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<span>Ocular and Stem Cell Translational Research Section</span>
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<h2>About our work</h2>
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<p>Dysfunctions in the RPE are thought to be the initiating events leading to degenerative eye diseases. Therefore, a better understanding of the disease initiating pathways in RPE will provide a basis for therapeutic interventions. In collaboration with the NEI clinic, we are obtaining skin biopsies from patients with clinically diagnosed degenerative eye diseases. These biopsies are being used to derive iPS cells. RPE cells differentiated from such iPS cells are used to study events that have led to disease initiation and progression.</p><p>In collaboration with National Center for Advancing Translational Sciences (NCATS), we have combined the patient-specific iPSC approach with high throughput screening assays performed in 384-well plates to identify novel compounds that could act as potential therapeutic agents. In collaboration with new NIH Center for Regenerative Medicine, we are developing iPSC-derived RPE tissue for cell-based therapy. We have modified the existing stem cell to RPE differentiation protocols to make them more complaint with current Good Manufacturing Practices (cGMP-work).</p><p>Our work uses the most cutting edge technologies in the field and aims to translate these technologies to a clinical use.</p>
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Our research mission
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<p>The goal of the Ocular and Stem Cell Translational Research Section is to perform translational research on degenerative eye diseases using induced pluripotent stem (iPS) cell technology. We are using this technology to develop in vitro disease models to study patient-specific disease processes, to set up high through drug screens, and to develop cell-based therapy for retinal degenerative disease.</p><p>Our translational goals are focused on retinal pigment epithelium (RPE), a monolayer of highly polarized cells located in the back of the eye, whose apical processes inter-digitate with photoreceptor outer segments. RPE performs several functions that are absolutely critical for the health and integrity of photoreceptors. Some of these functions include regulating nutrient and metabolite flow, maintaining ionic homeostasis in the sub-retinal space, regenerating visual pigment, and phagocytizing shed photoreceptor outer segments.</p>
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<h2>Selected publications</h2>
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<p>Schaub, N.J., Hotaling, N.A., Manescu, P., Padi, S., Wan, A., Sharma, R., Chalfoun, J., Simon, M., Ouladi, M., Simon, Jr., C.G., Bajcsy, P., and <strong>Bharti, K.</strong> (2020) <a href="https://pubmed.ncbi.nlm.nih.gov/31714897/">Deep Learning Predicts Function of Live Retinal Pigment Epithelium from Quantitative Microscopy.</a> <em>J. Clinical Investigations</em>130: 1010-1023.</p><p>Sharma, R., Khristov, V., Rising, A., Jha,B.S., Dejene, R., Hotaling, N., Li, Y., Stoddard,J., Stankewicz,C., Wan, Q., Zhang, C., Campos, M.M., Miyagishima, K.J., McGaughey, D., Villasmil, R., Mattapallil, M., Stanzel, B., Qian, H., Wong, W., Chase, L., Charles, S., McGill, T., Miller, S., Maminishkis, A., Amaral, J., and <strong>Bharti, K.</strong>, (2019) <a href="https://pubmed.ncbi.nlm.nih.gov/30651323/"><strong>Clinical-grade Stem Cell–derived Retinal Pigment Epithelium Patch Rescues Retinal Degeneration in Rodents and Pigs.</strong></a> <em>Science Translational Medicine</em> <strong>11</strong>, eaat5580 (2019) 1-13.</p><p>Miyagishimaa, K., Wan, Q., Corneo, Q., Sharma, R., Lotfi, M., Boles, N., Hua, F., Maminishkis, A., Zhang, C., Blenkinsop, T., Khristov, V., Jha, B., Memon, O., D’Souza, S., Temple, S., Miller, S., <strong>Bharti, K.