Leo A. Kim, M.D., Ph.D.

Harvard Medical School

Assistant Professor of Ophthalmology

Massachusetts Eye and Ear

Investigator 

Research Summary

Center/Research Area Affiliations

Biography

Dr. Kim is a practicing vitreoretinal surgeon. He has extensive clinical experience in the management of retinal diseases associated with pathologic angiogenesis and is devoted to understanding the mechanisms of vitreoretinal disease. A former NIH-sponsored K12 scholar, Dr. Kim is evaluating neovascular membranes obtained from patients with proliferative diabetic retinopathy in order to understand the underlying mechanisms of aberrant retinal angiogenesis. He is also studying the cell biology of proliferative vitreretinopathy (PVR) membranes obtained from patients. Other areas of interest include retinal toxicities and their mechanisms of cell death, as well as computational modeling of oxygen distribution in dry age-related macular degeneration (AMD) to predict conversion to wet AMD.

Download his CV or biosketch [PDF] for more information.

Education

M.D., Ph.D., Yale University School of Medicine, Medical Scientist Training Program (2005)

Postgraduate Training

Ophthalmology Residency, University of Southern California, Doheny Eye Institute (2009)
Vitreoretinal Fellowship, University of Southern California, Doheny Eye Institute (2011)

Honors

2010: Heed Ophthalmic Foundation Fellow
2008: Heed Ophthalmic Foundation Residents Retreat
2008: Lillian and Henry Nesburn Award for Research Excellence
2008, 2007: Doheny Resident Travel Grant
2007: ARVO Travel Grant Award
2005: Selma and Karl Folkers Prize for Biomedical Research

His Story

Dr. Kim is a clinician scientist and educator. As a clinician, he has broad experience in the management of retinal diseases, specifically: proliferative diabetic retinopathy, proliferative vitreoretinopathy, retinal toxicities, age-related macular degeneration, as well as other retinal vascular diseases that cause pathological angiogenesis.

A former member of the Harvard-Vision Clinical Scientist Development Program, Dr. Kim’s research focuses on the basic understanding of the mechanisms of vitreoretinal disease. Specifically, his research is focused on the cell-death mechanisms of the retina when exposed to commonly used drugs such as tamoxifen and chloroquine. He has discovered and published on the presence of multiple cell death pathways mediated by tamoxifen toxicity, and this work has highlighted possible methods to protect cells against regulated cell death. He has also published extensively on diabetic retinopathy, specifically looking at proliferative diabetic retinopathy (PDR), which is characterized by the formation of abnormal blood vessels within the eye. He has both identified potential genetic factors leading the formation of these blood vessels, and recently identified the role of the transcription factor Runx1 in the formation of aberrant blood vessels within the eye. Finally, he works on a condition called proliferative vitreoretinopathy which is one of the primary causes of recurrent retinal detachment, especially after eye trauma.

Additional Research Interests

  • Mechanisms of age-related macular degeneration and the effect of drusen on retinal oxygenation
  • Evaluating patients and surgical specimens with severe proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR)
  • Genetics of severe PDR and the use of next generation sequencing
  • Role of lymphangiogenesis and angiogenesis in orbital tissue

Projects

Research Interests

  • Proliferative diabetic retinopathy
  • Retinal toxicities
  • Computational modeling of oxygen distribution in dry AMD

Runx1 as a Mediator of Aberrant Retinal Angiogenesis

Dr. Kim and colleagues recently identified the transcription factor Runx1 as a mediator of pathologic retinal angiogenesis in endothelial cells derived from patients with proliferative diabetic retinopathy. They discovered that Runx1 affects endothelial cell proliferation, migration, and tube formation. Inhibition of Runx1 was found to inhibit aberrant angiogenesis in the mouse model of oxygen-induced retinopathy. Future work will investigate the cell signaling mechanisms that mediate Runx1 activity.

Development of an in vitro Model of Proliferative Vitreoretinopathy

Dr. Kim and colleagues recently developed an in vitro model of proliferative vitreoretinopathy using patient-derived membranes. Using this model, they showed that methotrexate can affect cell proliferation and induce cell death. Ultimately, they hope to identify potential drugs that can regulate PVR, as well as explain the underlying cell biology of PVR membranes.

Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease

Dr. Kim and colleagues recently showed that the both angiogenesis and lymphangiogenesis are active in patients with acute thyroid eye disease (TED) compared to patients with chronic TED. This suggests that there is active VEGF signaling in teh acute phase of the disease. Further work is being pursued to produce an animal model of orbital inflammation, which may be used to further understand the interplay between orbital inflammation and VEGF signaling.

