Bradley Gelfand

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Primary Appointment

Associate Professor of Ophthalmology, Ophthalmology

Education

  • BS, University of Iowa
  • PhD, Biomedical Engineering, University of Virginia

Research Disciplines

Biomedical Engineering, Biotechnology, Cardiovascular Biology, Experimental Pathology, Immunology, Molecular Biology, Neuroscience, Physiology

Research Interests

Blinding disease age-related macular degeneration, utilizing the tools of immunology, molecular biology, and engineering.

Research Description

One major focus of our work is to study the cellular and molecular consequences of the blood supply in the eye. Specifically, we are interested in quantifying the biomechanical changes that occur in the choroidal vasculature in healthy and diseased eyes, and how these micro-environmental cues affect the biology and pathology of the eye. To accomplish this, we perform high-resolution 3-D microscopy to generate accurate maps of the human choroidal anatomy in health and in disease which is utilized for computational fluid dynamic modeling. To study the influence of choroidal hemodynamics on ocular health, we employ a sophisticated cell culture system which is capable of reproducing the hemodynamic environment of the human eye.

Training

  • Basic Cardiovascular Research Training Grant
  • Biotechnology Training Grant

Selected Publications

2023

An, S., Yu, H., Islam, M. D. M., Zhang, X., Zhan, Y., Olivieri, J. J., . . . Gelfand, B. D. (2023). Effects of donor-specific microvascular anatomy on hemodynamic perfusion in human choriocapillaris. SCIENTIFIC REPORTS, 13(1). doi:10.1038/s41598-023-48631-2

Gelfand, B. D., Argyle, D. A., Olivieri, J. J., & Ambati, J. (2023). Survey of commercial antibodies targeting Y chromosome-encoded genes.. MedComm - Future medicine, 2(4), e62. doi:10.1002/mef2.62

2022

Huang, P., Narendran, S., Pereira, F., Fukuda, S., Nagasaka, Y., Apicella, I., . . . Ambati, J. (2022). Subretinal injection in mice to study retina physiology and disease. NATURE PROTOCOLS, 17(6), 1468-+. doi:10.1038/s41596-022-00689-4

Huang, P., Narendran, S., Pereira, F., Fukuda, S., Nagasaka, Y., Apicella, I., . . . Ambati, J. (2022). The Learning Curve of Murine Subretinal Injection Among Clinically Trained Ophthalmic Surgeons. TRANSLATIONAL VISION SCIENCE & TECHNOLOGY, 11(3). doi:10.1167/tvst.11.3.13

Palko, S. I., Saba, N. J., Mullane, E., Nicholas, B. D., Nagasaka, Y., Ambati, J., . . . Mohan, R. (2022). Compartmentalized citrullination in Muller glial endfeet during retinal degeneration. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 119(9). doi:10.1073/pnas.2121875119

Ropp, A., Frazier, A. A., Gelfand, B., & Jeudy, J. (2022). The Dean Effect: An Aortic Arch Flow Artifact Mimicking Dissection. RADIOLOGY-CARDIOTHORACIC IMAGING, 4(1). doi:10.1148/ryct.210229

2021

Wang, S. -B., Narendran, S., Hirahara, S., Varshney, A., Pereira, F., Apicella, I., . . . Ambati, J. (2021). DDX17 is an essential mediator of sterile NLRC4 inflammasome activation by retrotransposon RNAs. SCIENCE IMMUNOLOGY, 6(66). doi:10.1126/sciimmunol.abi4493

Banerjee, D., Langberg, K., Abbas, S., Odermatt, E., Yerramothu, P., Volaric, M., . . . Kerur, N. (2021). A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling. NATURE COMMUNICATIONS, 12(1). doi:10.1038/s41467-021-26240-9

Ambati, M., Apicella, I., Wang, S. -B., Narendran, S., Leung, H., Pereira, F., . . . Gelfand, B. D. (2021). Identification of fluoxetine as a direct NLRP3 inhibitor to treat atrophic macular degeneration. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 118(41). doi:10.1073/pnas.2102975118

Fukuda, S., Narendran, S., Varshney, A., Nagasaka, Y., Wang, S. -B., Ambati, K., . . . Ambati, J. (2021). Alu complementary DNA is enriched in atrophic macular degeneration and triggers retinal pigmented epithelium toxicity via cytosolic innate immunity. SCIENCE ADVANCES, 7(40). doi:10.1126/sciadv.abj3658

