J Neurosci 9, 19771984 (1989). Patient 6 is a 19-year-old otherwise healthy man with a heterozygous c.905A>C; p.D302A mutation, whose best corrected vision is unknown (Table1). The state with the most residents by this name is California, followed by New York and Maryland. generated iPSC-RPE cells and helped write the paper; A.K. Solution osmolarity was between 310 and 315. The New England journal of medicine 358, 22312239 (2008). 62/833,069. HEK293 cells cultured on 6-cm dishes were co-transfected with pBacman-BEST1(WT)-CFP-myc and pBacman-BEST1(mutant or WT)-YFP-His at 1:1 ratio using PolyJet In Vitro DNA Transfection Reagent (SignaGen Laboratories, SL100688) following the manufacturers standard protocol. View Actual Score Check Background . 151: 2015: S4). We have marriage records for 25 people named Tingting Yang. Our results showed that these mutations are all loss-of-function with complete or partial deficiency of channel activity, while some of them affect the subcellular localization and/or Ca2+-sensitivity of BEST1. 2c,d), which contains multiple residues (e.g. August 22, 2022 - Present. Robust and effective T cell immune surveillance and cancer immunotherapy require properly allocating metabolic resources to sustain energetically costly processes, including growth and cytokine production. Google Scholar. Mao, H. et al. & Steinberg, R. H. Direct evidence for a basolateral membrane Cl- conductance in toad retinal pigment epithelium. (i) Current densities at 1.2 M [Ca2+]i in patient-derived iPSC-RPEs supplemented with WT BEST1 on AAV2 viruses. Immunoblotting results showed that the exogenous BEST1 expression level is comparable to that of the endogenous BEST1 (Supplementary Fig. Petrukhin, K. et al. Tingting YANG | Cited by 1,170 | of Dalian Maritime University, Dalian | Read 87 publications | Contact Tingting YANG Photos. She received her PhD in Biomedical Engineering from Johns Hopkins University School of Medicine and her postdoctoral training at Columbia University Medical Center. Patient-specific mutations impair BESTROPHIN1s essential role in mediating Ca2+-dependent Cl- currents in human RPE. Department of Control and Computer Engineering Connect with experts in your field Join ResearchGate to contact this researcher and. Keep track of how much of Tingting Yangs work you have seen. Yang, T. et al. PubMed CAS Skin biopsy samples were obtained from the healthy control donor and patients, and processed and cultured as previously described46. Series resistance was usually 1.52.5M. Seeing the Light after 25 Years of Retinal Gene Therapy. University of Rochester, +1 more The Johns Hopkins University, +1 more . Elife, https://doi.org/10.7554/eLife.29914 (2017). 20: 2021: 17-estradiol promotes acute refeeding in hungry mice via membrane . D203A, I205T and Y236C), which significantly enhance BEST1 channel activity25. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. (b) Representative current traces recorded from R218H iPSC-RPE (patient #2) supplemented with WT BEST1-GFP at 1.2 M [Ca2+]i. She is currently a Professor with Peng Cheng Laboratory, Shenzhen, China. But first, you must download and install it on your smartphone. 0 Add Rating Anonymously. Moreover, it is largely unclear how the Cl- channel function of hBest1 is regulated/activated. Tingting DING | Cited by 59 | of Beijing Institute of Technology, Beijing (BIT) | Read 13 publications | Contact Tingting DING The RPE status of the cells was confirmed by morphological signatures including intracellular pigment and hexagonal shape (Fig. HEK293 cells expressing BEST1 mutants displayed significantly smaller currents than WT at 1.2 M [Ca2+]i (Fig. CAS All error bars in this figure represent s.e.m. n=56 for each point. The WT plot was fitted to the Hill equation. S5), suggesting a complete loss of BEST1 channel activity in these mutants. Progress in retinal and eye research. You can find where a person works for free by using the Radaris mobile app. Title. Club career. Get what matters in translational research, free to your inbox weekly. PubMed Central Patient 1, a 6-year-old otherwise healthy girl with a heterozygous c.28G>A; p.A10T mutation, showed reduced visual acuities at 20/80 and 20/125 in the right and left eye, respectively (Table1). In addition to well-established classical mature RPE markers (Bestrophin1, CRALBP and RPE65), two more markers (PAX6 and MITF) were also used to validate the RPE fate of the cells. After thorough washing of the beads, bound fractions were eluted in 1x SDS sample buffer (Biorad, 1610747) by heating for 10min at 75C. Physiol Rev 88, 639672 (2008). Yang, Tingting; Liu, Qun; Kloss, Brian et