Kapil Bharti, Ph.D.
Ocular and Stem Cell Translational Research Unit
Building 10, Room 10B10
10 Center Drive
Bethesda, MD 20892
Our translational goals are focused on the 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. 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. In collaboration with 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 compliant with current Good Manufacturing Practices (cGMP-work). Our work uses the most cutting-edge technologies in the field and aims to translate these technologies to a clinical use.
Sharma R, Khristov V, Rising A, Jha BS, Dejene R, Hotaling N, Li Y, Stoddard J, Stankewicz C, Wan Q, Zhang C, Campos MM, Miyagishima KJ, McGaughey D, Villasmil R, Mattapallil M, Stanzel B, Qian H, Wong W, Chase L, Charles S, McGill T, Miller S, Maminishkis A, Amaral J, Bharti K. Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs. Sci Transl Med. 2019;11(475).
May-Simera HL, Wan Q, Jha BS, Hartford J, Khristov V, Dejene R, Chang J, Patnaik S, Lu Q, Banerjee P, Silver J, Insinna-Kettenhofen C, Patel D, Lotfi M, Malicdan M, Hotaling N, Maminishkis A, Sridharan R, Brooks B, Miyagishima K, Gunay-Aygun M, Pal R, Westlake C, Miller S, Sharma R, Bharti K. Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells. Cell Rep. 2018;22(1):189-205.
Creasey AA, Stacey G, Bharti K, Sato Y, Lubiniecki A. A strategic road map to filing a Biologics License Application for a pluripotent stem cell derived therapeutic product. Biologicals. 2019;59:68-71.
Ferrer M, Corneo B, Davis J, Wan Q, Miyagishima KJ, King R, Maminishkis A, Marugan J, Sharma R, Shure M, Temple S, Miller S, Bharti K. A multiplex high-throughput gene expression assay to simultaneously detect disease and functional markers in induced pluripotent stem cell-derived retinal pigment epithelium. Stem Cells Transl Med. 2014;3(8):911-22.
Bharti K, Gasper M, Ou J, Brucato M, Clore-Gronenborn K, Pickel J, Arnheiter H. A regulatory loop involving PAX6, MITF, and WNT signaling controls retinal pigment epithelium development. PLoS Genet. 2012;8(7):e1002757.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on September 1st, 2019