</strong> (2016) <a href="https://pubmed.ncbi.nlm.nih.gov/27400791/">In Pursuit of Authenticity: iPS Cell-derived RPE for Clinical Applications.</a> <em>Stem Cells Translational Medicine <strong>5 (11) 1562-1574.</strong></em></p><p>Hotaling, N.A., Jeon, J., Wade, M.B., Luong, D., Palmer, X-L., <strong>Bharti, K.</strong>, and Simon, C.G. (2016) <a href="https://pubmed.ncbi.nlm.nih.gov/27907145/">Training to Improve Precision and Accuracy in the Measurement of Fiber Morphology</a>. <em>PLoSOne 11 (12): e01676664. </em></p><p>George, A., Zand, D.J., Hufnagel, R.B., Sharma, R., Sergeev, Y., Legare, J.M., Rice, G.M., Schwoerer, J.A., Rius, M., Gamm, D.M., <strong>Bharti, K.*</strong>, and Brooks, B.P. (2016) COMMAD: a Novel Syndrome Caused by Biallelic Mutation of the MITF Gene. <em>Am. J. Hum. Genet. 99 (6): 1388-1394. *Co-senior author.</em></p><p>Keir, L.S., Firth, R., Aponik, L., Feitelberg, D., Sakimoto, S., Aguilar, E., Welsh, G.I., Richards, A., Usui, Y., Satchell, S.C., Kuzmuk, V., Coward, R.J., Goult, J., Bull, K.R., Sharma, R., <strong>Bharti, K.,</strong> Westenskow, P.D., Michael, I.P., Saleem, M.A., and Friedlander, M., (2016) <a href="https://pubmed.ncbi.nlm.nih.gov/27918307/">VEGF regulates local inhibitory complement proteins in the eye and kidney.</a><em> J. Clin. Investigations (epubl. Dec ). </em></p><p>Hotaling, N.A., <strong>Bharti, K.</strong>, Kriel, H., and Simon, C.G. (2015) <a href="https://pubmed.ncbi.nlm.nih.gov/26043061/">Validated open source nanofiber diameter measurement tool.</a> <em>Biomaterials </em><strong>61:</strong> 327-338.</p><p>Maruotti, J., Sripathi, S.R., <strong>Bharti, K.</strong>, Fuller, J., Wahlin, K., Ranganathan, V., Sluch, V., Berlinicke, C., Davis, J., Kim, C., Zhao, L., Wan, J., Qian, J., Corneo, B., Temple, S., Dubey, R., Olenyuk, B., Bhutto, I., Lutty, G., and Zack, D.J., (2015) <a href="https://pubmed.ncbi.nlm.nih.gov/26269569/">Small molecule directed efficient generation of retinal pigment epithelium from human pluripotent stem cells.</a> <em>PNAS</em> <strong>112 (35)</strong>: 10950-10955<em>. </em></p><p>Hotaling, N.A., <strong>Bharti, K.</strong>, Kriel, H., and Simon, C.G. (2015) <a href="https://pubmed.ncbi.nlm.nih.gov/26380840/">Dataset for the validation and use of DiameterJ an open source nanofiber diameter measurement tool.</a> <em>Data In Brief <strong>5:</strong> 13-22.</em></p><p>Blenkinsop, T.A., Saini, J.S., Maminishkis, A., <strong>Bharti, K.,</strong> Wan, Q., Banzon, T., Lotfi, M., Davis, J., Singh, D., Rizzolo, L.J., Miller, S., Temple, S., and Stern, J.H. (2015) <a href="https://pubmed.ncbi.nlm.nih.gov/26540654/">Human Adult Retinal Pigment Epithelial Stem Cell-derived RPE Monolayers Exhibit Key Physiological Characteristics of Native Tissue.</a> <em>IOVS <strong>56 (12):</strong> 7085-7099.</em></p><p>Greer, Y.E., Westlake, C.J., Gao, B., <strong>Bharti, K.</strong>, Kim, K., Shiba, Y., Sokol, S., Yang, Y., and Rubin, J. (2014) <a href="https://pubmed.ncbi.nlm.nih.gov/24648492/">Casein kinase 1 delta is a mediator of ciliogenesis.</a> <em>Mol. Biol. Cell </em><strong>25 (10):</strong> 1629-1640.</p><p>Raviv, S., <strong>Bharti, K.</strong>, Rencus-Lazar, S., Cohen-Tayar, Y., Schyr, R., Evantal, N., Meshorer, Zilberberg, A.E., Reubinoff, B., Grebe, R., Rosin-Arbesfeld, R., Lauderdale, J., Lutty, G., Arnheiter, H., Ashery-Padan, R., (2014) <a href="https://pubmed.ncbi.nlm.nih.gov/24875170/">PAX6 regulates melanogenesis in the retinal pigment epithelium through feed-forward regulatory interactions with MITF.</a> <em>PLoS Genetics </em><strong>10 (5):</strong> e1004360<em>. </em></p><p>Ferrer, M., Corneo, B., Davis, J., Wan, Q., Miyagishima, K.J., King, R., Maminishkis, A., Marugan, J., Sharma, R., Shure, M., Temple, S., Miller, S., and <strong>Bharti, K.