Deng SX, Dong PN, Geerling G, Hida RY, Liu Y, Seo KY, Tauber J, Wakamatsu TH, Xu J, Wolffsohn JS, Craig JP. TFOS DEWS II Management and Therapy Report. Ocul Surf. 2017 07; 15(3):575-628. PMID: 28736343.
    Citations: 16     Fields:    Translation:Humans
  32. Amparo F, Yin J, Di Zazzo A, Abud T, Jurkunas UV, Hamrah P, Dana R. Evaluating Changes in Ocular Redness Using a Novel Automated Method. Transl Vis Sci Technol. 2017 Jul; 6(4):13. PMID: 28736686.
    Citations:    
  33. Kheirkhah A, Di Zazzo A, Satitpitakul V, Fernandez M, Magilavy D, Dana R. A Pilot Randomized Trial on Safety and Efficacy of a Novel Topical Combined Inhibitor of Janus Kinase 1/3 and Spleen Tyrosine Kinase for GVHD-Associated Ocular Surface Disease. Cornea. 2017 Jul; 36(7):799-804. PMID: 28445193.
    Citations: 2     Fields:    Translation:HumansCTClinical Trials
  34. Lee HS, Amouzegar A, Dana R. Kinetics of Corneal Antigen Presenting Cells in Experimental Dry Eye Disease. BMJ Open Ophthalmol. 2017; 1(1):e000078. PMID: 29354712.
    Citations: