Mass Eye and Ear Titles

Director, Cornea and Refractive Surgery Service
Associate Chief for Academic Programs
W. Clement Stone Clinical Research Scholar 
Senior Scientist, Laboratory of Corneal Immunology, Transplantation and Regeneration

Harvard Medical School Titles

Director, Harvard-Vision Clinical Scientist Development Program
Co-Director, Cornea Center of Excellence
Member, PhD Program in Immunology

Center/Research Area Affiliations

• Cornea Center of Excellence

Biography

Dr. Reza Dana is an internationally recognized expert in corneal disorders and ocular inflammation. He conducts both basic and translational research in the field of corneal and transplantation immunology. At Schepens Eye Research Institute of Mass. Eye and Ear, he studies the molecular and cellular mechanisms of ocular inflammation with applications to autoimmunity, transplantation, dry eye disease, and angiogenesis.

A Gold Fellow of the Association for Research in Vision and Ophthalmology (ARVO), he has authored more than 480 peer-reviewed articles and over 150 reviews and book chapters, and has presented more than 250 invited and named lectures worldwide. His published work has been cited more than 36,000 times and has an h-index of 94. Dr. Dana's translational research has led to several successful physician-sponsored IND applications to the FDA. His research is supported by several NIH and other federal grants.

Dr. Dana has trained more than 95 clinical fellows, and 140 postdoctoral fellows and students in his laboratory from over 36 countries to date, the significant majority holding full-time academic positions in ophthalmology and vision research. He is recipient of the Harvard Medical School A. Clifford Barger Excellence in Mentoring Award, ARVO’s Cogan (2003) and Fridenwald (2018) awards, the Ellis Island Medal of Honor (2019), as well as ISER’s Endre A. Balazs Prize (2016) and the Stein Innovation Award from Research to Prevent Blindness (2018)

Research Interests

Dr. Dana is an ophthalmologist and immunologist whose principal research interest is in determining the molecular and cellular regulation of corneal and ocular surface immunity. His laboratory focuses on the role of cytokines and chemokines in the induction of antigen-specific corneal immunity, activation of antigen-presenting cells, and the interface of hemangiogenesis and lymphangiogenesis in inflammation. Other areas of active research include the dysfunction of regulatory T cells in autoimmunity,and dry eye disease, and high-risk corneal transplantation. In addition, his group has broadened its focus to include novel animal models for high-risk corneal stem cell transplantation, keratoprosthesis and biosynthetic corneal constructs.

Dr. Dana leads one of the most active translational programs in ophthalmology. As of last count, 50+ prospective investigator-initiated studies were being performed by the Cornea Center faculty. Studies have focused on novel strategies to manage high-risk corneal and stem cell transplants, pathological corneal angiogenesis, dry eye, graft-versus-host disease (GVHD) and in vivo corneal immuno- and neuro-imaging. These studies have been facilitated by 15 successful FDA Investigational New Drug (IND) approvals received since 2008.

Dr. Dana has delivered more than 250 invited and named lectures worldwide, and has received multiple awards, including the Friedenwald Award from the Association for Research in Vision and Ophthalmology (ARVO), the Endre Balazs Prize from International Society for Eye Research, Research to Prevent Blindness (RPB) William and Mary Greve Special Scholar Award, RPB Physician-Scientist Merit Award, RPB Lew Wasserman Merit Award, the RPB Senior Investigator Award, the Achievement Award of the American Academy of Ophthalmology, the Cogan Award of ARVO, the Louisiana State University Chancellor’s Award in Neuroscience and Ophthalmology, and the Alcon Research Institute Award, among many others.

Teaching and Mentoring

A Harvard Medical School Clifford Barger Excellence in Mentoring Award recipient, Dr. Dana has focused extensively on teaching both clinical and basic researchers, which includes postdoctoral research fellows, clinical fellows and residents, medical students, and graduate students enrolled in various Harvard Medical School curricula. He has served as primary mentor to more than 140 laboratory trainees from 36 countries, as well as more than 95 clinical fellows. A strong advocate for clinical scientists in bridging the wide gap between basic science and clinical applications, he directs 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. He has served as PI/Director for this program since its inception at Harvard Ophthalmology in 2004.

Education

BA, Johns Hopkins University (1985)

MPH, Johns Hopkins University (1989)

MD, Johns Hopkins University (1989)

MSc, Health Care Management, Harvard University (2005)

Postgraduate Training

Internship: Greater Baltimore Medical Center (1989-1990)

Residency: Illinois Eye & Ear Infirmary (1990-1993)

Clinical Fellowship in Cornea and External Diseases: Wills Eye Hospital (1993-1994)

Clinical Fellowship in Immunology and Uveitis: Mass Eye and Ear (1994-1995)

Research Fellowship in Ocular and Transplantation Immunology: Schepens Eye Research Institute, Harvard Medical School (1994-1996)

Academic Appointments

1995: Instructor in Ophthalmology, Harvard Medical School

1997: Assistant Professor of Ophthalmology and Assistant Scientist, Schepens Eye Research Institute of Mass Eye and Ear

2000: Associate Professor of Ophthalmology, Harvard Medical School and  Associate Scientist, Schepens Eye Research Institute of Mass Eye and Ear

2002-present: W. Clement Stone Scholar

2004-present: Senior Scientist, Schepens Eye Research Institute of Mass Eye and Ear

2006-present: Director of the Cornea and Refractive Surgery Service of Mass Eye and Ear

2007-present: Claes Dohlman Chair in Ophthalmology, Harvard Medical School

2008-present: Vice Chair for Academic Programs, Ophthalmology, Harvard Medical School and Associate Chief for Academic Programs, Mass Eye and Ear

Honors

2021: Susruta Lecture, University of Pittsburgh

2021: Bowman Club-David Easty Lecture, UK

2021: Snell Memorial Lecture, University of Rochester

2020: The Ophthalmologist ‘Power List’ 2020

2019: Champalimaud Lecture, LV Prasad Eye Institute

2019: Ellis Island Medal of Honor, New York NY

2018: C. Stephen and Frances Foster Lectureship, Duke University

2018: Honorary Keynote Lecture, 120th Korean Ophthalmological Society

2018: Stein Innovation Award, Research to Prevent Blindness

2018: Friedenwald Award, Association for Research in Vision and Ophthalmology (ARVO)

2017: Streilein Lecture, 30th Biennial Cornea Conference

2017: Senior Achievement Award, American Academy of Ophthalmology

2017: Plenary Address, 121st Meeting of the Japanese Ophthalmological Society

2016: Endre A. Balazs Prize, International Society for Eye Research

2016: Mooney Lecture, Irish College of Ophthalmologists, Rep. Ireland

2016: Elected, Academia Ophthalmologica Internationalis

2016: Roger Meyer Lecture, University of Michigan Kellogg Eye Center

2015: Keynote Address and Certificate of Honor, European Association for Vision and Eye Research

2015: Kersley Lecture, British Ocular Surface Society, London, England

2014: Thygeson Lecture, Ocular Microbiology and Immunology Group

2014: A. Clifford Barger Excellence in Mentoring Award, Harvard Medical School

2013: Keynote Speaker, European Society of Ophthalmology (SOE), Copenhagen, Denmark

2013: Gold Fellow, ARVO

2013: Senior Scientific Investigator Award, Research to Prevent Blindness

2012: Mentoring Award, European Young Investigator Network for Ocular Surface Inflammation

2012: LSU Chancellor’s Award in Neuroscience and Ophthalmology

2011: Joaquin Barraquer Lecture, Spanish Congress of Ophthalmology

2011: David Easty Lecturer, Bowman Club, Royal College of Surgeons, Edinburgh

2009: Research to Prevent Blindness Lew R. Wasserman-Merit Award

2008: Alcon Research Institute Award

2006: Service Recognition Award, American Academy of Ophthalmology

2005: Research to Prevent Blindness Physician Scientist-Merit Award

2004: Keynote Address, 28th All-Japan Cornea Conference, Yonago, Japan

2004: Alta Lecturer and visiting professorship, Univ. California San Francisco

2003: Dohlman Lecturer, Boston Biennial Cornea Conference

2003: Cogan Award, Association for Research In Vision and Ophthalmology

2002: Fry Memorial Lecturer, Wills Eye Hospital Biennial Cornea Conference

2002: Kronfeld Memorial Lecturer, Illinois Eye & Ear Infirmary

2002: Achievement Award, American Academy of Ophthalmology

1999: Research to Prevent Blindness William & Mary Greve Special Scholar

1996: Clinical Scientist Career Award (K08), National Institutes of Health

Identification of Novel APC Populations

Our studies let to several 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 myeloid CD11c+ dendritic cells) in the central cornea (IOVS 2002, J Leuk Bio 2003), breaking a longstanding dogma that the cornea was devoid of functional antigen-presenting cells. We also showed that these immature/precursor myeloid populations can mature to acquire high levels of costimulatory molecules CD40 and CD80, as well as MHC class II expression as they egress the eye through selective upregulation of specific receptors to prime naïve T cells under conditions of inflammation. This discovery had practical implications, as it demonstrated how the cornea itself (including corneal transplants) can contribute to immunity through resident APC, a process known as ‘direct sensitization,’ particularly in states of high tissue inflammation (J Immunology 2004).

APC-Lymphatic Interactions

To determine precisely where and how corneal APC interact with T cells, we embarked on a series of investigations that established the local draining lymph nodes as the site of allosensitization (IOVS 2001; J Exp Med 2002). Remarkably, before these studies, the field was almost exclusively focused on APC-T cell interactions in the spleen. Subsequent studies showed that APC localization in these draining lymphoid tissues is reliant on a novel function of the VEGFR-3 receptor, known to be a growth factor for lymphatic and budding blood vessel endothelia. We determined that this receptor is acquired by mature MHC class IIhi dendritic cells in the cornea, and mediates their chemotactic mobilization into lymphatics, thereby allowing their egress from the inflamed eye. We also showed that blockade of this pathway can suppress the trafficking of APC from the eye to regional lymph nodes and suppress the induction of immunity to ocular antigens (Nature Medicine 2004). The identification of this novel role for VEGFR-3 in APC mobilization received considerable attention since subsquent work by others showed a similar mechanism to be operative for certain epithelial cancers and peritumor cells for gaining access to the lymphatic system for systemic spread.

Regulation of Corneal Angiogenesis and Lymphangiogenesis

Our studies on VEGFR-3 function stumbled us onto entirely unexpected insights into how corneal avascularity is maintained. We found high constitutive ‘ectopic’ expression of non-signaling VEGFR-3 by the corneal epithelium, and described how this “sink” mechanism for binding VEGF-C/D prevents their ligation of their receptors VEGFR-2/3, thereby functioning as a critical mechanism for maintaining corneal avascularity and regulating immunity (PNAS 2006). More recently, we have shown that this regulatory function can be subverted by IL-17 binding to epithelial cells, which have functional IL-17R signaling, inducing over-expression of VEGF-D by epithelial cells (Blood 2011).

Failure of Immunoregulatory Mechanisms in Inflammation

We have determined that Foxp3+ regulatory T cells (Tregs) become dysfunctional in hosts prone to reject allografts as well as in chronic ocular surface disease (J Immunology 2009). Our work has uncovered mechanisms that regulate Treg plasticity and regulatory breakdown in highly inflamed microenvironments, identifying different Treg phenotypes (Sci Reports 2016). We have identified Treg plasticity as a key factor in loss of allotolerance, and have defined novel strategies to (i) enhance Treg homing to the immune synapse (J Immunology 2014) and (ii) promote Treg expansion (Transplantation 2016) for induction of graft tolerance.

Dry Eye Disease (DED) Immunopathogenesis

Our work in corneal transplantation immunology permitted us since the mid-2000s to launch a program determining the immunopathogenesis of dry eye disease (DED), a chronic immune-mediated disease (and one of the most common reasons for patients seeking eye care) whose precise pathogenesis was barely understood even a few years earlier. We optimized a murine model for dry eye disease that did not rely on gene deletion or transgenic technology and used it in our basic research program to identify critical features in the immunopathogenesis of DED. Our work led to several novel discoveries, including identifying a select resistance of T helper-17 (Th17) cells, the principal pathogenic effectors in DED, to suppression by regulatory T cells (J Immunology 2009).

We subsequently showed that failure in Treg function in chronic DED leads not only to expansion of Th17 effectors but also development of classic immunologic memory mediated by effector memory IL-17 secreting cells (Mucosal Immunology 2014). Very recently, we have focused on the molecular mechanisms that lead to generation and maintenance of memory Th17 cells- an almost entirely unexplored area—and showed the critical function of IL-7 and IL-15 in this process (J Autoimmunity 2017).

Translational Research

In addition to these basic investigations, I am engaged in translational research. These projects have focused on novel immunomodulatory strategies to manage high-risk corneal and stem cell transplants, pathological corneal angiogenesis, graft-versus-host disease, dry eye, and in vivo corneal immuno- and neuro-imaging. Our group has been one of the first to develop and clinically test topical protein-based biologic approaches targeting specific inflammatory and pro-angiogenic cytokines (such as VEGF, IL-1, PDGF) in the management of corneal and ocular surface diseases in patients. These studies have been facilitated by 9 successful FDA Investigational New Drug (IND) submissions from my group since 2008.

New Areas of Investigation

While we have maintained our focus on immunology and immune regulation, our group has gradually broadened its focus to include novel animal models for high-risk corneal and stem cell transplantation, keratoprosthesis and biosynthetic corneal constructs. Our group was the first to develop a miniature keratoprosthesis for the mouse and stereotactic brain surgery models for corneal.

Executive Assistant

Linda Benson

Scientific Research Manager

Mojgan Pishyaren MT, MS

Laboratory manager

Qiang Zhang,MD

Postdoctoral Research Fellows

Hamid Alemi, MD, MPH
Tomas Blanco, PhD
Jimena Tatiana Carreno Galeano, MD
Francesca Kahale, MD
Seokjoo Lee, PhD
Catherine Liu, MD
Ayten Musayeva, MD
Gustavo Ortiz, PhD
Rohan Singh, MD
Shudan Wang, MD
Shuyan Zhu, MD

Pre-doctoral Research Fellows

Ann Yung, MA
Amirreza Naderi