Bikash R. Pattnaik, PHD

Pubmed

More information:

• Dr. Pattnaik’s McPherson Eye Reseach Institute’ webpage

Research Description:

Understand the mechanism of Kir7.1 mutations associated blindness using patient derived iPS-Retinal Pigment Epithelium cells. Kir7.1 potassium channels are present in the apical processes of RPE cell that mediate ionic homeostasis within the retina structure and several mutations are associated with childhood blindness. Our primary goal is to restore functional Kir7.1 channel in patient derived iPS-RPE cells either through gene delivery or using various drugs targeting rectification of mutant channel. iPS-RPE cells give advantageous access to patients for drug and gene trial so that translation from bench to bed side is quick. We use whole cell electrophysiology for characterizing Kir7.1 current in these cells and immunohistochemistry and biochemical protocol are informative of protein expression quantitation. In another project our goal is to determine the function of bestrophin. Bestrophin was cloned from RPE cells and in heterologous system was demonstrated as a Cl- channel. Several other investigations showed that it can also function as a mediator of cell calcium. Using Best’s disease patient derived iPS-RPE cells we are trying to model the true function of bestrophin in its most natural environment.

Selected References:

• Shahi PK, Hermans D, Sinha D, Brar S, Moulton H, Stulo S, Borys KD, Capowski E, Pillers DM, Gamm DM, Pattnaik BR. Gene Augmentation and Readthrough Rescue Channelopathy in an iPSC-RPE Model of Congenital Blindness. Am J Hum Genet. 2019 Feb 7;104(2):310-318. doi: 10.1016/j.ajhg.2018.12.019. Epub 2019 Jan 24. PMID:30686507
• Phillips MJ, Jiang P, Howden S, Barney P, Min J, York NW, Chu LF, Capowski EE, Cash A, Jain S, Barlow K, Tabassum T, Stewart R, Pattnaik BR, Thomson JA, Gamm DM. A Novel Approach to Single Cell RNA-Sequence Analysis Facilitates In Silico Gene Reporting of Human Pluripotent Stem Cell-Derived Retinal Cell Types. Stem Cells. 2018 Mar;36(3):313-324. doi: 10.1002/stem.2755. Epub 2017 Dec 25. Erratum in: Stem Cells. 2018 Jul;36(7):1133. PMID:29230913
• Singh R, Shen W, Kuai D, Martin JM, Guo X, Smith MA, Perez ET, Phillips MJ, Simonett JM, Wallace KA, Verhoeven AD, Capowski EE, Zhang X, Yin Y, Halbach PJ, Fishman GA, Wright LS, Pattnaik BR, Gamm DM. iPS cell modeling of Best disease: insights into the pathophysiology of an inherited macular degeneration. Hum Mol Genet. 2013 Feb 1;22(3):593-607. doi: 10.1093/hmg/dds469. Epub 2012 Nov 8. PMID:23139242
• Meyer JS, Howden SE, Wallace KA, Verhoeven AD, Wright LS, Capowski EE, Pinilla I, Martin JM, Tian S, Stewart R, Pattnaik BR, Thomson JA, Gamm DM. Optic vesicle-like structures derived from human pluripotent stem cells facilitate a customized approach to retinal disease treatment. Stem Cells. 2011 Aug;29(8):1206-18. doi: 10.1002/stem.674. PMID:21678528