al. Importantly, gene augmentation therapy also has great potential to treat other inherited disorders in the retina, such as autosomal dominant retinitis pigmentosa (adRP), which can be caused by mutations in over 25 known genes including RHO and RPE6538. Yang, Tingting University of Rochester, Rochester, NY, United States Abstract Many physiological events, such as heart beat and muscle contraction, are orchestrated by the cellular concentrations of certain ions, which flow in and out of the cell through designated structures on the cell membrane called ion channels. Interestingly, a third dominant mutation in that report, A164K, was not responsive to gene augmentation, probably attributed to structural instability as suggested by the authors36. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Data supporting the findings of this manuscript are available from the corresponding author upon reasonable request. After thorough washing, coverslips were mounted onto ProLong Diamond Antifade Mountant (Thermo Fisher Scientific, P36966). Tingting Yang's phone number is (859) 309-2295. Using the CytoTune-iPS 2.0 Sendai Reprogramming Kit (Thermo Fisher Scientific, A16517), donor-provided skin fibroblasts were reprogrammed into pluripotent stem cells (iPSCs). CAS Kemp, C. M., Jacobson, S. G., Roman, A. J., Sung, C. H. & Nathans, J. Abnormal rod dark adaptation in autosomal dominant retinitis pigmentosa with proline-23-histidine rhodopsin mutation. The vitelliform macular dystrophy protein defines a new family of chloride channels. Other Tingting Yang's; Trusted Connections, Since 2002. Marmorstein, A. D. et al. This work was supported by NIH grant EY025290 and GM127652 to T.Y. Using an EPC10 patch clamp amplifier (HEKA Electronics) controlled by Patchmaster (HEKA), whole-cell recordings were conducted 2472hours after splitting of RPE cells or transfection of HEK293 cells. This proposal is aimed to understand the structure and working mechanisms of hBest1 chloride channel, and the results will provide novel knowledge and principles for both basic research and biomedical applications. S1). The vitelliform material in her right eye displayed hyper-autofluorescence in fundus autofluorescence imaging and was detected in the macular area by OCT (Fig. Yan Zhong. 2g). & Mao, H. Gene augmentation for adRP mutations in RHO. Molecular therapy: the journal of the American Society of Gene Therapy 23, 18051809 (2015). Collectively, our results illustrate the physiological influence of these six dominant mutations on RPE surface Ca2+-dependent Cl current and the BEST1 channel function, provide structural insights into their disease-causing mechanisms, and demonstrate the rescue of BEST1 function in iPSC-RPE via gene supplementation. All iPSC lines were passaged every 36 days while maintained in mTeSR-1 medium (STEMCELL Technologies, 05850). Moreover, the rescue efficacy of Ca2+-dependent Cl currents in iPSC-RPEs bearing BEST1 dominant mutations was comparable to that in a previously reported iPSC-RPE with a recessive P274R mutation (Fig. Calmodulin regulation of TMEM16A and 16B Ca(2+)-activated chloride channels. Nuclei were detected by Hoechst staining. Patients underwent OCT and color fundus photography52,53. Ming-Ting Yang, PT, M.Sc Ph.D. Yang, T., Suhail, Y., Dalton, S., Kernan, T. & Colecraft, H. M. Genetically encoded molecules for inducibly inactivating CaV channels. Director: The River. n=56 for each point. Application number: Provisional Patent Application No. Make your IMDb page stand out by adding a demo reel. Article Bottom, Ca2+-dependent current densities, n=56 for each point, compared to WT (). Three-year follow-up after unilateral subretinal delivery of adeno-associated virus in patients with Leber congenital Amaurosis type 2. Possible relatives for Tingting Yang include Jimmy Yang, Zhenda Yang, Wei Manhua and several others. In particular, five mutants (A10T, R218H, L234P, Q293K and D302A) yielded tiny currents with no significant difference from untransfected cells (Fig. Mutations in the unfolded protein response regulator ATF6 cause the cone dysfunction disorder achromatopsia. Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years. Identification of the gene responsible for Best macular dystrophy. : University of Rochester, Rochester, NY, United States. To obtain the Key Laboratory of Optical Fiber Sensing and Communications Connect with experts in your field Join. Tingting has rich work experience spanning public and private sectors in diplomacy, education, and NGOs, creative, automotive, and consumer goods industries. S2). 2g)25,26. She is a mother, a . Google Scholar. Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium. We have marriage records for 25 people named Tingting Yang. 4ce and Supplementary Fig. (g) Comparison of current densities in iPSC-RPEs with WT or mutant BEST1 at 1.2 M [Ca2+]i, n=56. Wu, T. H. et al. Tingting Yang is a Nurse Practitioner in Hartford, CT. Find Yang's phone number, address and more. View Tingting Yang's professional profile on LinkedIn. However, since the vast majority of known BEST1 mutations are autosomal dominant, it remains a critical question whether the dominant mutant allele should be purposely suppressed during therapeutic intervention. Hyper-autofluorescence of yellowish subretinal vitelliform deposits were observed in both maculae areas (Fig. 1.83 3.76 /5. Our results showed that virus-mediated WT BEST1 gene supplementation restores the diminished Ca2+-dependent Cl currents in patient-derived iPSC-RPEs with the same dose- and time- dependent efficacy regardless of the mutation type (dominant vs. recessive) or deficiency level (null vs. partial), providing one of the first lines of evidence that BEST1 dominant mutations are rescuable by WT gene augmentation without the need of disrupting/suppressing the mutant allele. S3), where cells expressing WT BEST1 conducted peak current amplitude20. Davidson, A. E. et al. Structure and selectivity in bestrophin ion channels. Kane Dickson, V., Pedi, L. & Long, S. B. Methods Mol Biol 1353, 7788 (2016). Investigation and Restoration of BEST1 Activity in Patient-derived RPEs with Dominant Mutations. Yang, Tingting; Justus, Sally; Li, Yao et al. American journal of human genetics 82, 1931 (2008). As another inherited retinal disorder clearly linked to the mutation of a single gene, bestrophinopathy represents an attractive target of gene therapy. volume9, Articlenumber:19026 (2019) Data are presented as means s.e.m51. (g) The effect of replacing A243 and L234. It takes another 68 weeks in culture for them to form a functional monolayer, which would thenbe ready for function assays. Ion channels control the ion flux in and out of the cells, and thus play an essential role in physiology and pathology. The iPSCs from all the subjects enrolled in this study were characterized by detecting four standard pluripotency markers (SSEA4, Tra-1-60, SOX2 and Nanog). The human bestrophin-1 (hBest1) is a chloride (Cl-) conducting channel highly expressed in eyes. The healthy control donor (WT BEST1) and patients (mutant BEST1) all underwent a complete ophthalmic examination by a retinal physician in the Department of Ophthalmology, Columbia University Medical Center/New York Presbyterian Hospital. Li, Y. et al. Proc Natl Acad Sci USA 99, 40084013 (2002). Moreover, both dominant and recessive mutations of BEST1 are rescuable at a similar efficacy, and both BV and AAV can be used as the vector for gene delivery. : From day 29 on, the differentiation medium without Activin-A supplementation was used again until differentiation was completed. There are 40+ professionals named "Tingting Yang", who use LinkedIn to exchange information, ideas, and opportunities. Y He, T Yang, P Xu, Y Yang, X Cai, J Wang, H Liu, M Yu, . 2a and Supplementary Fig. Then, Alexa Fluor 488 conjugated donkey anti-mouse IgG (Thermo Fisher Scientific, A-21202) and Alexa Fluor 647 conjugated donkey anti-rabbit IgG (Thermo Fisher Scientific, A-31573) were diluted in blocking solution and incubated with cells at room temperature for 1h. Unbound secondary antibody was washed away with PBS thrice. ADS Moreover, the L234P mutant may have a highly flexible structure around the mutation site due to consecutive proline residues. PolyJet transfection reagent (SignaGen SL100688) was utilized to transfect HEK293 cells with plasmids bearing the WT BEST1 or desired mutant (1 g). Screening and large-scale expression of membrane proteins in mammalian cells for structural studies. LOW HIGH. Top, representative current traces recorded at 1.2 M [Ca2+]i. The American journal of pathology 187, 517527 (2017). The membranes were incubated in blocking buffer containing 5% (w/v) non-fat milk for 1hour at room temperature, and subsequently incubated overnight at 4C in blocking buffer supplemented with primary antibody. C.J. edited themanuscript; Y.F. In principle, the excess of WT BEST1 could overwhelm the mutant BEST1 despite the latter being dominant over the former at a 1:1 ratio. We speculate that there are RPE-specific facilitating factor(s) of BEST1. (e) Fundus infrared reflectanceimage and SDOCT of a WT left eye. Nature genetics 19, 241247 (1998). S1). Google Scholar. 5i), providing a proof-of-concept for curing BEST1-associated retinal degenerative diseases in both dominant and recessive cases by AAV-mediated gene augmentation. 