Narendran, S., Pereira, F., Yerramothu, P., Apicella, I., Wang, S. -B., Ambati, K., . . . Ambati, J. (2021). Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-β induced retinal pigmented epithelium degeneration. SIGNAL TRANSDUCTION AND TARGETED THERAPY, 6(1). doi:10.1038/s41392-021-00537-z

Fukuda, S., Varshney, A., Fowler, B. J., Wang, S. -B., Narendran, S., Ambati, K., . . . Ambati, J. (2021). Cytoplasmic synthesis of endogenous Alu complementary DNA via reverse transcription and implications in age-related macular degeneration. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 118(6). doi:10.1073/pnas.2022751118

2020

Ambati, J., Magagnoli, J., Leung, H., Wang, S. -B., Andrews, C. A., Fu, D., . . . Gelfand, B. D. (2020). Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development. NATURE COMMUNICATIONS, 11(1). doi:10.1038/s41467-020-18528-z

Narendran, S., Pereira, F., Yerramothu, P., Apicella, I., Wang, S. -B., Varshney, A., . . . Ambati, J. (2020). A Clinical Metabolite of Azidothymidine Inhibits Experimental Choroidal Neovascularization and Retinal Pigmented Epithelium Degeneration. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 61(10). doi:10.1167/iovs.61.10.4

Makin, R. D., Argyle, D., Hirahara, S., Nagasaka, Y., Zhang, M., Yan, Z., . . . Gelfand, B. D. (2020). Voluntary Exercise Suppresses Choroidal Neovascularization in Mice. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 61(5). doi:10.1167/iovs.61.5.52

Wright, C. B., Uehara, H., Kim, Y., Yasuma, T., Yasuma, R., Hirahara, S., . . . Gelfand, B. D. (2020). Chronic Dicer1 deficiency promotes atrophic and neovascular outer retinal pathologies in mice. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 117(5), 2579-2587. doi:10.1073/pnas.1909761117

2018

Makin, R. D., Apicella, I., Nagasaka, Y., Kaneko, H., Turner, S. D., Kerur, N., . . . Gelfand, B. D. (2018). RF/6A Chorioretinal Cells Do Not Display Key Endothelial Phenotypes. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 59(15), 5795-5802. doi:10.1167/iovs.18-25215

Kerur, N., Fukuda, S., Banerjee, D., Kim, Y., Fu, D., Apicella, I., . . . Ambati, J. (2018). cGAS drives noncanonical-inflammasome activation in age-related macular degeneration (vol 24, pg 50, 2017). NATURE MEDICINE, 24(1). Retrieved from https://www.webofscience.com/

2017

Kerur, N., Fukuda, S., Banerjee, D., Kim, Y., Fu, D., Apicella, I., . . . Ambati, J. (2018). cGAS drives noncanonical-inflammasome activation in age-related macular degeneration. NATURE MEDICINE, 24(1), 50-+. doi:10.1038/nm.4450

2016

Gelfand, B. D., & Ambati, J. (2016). A Revised Hemodynamic Theory of Age-Related Macular Degeneration. TRENDS IN MOLECULAR MEDICINE, 22(8), 656-670. doi:10.1016/j.molmed.2016.06.009

Bogdanovich, S., Kim, Y., Mizutani, T., Yasuma, R., Tudisco, L., Cicatiello, V., . . . Ambati, J. (2016). Human IgG1 antibodies suppress angiogenesis in a target-independent manner. SIGNAL TRANSDUCTION AND TARGETED THERAPY, 1. doi:10.1038/sigtrans.2015.1

Yasuma, R., Cicatiello, V., Mizutani, T., Tudisco, L., Kim, Y., Tarallo, V., . . . Ambati, J. (2016). Intravenous immune globulin suppresses angiogenesis in mice and humans. SIGNAL TRANSDUCTION AND TARGETED THERAPY, 1. doi:10.1038/sigtrans.2015.2

2015

Mizutani, T., Fowler, B. J., Kim, Y., Yasuma, R., Krueger, L. A., Gelfand, B. D., & Ambati, J. (2015). Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56(12), 7122-7129. doi:10.1167/iovs.15-17440