</strong> (2014) <a href="https://pubmed.ncbi.nlm.nih.gov/24873859/">A multiplex high-throughput gene expression assay to simultaneously detect disease and functional markers in induced pluripotent stem cell-derived retinal pigment epithelium.</a> <em>Stem Cells Translational Medicine </em><strong>3</strong>:1-12.</p><p>Nasonkin, I., Merbs, S., Lazo, K., Oliver, V., Brooks, M., Patel, K., Enke, R., Nellissery, J., Jamrich, M., Le, Y., <strong>Bharti, K.</strong>, Rachel, R., Fariss, R., Zack, D., Rodriguez-Boulan, E., Swaroop, A. (2013) <a href="https://pubmed.ncbi.nlm.nih.gov/23406904/">Conditional knockdown of DNA methyltransferase-1 (Dnmt1) reveals a key role of retinal pigment epithelium in mammalian photoreceptor differentiation.</a> <em>Development </em><strong>140:</strong> 1330-1341.</p><p>Ou, J., <strong>Bharti, K.</strong>, Nodari, A., Bertuzzi, S., and Arnheiter, H. (2013) <a href="https://pubmed.ncbi.nlm.nih.gov/23555005/"><em>Vax1/2</em> genes counteract <em>Mitf</em>-induced respecification of the retinal pigment epithelium.</a> <em>PLoSOne</em> <strong>8 (3):</strong> e59247.</p><p>Yan, Y., Shin, S., Jha, B, Liu, Q., Shen, J., Zhan, M., Davis, J., <strong>Bharti, K.</strong>, Zeng, X., Rao, M., Malik, N., and Vemuri, M. (2013) <a href="https://pubmed.ncbi.nlm.nih.gov/24113065/">Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.</a> <em>Stem Cells Translational Medicine </em><strong>2 (11): </strong>862-870.</p><p>Forni, P., <strong>Bharti, K.</strong>, Flannery, E., Shimogori, T., and Wray, S. (2013) <a href="https://pubmed.ncbi.nlm.nih.gov/24336726/">The indirect role of FGF8 in defining neurogenic niches of the olfactory/GnRH systems.</a> <em>J. Neuroscience </em><strong>33 (50)</strong>: 19620-19634.</p>
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<div class="c-section" id="section-id-12463">
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<h3 class="c-section__heading">
|
||
|
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Reviews and chapters
|
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<div class="c-text">
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<p>Sharma, R., Bose, D., Maminishkis, A., and <strong>Bharti, K.</strong> (2020). <a href="https://pubmed.ncbi.nlm.nih.gov/31914900/">Retinal Pigment Epithelium Replacement Therapy for Age-Related Macular Degeneration: Are We There Yet?</a> <em>Ann. Rev. Tox. Pharm.</em> 60:553-572<em>.</em></p><p>Jha, B.S., Farnoodian, M., and <strong>Bharti, K.</strong> (2020). <a href="https://pubmed.ncbi.nlm.nih.gov/32946199/">Regulatory considerations for developing a phase I investigational new drug application for autologous pluripotent stem-cells based therapy product.</a> <em>Stem Cells Transl. Med.</em> Epub.</p><p>Singh, M., Park, S., Albini, T. A., Canto-Soler, M. V., Klassen, H., MacLaren, R.E., Nagiel, A., Schwartz, S.D., <strong>Bharti, K.</strong> (2019) <a href="https://pubmed.ncbi.nlm.nih.gov/31494256/">Retinal Stem Cell Transplantation – Balancing Safety and Potential.</a> <em>Prog. Exp. Eye Res. </em>75:100779<em>.</em></p><p>Miyagishima, K.J., Wan, Q., Miller, S.S., and <strong>Bharti, K.</strong> (2017) <a href="https://pubmed.ncbi.nlm.nih.gov/28286868/">A Basis for Comparison: Sensitive Authentication of Stem Cell Derived RPE Using Physiological Responses of Intact RPE Monolayers.</a> <em>Stem Cell & Translational Investigation. </em><strong>4: </strong>e1497.</p><p>Hotaling, N.A., Khristov, V., Wan, Q., Sharma, R., Jha, B.S., Lotfi, M., Maminishkis, A., Simon, C.G., and <strong>Bharti, K.</strong> (2016) <a href="https://pubmed.ncbi.nlm.nih.gov/27110730/">Nanofiber Scaffold Based Tissue Engineered Retinal Pigment Epithelium to Treat Degenerative Eye Diseases.</a> <em>Journal of Ocular Pharmacology and Therapeutics. </em><strong>32 (5): </strong>272-285.</p><p>Jha, S.B. and <strong>Bharti, K.