Tingting Yang, PhD

Our Providers

Academic Appointments

  • Assistant Professor of Ophthalmic Sciences (in Ophthalmology)
Tingting Yang, PhD

The Yang lab primarily studies disease-associated ion channels in the eye. Ion channels are membrane proteins through which different ions flow in and out of the cell. There are many types of ion channels in human eyes, participating in various physiological functions such as neural signal transduction, metabolic waste removal and cell volume control. This underlies the pathological potential of ion channels dysregulation/disruption. For instance, Bestrophin1 (BEST1) is a calcium-activated chloride channel in retinal pigmented epithelium, and its over 250 genetic mutations cause a spectrum of vision threatening retinal degenerative disorders, including the early-onset form of vitelliform macular dystrophy, also known as Best disease.

Our research is generally focused on the structure and function of ion channels in the eye, and the pathological mechanism and treatment of their associated diseases. To tackle these challenges, we employ a multidisciplinary platform empowered by cryo-EM/X-ray crystallography, electrophysiology, CRISPR/Cas9-mediated genome editing and stem cell reprogramming/differentiation. Our previous accomplishments include solving the first structure of a bestrophin homolog, elucidating the physiological function and molecular mechanism of human BEST1, and establishing an iPSC-RPE cell based “disease-in-a-dish” model for BEST1 mutations. We have recently expanded our studies to Bestrophin2 (BEST2), another chloride channel (in the same membrane protein family as BEST1) involved in intraocular pressure control and a potential drug target for the treatment of glaucoma, and to the gene therapy of Best disease.

NIH Grants

  • THERAPEUTIC GENE EDITING AND MULTIMODAL IMAGING IN JUVENILE MACULAR DEGENERATION (Federal Gov)

    Jun 1 2020 - May 31 2025

    MECHANISTIC CHARACTERIZATION OF CALCIUM-ACTIVATED CHLORIDE CHANNELS IN RETINAL PIGMENT EPITHELIUM (Federal Gov)

    Sep 1 2019 - Mar 31 2023

    MECHANISTIC CHARACTERIZATION OF CALCIUM-ACTIVATED CHLORIDE CHANNELS IN RETINAL PIGMENT EPITHELIUM (Federal Gov)

    Sep 1 2019 - Mar 31 2023

    STRUCTURE-FUNCTION ANALYSIS OF BESTROPHINS (Federal Gov)

    May 1 2015 - Apr 30 2017

    NEW YORK STRUCTURAL BIOLOGY CENTER (Private)

    Aug 1 2010 - Jul 31 2015

    RESEARCH AGREEMENT WITH BROOKHAVEN NATIONAL LABS (Federal Gov)

    Feb 1 2009 - Jan 31 2014

    MOLECULAR DETERMINANTS OF L-TYPE CALCIUM CHANNEL GATING (Federal Gov)

    Apr 15 2002 - Jun 30 2013

Publications

  1. Owji AP, Zhao Q, Ji C, Kittredge A, Hopiavuori A, Fu Z, Ward N, Clarke OB, Shen Y, Zhang Y, Hendrickson WA, Yang T. Structural and functional characterization of the bestrophin-2 anion channel. Nat Struct Mol Biol, 2020; 27(4): 382-391
  2. Lima de Carvalho JR Jr, Kim HJ, Ueda K, Zhao J, Owji AP, Yang T, Tsang SH, Sparrow JR. Effects of deficiency in the RLBP1-encoded visual cycle protein CRALBP on visual dysfunction in humans and mice. J Biol Chem, 2020; 295(19): 6767-6780
  3. Ji C, Li Y, Kittredge A, Hopiavuori A, Ward N, Yao P, Fukuda Y, Zhang Y, Tsang SH, Yang T. Investigation and restoration of BEST1 activity in patient-derived RPEs with dominant mutations. Sci Rep, 2019; 9(1):19026
  4. Ji C, Kittredge A, Hopiavuori A, Ward N, Chen S, Fukuda Y, Zhang Y, Yang T. Dual Ca2+-dependent gates in human Bestrophin1 underlie novel disease-causing mechanisms of gain-of-function mutations. Commun Biol, 2019; Jun 24;2:240. doi: 10.1038/s42003-019-0433-3
  5. Zhang Y, Kittredge A, Ward N, Ji C, Chen S, Yang T. ATP activates bestrophin ion channels through direct interaction. Nat Commun, 2018; 9(1): 3126
  6. Kittredge A, Ji C, Zhang Y, Yang T. Differentiation, maintenance and analysis of human retinal pigment epithelium cells: a disease-in-a-dish model for BEST1 mutations. J Vis Exp, 2018; (138). doi:10.3791/57791
  7. Kittredge A, Ward N, Hopiavuori A, Zhang Y, Yang T. Expression and purification of mammalian Bestrophin ion channels. J Vis Exp, 2018; (138). doi:10.3791/57832
  8. Li Y, Zhang Y, Xu Y, Kittredge A, Ward N, Chen S, Tsang SH, Yang T. Patient-specific mutations impair BESTROPHIN1's essential role in mediating Ca2+-dependent Cl- currents in human RPE. eLife, 2017; Oct 24;6. pii: e29914
  9. Yang T, Colecraft HM. Calmodulin regulation of TMEM16A and 16B Ca2+-activated chloride channels. Channels, 2016; 10(1): 38-44
  10. Yang T, Justus S, and Li Y, Tsang SH. BEST1: the best target for gene and cell therapies. Molecular Therapy, 2015; 23(12): 1805-9
  11. Yang T#, Hendrickson WA#, Colecraft HM#. Preassociated apocalmodulin mediates Ca2+-dependent sensitization of activation and inactivation of TMEM16A/16B Ca2+-gated Cl- channels. PNAS, 2014; 111(51): 18213-8 (#corresponding authors)
  12. Yang T, Liu Q, Kloss B, Bruni R, Kalathur RC, Guo Y, Kloppmann E, Rost B, Colecraft HM, Hendrickson WA. Structure and selectivity in bestrophin ion channels. Science, 2014; 346(6207): 355-9
  13. Yang T, Colecraft HM. Regulation of voltage-dependent calcium channels by RGK proteins. Biochim Biophys Acta, 2013; 1828(7):1644-54
  14. Yang T, He LL, Chen M, Fang K, Colecraft HM. Bio-inspired voltage-dependent calcium channel blockers. Nat Commun, 2013; 4: 2540
  15. Yang T#, Puckerin A, Colecraft HM#. Distinct RGK GTPases differentially use a1- and auxiliary b- binding-dependent mechanisms to inhibit CaV1.2/CaV2.2 channels. PLoS One, 2012; 7(5):e37079 (#corresponding authors)
  16. Yang T, Xu X, Kernan T, Wu V, Colecraft HM. Rem, a member of the RGK GTPases, inhibits recombinant CaV1.2 channels using multiple mechanisms that require distinct conformations of the GTPase. J physiol, 2010; 588(Pt 10):1665-1681 (Cover Article)
  17. Yang T, Suhail Y, Dalton S, Kernan T, Colecraft HM. Genetically encoded molecules for inducibly inactivating CaV channels. Nat Chem Biol, 2007; 3(12):795-804 (Faculty of 1000 selection)

For a complete list of publications, please visit PubMed.gov