Gelfand, B. D., Wright, C. B., Kim, Y., Yasuma, T., Yasuma, R., Li, S., . . . Ambati, J. (2015). Iron Toxicity in the Retina Requires Alu RNA and the NLRP3 Inflammasome. CELL REPORTS, 11(11), 1686-1693. doi:10.1016/j.celrep.2015.05.023

Gelfand, B. D., Wright, C. B., & Ambati, J. (2015). A novel mouse model of neovascular AMD due to Dicer1 deficiency. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56(7). Retrieved from https://www.webofscience.com/

2014

Hirano, Y., Yasuma, T., Mizutani, T., Fowler, B. J., Tarallo, V., Yasuma, R., . . . Ambati, J. (2014). IL-18 is not therapeutic for neovascular age-related macular degeneration. NATURE MEDICINE, 20(12), 1372-1375. doi:10.1038/nm.3671

Fowler, B. J., Gelfand, B. D., Kim, Y., Kerur, N., Tarallo, V., Hirano, Y., . . . Ambati, J. (2014). Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity. SCIENCE, 346(6212), 1000-1003. doi:10.1126/science.1261754

Kim, Y., Tarallo, V., Kerur, N., Yasuma, T., Gelfand, B. D., Bastos-Carvalho, A., . . . Ambati, J. (2014). DICER1/Alu RNA dysmetabolism induces Caspase-8-mediated cell death in age-related macular degeneration. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(45), 16082-16087. doi:10.1073/pnas.1403814111

2013

Kerur, N., Hirano, Y., Tarallo, V., Fowler, B. J., Bastos-Carvalho, A., Yasuma, T., . . . Ambati, J. (2013). TLR-Independent and P2X7-Dependent Signaling Mediate Alu RNA-Induced NLRP3 Inflammasome Activation in Geographic Atrophy. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 54(12), 7395-7401. doi:10.1167/iovs.13-12500

Ambati, J., Atkinson, J. P., & Gelfand, B. D. (2013). Immunology of age-related macular degeneration. NATURE REVIEWS IMMUNOLOGY, 13(6), 438-451. doi:10.1038/nri3459

Feaver, R. E., Gelfand, B. D., & Blackman, B. R. (2013). Human haemodynamic frequency harmonics regulate the inflammatory phenotype of vascular endothelial cells. NATURE COMMUNICATIONS, 4. doi:10.1038/ncomms2530

2012

Dridi, S., Hirano, Y., Tarallo, V., Kim, Y., Fowler, B. J., Ambati, B. K., . . . Ambati, J. (2012). ERK1/2 activation is a therapeutic target in age-related macular degeneration. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 109(34), 13781-13786. doi:10.1073/pnas.1206494109

Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., . . . Ambati, J. (2012). DICER1 Loss and Alu RNA Induce Age-Related Macular Degeneration via the NLRP3 Inflammasome and MyD88. CELL, 149(4), 847-859. doi:10.1016/j.cell.2012.03.036

2011

Kleinman, M. E., Kaneko, H., Cho, W. G., Dridi, S., Fowler, B. J., Blandford, A. D., . . . Ambati, J. (2012). Short-interfering RNAs Induce Retinal Degeneration via TLR3 and IRF3. MOLECULAR THERAPY, 20(1), 101-108. doi:10.1038/mt.2011.212

Gelfand, B. D., Meller, J., Pryor, A. W., Kahn, M., Bortz, P. D. S., Wamhoff, B. R., & Blackman, B. R. (2011). Hemodynamic Activation of β-Catenin and T-Cell-Specific Transcription Factor Signaling in Vascular Endothelium Regulates Fibronectin Expression. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 31(7), 1625-U366. doi:10.1161/ATVBAHA.111.227827

Kaneko, H., Dridi, S., Tarallo, V., Gelfand, B. D., Fowler, B. J., Cho, W. G., . . . Ambati, J. (2011). DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. NATURE, 471(7338), 325-+. doi:10.1038/nature09830

2010

Feaver, R. E., Gelfand, B. D., Wang, C., Schwartz, M. A., & Blackman, B. R. (2010). Atheroprone Hemodynamics Regulate Fibronectin Deposition to Create Positive Feedback That Sustains Endothelial Inflammation. CIRCULATION RESEARCH, 106(11), 1703-1U86. doi:10.1161/CIRCRESAHA.109.216283