</strong> (2015) <a href="https://pubmed.ncbi.nlm.nih.gov/26146605/">Regenerating retinal pigment epithelial cells to cure blindness: a road towards personalized artificial tissue.</a> <em>Current Stem Cell Reports. </em><strong>1 (2): </strong>79-91.</p><p>Song, M.J. and <strong>Bharti, K.</strong> (2015) <a href="https://pubmed.ncbi.nlm.nih.gov/26706569/">Looking into the future: using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling.</a> <em>Brain Research. </em><strong>1638 (Part A):</strong> 2-14.</p><p><strong>Bharti, K.*,</strong> Rao, M., Hull, S.C., Stroncek, D., Brooks, B.P., Feigal, E., van Meurs, J.C., Huang, C.A., and Miller, S. (2014) <a href="https://pubmed.ncbi.nlm.nih.gov/24573369/">Developing cellular therapies for retinal degenerative diseases.</a> <em>IOVS </em><strong>55 (2)</strong>: 1191-1202<em>. </em>*<strong>Corresponding author</strong></p><p><strong>Bharti, K.*,</strong> Miller, S.S., and Arnheiter, H. (2011) <a href="https://pubmed.ncbi.nlm.nih.gov/20846177/">The new paradigm: Retinal pigment epithelium cells generated from embryonic stem cells or induced pluripotent stem cells.</a> <em>Pig. Cell Melanoma Res.</em> <strong>24:</strong> 21-34. *<strong>Corresponding author</strong></p><p><strong>Bharti, K.</strong>, Nguyen, M., Skuntz, S., Bertuzzi, S., and Arnheiter, H. (2006) The other pigment cell—the pigment epithelium of the eye. <em>Pig. Cell Res. </em><strong>19:</strong> 380-394.</p>
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<div class="c-group__staff-list c-section" id="key-staff">
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<h2>Ocular and Stem Cell Translational Research Section key staff</h2>
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<div class="views-element-container">
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<div class="js-view-dom-id-170aa38dcaeda5f7b40d283649d1dab70a08f78d33be18899722e9607db90786 lab-staff">
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<th id="view-title-table-column" class="views-field views-field-title" scope="col">Name</th>
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<th id="view-field-email-table-column" class="views-field views-field-field-email" scope="col">Email</th>
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<th id="view-field-phone-table-column" class="views-field views-field-field-phone" scope="col">Phone</th>
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<td headers="view-title-table-column" class="views-field views-field-title"><a href="/research/research-labs-and-branches/we-are-nei-intramural/kapil-bharti" hreflang="en">Kapil Bharti, Ph.D.</a> </td>
|
||
<td headers="view-field-lab-staff-title-table-column" class="views-field views-field-field-lab-staff-title">Senior Investigator </td>
|
||
<td headers="view-field-email-table-column" class="views-field views-field-field-email"><a href="mailto:kapilbharti@nei.nih.gov">kapilbharti@nei.nih.gov</a> </td>
|
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<td headers="view-field-phone-table-column" class="views-field views-field-field-phone">301-451-9372 </td>
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<div class="c-group__staff-list c-section" id="alumni-staff">
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|
||
<div class="js-view-dom-id-0b35e3f04e5fbf4f0abb1bf2499982bd3e7885cd3a16f237094df0213afe45a6 lab-alumni">
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<div class="c-filter js-view-dom-id-dc6dda1d6b45db30747175ff9a520e4d2dea824d80ac65f54f670752a6332eae news-page news-page--block_5">
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<h2 class="c-filter__heading">News from this lab</h2>
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||
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<div class="c-sidebar-widget__list-item views-row">
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<div class="c-teaser">
