Research interests: Ocular stem cell and translational research
Contact Information: Email 301-451-9372
10 Center Drive
Bethesda, Maryland 20892
Dr. Bharti holds a bachelor's degree in biophysics from the Panjab University in Chandigarh, India, where he graduated with highest honors. This was followed by a master degree in biotechnology at the Maharaja Sayaji Rao University in Baroda, India and a diploma in molecular cell biology at the Johann Wolfgang Goethe University at Frankfurt in Germany. Supported by an international Ph.D. student fellowship, he obtained his Ph.D. from the same institution, graduating summa cum laude. His Ph.D. work involved basic biology in the areas of heat stress, cellular chaperones, and epigenetics. From Germany, Dr. Bharti came to the National Institute of Neurological Disorders and Stroke to work with Dr. Heinz Arnheiter as a postdoctoral fellow. While there, he published numerous papers in the areas of transcription factor regulation, pigment cell biology, and the developmental biology of the eye. It is perhaps this combination of diverse backgrounds that led him to develop an interest in the emerging field of stem cell biology, particularly of the retinal pigment epithelium, as he moved into the role of staff scientist. Dr. Bharti has authored numerous publications and has won several awards, including, most recently, being a finalist in the prestigious trans-NIH Earl Stadtman Symposium.
The goal of the Unit on Ocular Stem Cells and Translational Research (OSCTR) 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 throughput drug screens, and to develop cell-based therapy for retinal degenerative diseases.
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.
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.
Bharti K, Rao M, Hull SC, Stroncek D, Brooks BP, Feigal E, van Meurs JC, Huang CA, Miller SS. Developing cellular therapies for retinal degenerative diseases. Invest Ophthalmol Vis Sci. 2014;55(2):1191-202.
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.
Song MJ, Bharti K. Looking into the future: Using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling. Brain Res. 2016;1638(Pt A):2-14.
Miyagishima KJ, Wan Q, Miller SS, Bharti K. A basis for comparison: sensitive authentication of stem cell derived RPE using physiological responses of intact RPE monolayers. Stem Cell Transl Investig. 2017;4.