2015 Grantome : Steady-state current density recorded at+100mV plotted vs. free [Ca2+]i; n=56 for each point. Radaris.com allows you to reverse search a phone number, email, or the address of the person you are interested in to obtain a detailed report about them. Top, representative current traces recorded at 1.2 M [Ca2+]i. Inset, voltage protocol used to elicit currents. Her EOG testing consisted of noisy background, and there was a decrease of light rise in both eyes (Supplementary Fig. All data offered isderived from public sources. Plano, TX Brookline, MA Dallas, TX Frisco, TX Worcester, MA, Jui-sen Yang, Jason Yang, Jimmy Yang, Juei-mao Yang, Jui-jen Yang, Liting Yang, Yueh Yang, Li-shang Yang, Ellen Yang, University of North Texas @acs Lab, Kurtz & Company P.C, 4100 Accounting System, Cost Accounting, Troy, MI Detroit, MI Madison Heights, MI, Santa Ana, CA Huntington Beach, CA Costa Mesa, CA Irvine, CA, Guang Yang, Katherine Sohn, Taesung Yang, Theresa Yang, Annie Yang, Chuck Yang, Ling Yang, Alice Yang, Stephen Yang, Experian Ltd, Nuvision Federal Credit Union, Financial Freedom Senior Funding Corp., A subsidiary of IndyMac Bank, Att Systems, Toshiba Corporation, California Polytechnic State University-San Luis Obispo, California State Polytechnic University-pomona, Chanel, Volunteers, Ver Unica, May's Flower Shop, Maison Du Soleil, Mango, Academy of Art University, City College of San Francisco, Haslett, MI East Lansing, MI Okemos, MI, Bachelors, Bachelor of Business Administration, Logistics, Business Administration, Management, Supply Chain Management, Finance, Doctorates, Doctor of Philosophy, Microbiology, Philosophy. The right macula had subretinal fibrosis. Google Scholar. A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement. Columbia University Business Data 621 Dodge Hall, New York, NY 10027, New York City (212) 854-3825 hh276@columbia.edu Rescue of patient-derived iPSC-RPEs by WT BEST1 supplementation. September 11, 2021 - April 30, 2022. Patient 4, a 61-year-old otherwise healthy woman with a heterozygous c.728G>A; p.A243T mutation, showed reduced visual acuity at 20/100 in the right eye (Table1). Article Statistical analyses were conducted using built-in functions in Origin. High titer AAV2 virus (11012 GC/ml) bearing a CMV promoter driven BEST1-T2A-GFP expression cassette was purchased from Applied Biological Materials. Articles Cited by Public access. BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure. On the other hand, while RPE65 is mainly associated with LCA, a D477G mutation in it has been linked to adRP44. & Hartzell, H. C. Regulation of bestrophin Cl channels by calcium: role of the C terminus. 0 Reputation Score Range. designed experiments, analyzed data, made figures and wrote the paper. However, the rescue efficacy of gene augmentation for BEST1 dominant mutations is still unknown. (e) Current densities at 1.2 M [Ca2+]i in a second clone of R218H iPSC-RPE supplemented with different dosages of WT BEST1-GFP on BacMam viruses. All types of bestrophinopathies, except for ARB, result from autosomal dominant mutation of BEST1. (c) Current densities in R218H iPSC-RPE supplemented with WT BEST1-GFP (blue triangle) at 1.2 M [Ca2+]i, compared to those from un-supplemented R218H (red triangle) and WT () iPSC-RPEs. Background was subtracted by the rolling ball method in Fiji with a radius of 50 pixels. (c) Ribbon diagram of two oppositely facing (144) protomers of a BEST1 pentamer are shown with the extracellular side on the top. (d) Ca2+-dependent current densities in R218H iPSC-RPE supplemented with WT BEST1-GFP (blue triangle) compared to those from WT () iPSC-RPE. (ac) Fundus infrared reflectanceimage and Spectral Domain Optical Coherence Tomography (SDOCT) of the maculae from patient 1 (a), patient 2 (b) and patient 3 (c), right and left eyes, respectively. LinkedIn is the world's largest business network, helping professionals like Tingting Yang discover inside connections to recommended job . performed patch clamp, confocal microscopy, immunoblotting, co-IP and analyzed data, Y.L. Fujii, S., Gallemore, R. P., Hughes, B. Subcellular localization of WT and mutant BEST1 in iPSC-RPEs. Yang, T., He, L. L., Chen, M., Fang, K. & Colecraft, H. M. Bio-inspired voltage-dependent calcium channel blockers. Since then she has been taking up various roles in film and TV production, including as a Director, Director of Photography and Production Manager. View Tingting Yang's profile on LinkedIn, the world's largest professional community.
Splendora Isd Bell Schedule,
U20 Soccer Teams Near Me,
Articles T