|
||
<div class="c-teaser__image">
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||
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||
<img loading="lazy" src="/sites/default/files/styles/thumbnail/public/2024-12/Eye%20diagram.jpg?itok=duYzL-7o" width="200" height="200" alt="Eye illustration" />
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<div class="c-teaser__content">
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<h3 class="c-teaser__header">
|
||
<a class="c-teaser__link" href="/about/news-and-events/news/arpa-h-announces-funding-development-eye-transplantation">
|
||
ARPA-H announces funding for development of eye transplantation
|
||
</a>
|
||
</h3>
|
||
<p class="c-teaser__date">
|
||
<time datetime="2024-12-02T17:21:22-05:00">December 2, 2024</time>
|
||
</p>
|
||
<div class="c-teaser__summary">
|
||
ARPA-H announced the teams to receive awards from its Transplantation of Human Eye Allografts (THEA) program.
|
||
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<div class="c-sidebar-widget__list-item views-row">
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<div class="c-teaser">
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<div class="c-teaser__image">
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||
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||
<img loading="lazy" src="/sites/default/files/styles/thumbnail/public/2024-07/Bharti%20and%20Sharma%20-1.jpg?itok=WXKdfXLA" width="200" height="200" alt="decorative" />
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<div class="c-teaser__content">
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<h3 class="c-teaser__header">
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||
<a class="c-teaser__link" href="/about/news-and-events/news/nih-researchers-discover-potential-therapeutic-target-degenerative-eye-disease">
|
||
NIH researchers discover potential therapeutic target for degenerative eye disease
|
||
</a>
|
||
</h3>
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||
<p class="c-teaser__date">
|
||
<time datetime="2024-07-26T17:28:48-04:00">July 26, 2024</time>
|
||
</p>
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||
<div class="c-teaser__summary">
|
||
Researchers from the National Institutes of Health (NIH) have discovered the source of dysfunction in the process whereby cells in the eye's retina remove waste.
|
||
</div>
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<div class="c-sidebar-widget__list-item views-row">
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<div class="c-teaser">
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<div class="c-teaser__image">
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<img loading="lazy" src="/sites/default/files/styles/thumbnail/public/2024-03/Monocyte%20thumbnail%20for%20web.jpg?itok=ZFIqddER" width="200" height="200" alt="" />
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<div class="c-teaser__content">
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||
<a class="c-teaser__link" href="/about/news-and-events/news/monocyte-factory-help-scientists-study-immune-related-conditions-eye">
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||
'Monocyte factory' to help scientists study immune-related conditions of the eye
|
||
</a>
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The technique, known by the research team as a “monocyte factory,” makes possible a theoretically limitless source of human immune cells for research and the development of therapies for a variety of conditions including eye disease.
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<p class="views-element-container c-last-updated" id="block-views-block-nei-last-updated-block-1"><strong>Last updated:</strong> December 18, 2024</p>
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