Retinal Toxicities

We previously showed that multiple concurrent cell death mechanisms are involved in tamoxifen toxicity of the retinal pigment epithelium. We are currently attempting to understand the cell death mechanisms of chloroquine toxicity of the retina.

Patient-Specific Modeling of Oxygen Distribution for Predicting Retinal Degeneration

The primary objective of this research program is to understand the pathophysiology of age-related macular degeneration (AMD) and to understand how drusen affect outer retinal oxygenation. Currently, no methods exist to non-invasively measure oxygenation of the outer retina of patients. Dr. Kim and colleagues propose are testing the hypothesis that drusen-induced hypoxia of photoreceptors may be a significant factor contributing to the progression of AMD, and that the topography of drusen can be used to predict conversion from dry to wet AMD.

Current Research Funding

2016-2018
NIH/NEI R21 EY027061: Principal Investigator (PI)
Vasculogenesis in thyroid eye disease
$541,750
Thyroid eye disease is a potentially sight-threatening condition, in which about 10-20 percent of patients develop severe inflammation in the eye sockets (orbits) that can lead to disabling double vision or irreversible vision loss. This project investigates the mechanisms responsible for the formation of new blood and lymphatic vessels within the human orbit and investigates whether the regulation of new blood and lymphatic vessel formation can reduce the orbital swelling in a mouse model of acute orbital inflammation.
2016-2019 U.S. Department of Defense: Co-PI
Testing the preclinical efficacy of therapies for proliferative retinopathy
$1,499,592
 Using Dr. Kim's in vitro model of proliferative vitreoretinopathy (PVR), which is termed C-PVR, he aims determine the therapeutic efficacy of multiple FDA-approved drugs. This model recapitulates many of the features found in patients with PVR: cellular proliferation, migration, band formation, and membrane formation. Additional, an in vivo model using these cells will be used to develop animal models that most closely resemble the cellular milieu of PVR.
2016-2019 E. Matilda Ziegler Foundation for the Blind: PI
Role of Runx1 in retinopathy of prematurity
$240,000
Retinopathy of prematurity or ROP is a sight threatening disease that affects the most vulnerable members of our population: low birth weight preterm infants. ROP is characterized by the formation of irregular blood vessels and scar tissue within the eye, which can lead to permanent damage of the retina, the delicate light sensing film that lines the back of the eye. The primary treatment option for ROP is destruction of the peripheral retina with ablative laser. There is currently no FDA-approved medical treatment for ROP. Dr. Kim and colleagues hypothesize that Runx1 plays a critical and specific role in the development of ROP. This work may be the foundation of novel medically based treatments for ROP.

Publications

H-index

11 (Google Scholar, as of May 2017)

Selected Publications

Dr. Kim has published more than 30 peer-reviewed articles. Below is a list of selected publications. View his publications on PubMed, Google Scholar, or ORCID.

  1. Amarnani D, Machuca-Parra AI, Wong LL, Marko CK, Stefater JA, Stryjewski TP, Eliott D, Arboleda-Velasquez JF, Kim LA. Effect of Methotrexate on an In Vitro Patient-Derived Model of Proliferative Vitreoretinopathy. Invest Ophthalmol Vis Sci. 2017;58:3940-3949
  2. Ung C, Sanchez AV, Shen L, Davoudi S, Ahmadi T, Navarro-Gomez D, Chen CJ, Hancock H, Penman A, Hoadley S, Consugar M, Restrepo C, Shah VA, Arboleda-Velasquez JF, Sobrin L, Gai X, Kim LA.Whole exome sequencing identification of novel candidate genes in patients with proliferative diabetic retinopathy. Vision Res. 2017 May 9.
  3. Lam JD, Oh DJ, Wong LL, Amarnani D, Park-Windhol C, Sanchez AV, Cardona-Velez J, McGuone D, Stemmer-Rachamimov AO, Eliott D, Bielenberg DR, van Zyl T, Shen L, Gai X, D'Amore PA, Kim LA, Arboleda-Velasquez JF. Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis. Diabetes. 2017 Jul;66(7):1950-1956
  4. Wong LL, Lee NG, Amarnani D, Choi CJ, Bielenberg DR, Freitag SK, D'Amore PA, Kim LA. Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease: An Analysis of Vascular Growth Factors with Clinical Correlation. Ophthalmology. 2016 Sep;123(9):2028-36
  5. Pennock S, Kim LA, Kazlauskas A. Vascular Endothelial Cell Growth Factor A Acts via Platelet-Derived Growth Factor Receptor alpha To Promote Viability of Cells Enduring Hypoxia. Mol Cell Biol. 2016;36:2314-2327.