Inherited eye disease research center

Our Vision

Our research goal is to understand the molecular mechanisms underlying human diseases caused by genetic mutations, with a special emphasis on inherited eye diseases. With these mechanistic insights, we develop novel and specific therapeutics by utilizing high-throughput drug screening approaches.

Our Team

  • Dr. Moshe Giladi - Lab PI, Physician, Internal Medicine D;Dept. of Physiology and Pharmacology

  • Ruba Yehia, Ph.D. student
  • Bar Manori, M.Sc. student
  • Suha Abed Alkader, M.Sc. student

  • Dr. Yoni Haitin, Ph.D. Dept. of Physiology and Pharmacology, Tel Aviv University.

Research

of DHDDS-related retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common inherited form of retinal degeneration, ultimately leading to blindness. Despite the major advancements in elucidating the genetic causes for RP, it remains incurable to date. In recent years, a growing number of disease-causing mutations in DHDDS were identified, leading to diverse clinical presentations including RP and severe neurological diseases. We have determined the atomic-resolution structure of the enzymatic complex in which DHDDS is involved and use this information to investigate its function in health and disease, as well as to develop targeted therapies for RP.

translational protein modifications

Post-translational protein modifications (PTM) are crucial for protein folding, function, and cellular localization in every cell in the human body. These modifications were highlighted in cancerous transformation, metastasis, and response to treatments. However, no specific treatments targeting aberrant PTM are currently available for clinical use. By studying key enzymes involved in the synthesis of moieties for PTM, we use a structure-guided approach to develop novel and specific cancer therapies.

Highlight Publications

Proton-modulated interactions of ions with transport sites of prokaryotic and eukaryotic NCX prototypes.

Refaeli B, Liu S, Hiller R, Giladi M, Baiz CR, Khananshvili D.

Cell Calcium. 2021 Nov;99:102476.

Two de novo GluN2B mutations affect multiple NMDAR-functions and instigate severe pediatric encephalopathy.

Kellner S, Abbasi A, Carmi I, Heinrich R, Garin-Shkolnik T, Hershkovitz T, Giladi M, Haitin Y, Johannesen KM, Steensbjerre Møller R, Berlin S.

Elife. 2021 Jul 2;10:e67555.

Structural basis of heterotetrameric assembly and disease mutations in the human cis-prenyltransferase complex.

Bar-El ML, Vaňková P, Yeheskel A, Simhaev L, Engel H, Man P, Haitin Y, Giladi M.

Nat Commun. 2020 Oct 19;11(1):5273.

Convulsive seizures and some behavioral comorbidities are uncoupled in the Scn1aA1783V Dravet syndrome mouse model.

Fadila S, Quinn S, Turchetti Maia A, Yakubovich D, Ovadia M, Anderson KL, Giladi M, Rubinstein M.

Epilepsia. 2020 Oct;61(10):2289-2300.


Conserved cysteine dioxidation enhances membrane interaction of human Cl–intracellular channel 5.

Ferofontov A, Vankova P, Man P, Giladi M, Haitin Y.

FASEB J. 2020 Aug;34(8):9925-9940.

Structure of KCNH2 cyclic nucleotide-binding homology domain reveals a functionally vital salt-bridge.

Ben-Bassat A, Giladi M, Haitin Y.

J Gen Physiol. 2020 Apr 6;152(4):e201912505.

Hydrogen-Deuterium Exchange Mass-Spectrometry of Secondary Active Transporters: From Structural Dynamics to Molecular Mechanisms.

Giladi M, Khananshvili D.

Front Pharmacol. 2020 Feb 19;11:70.

Structure-affinity insights into the Na+ and Ca2+ interactions with multiple sites of a sodium-calcium exchanger.

Iwaki M, Refaeli B, van Dijk L, Hiller R, Giladi M, Kandori H, Khananshvili D.

FEBS J. 2020 Nov;287(21):4678-4695.

Structural Characterization of Full-Length Human Dehydrodolichyl Diphosphate Synthase Using an Integrative Computational and Experimental Approach.

Lisnyansky Bar-El M, Lee SY, Ki AY, Kapelushnik N, Loewenstein A, Chung KY, Schneidman-Duhovny D, Giladi M, Newman H, Haitin Y.

Biomolecules. 2019 Oct 28;9(11):660.

Metal Coordination Is Crucial for Geranylgeranyl Diphosphate Synthase-Bisphosphonate Interactions: A Crystallographic and Computational Analysis.

Lisnyansky M, Yariv E, Segal O, Marom M, Loewenstein A, Ben-Tal N, Giladi M, Haitin Y.

Mol Pharmacol. 2019 Nov;96(5):580-588.

Structure-dynamic and functional relationships in a Li+-transporting sodium‑calcium exchanger mutant.

Giladi M, Lee SY, Refaeli B, Hiller R, Chung KY, Khananshvili D.

Biochim Biophys Acta Bioenerg. 2019 Mar 1;1860(3):189-200.

Reduced Activity of Geranylgeranyl Diphosphate Synthase Mutant Is Involved in Bisphosphonate-Induced Atypical Fractures.

Lisnyansky M, Kapelushnik N, Ben-Bassat A, Marom M, Loewenstein A, Khananshvili D, Giladi M, Haitin Y.

Mol Pharmacol. 2018 Dec;94(6):1391-1400.

Key residues controlling bidirectional ion movements in Na+/Ca2+ exchanger.

van Dijk L, Giladi M, Refaeli B, Hiller R, Cheng MH, Bahar I, Khananshvili D.

Cell Calcium. 2018 Dec;76:10-22.

Inherent flexibility of CLIC6 revealed by crystallographic and solution studies.

Ferofontov A, Strulovich R, Marom M, Giladi M, Haitin Y.

Sci Rep. 2018 May 2;8(1):6882.

The Crystal Structure and Conformations of an Unbranched Mixed Tri-Ubiquitin Chain Containing K48 and K63 Linkages.

Padala P, Soudah N, Giladi M, Haitin Y, Isupov MN, Wiener R.

J Mol Biol. 2017 Dec 8;429(24):3801-3813.

Overexpression and Purification of Human Cis-prenyltransferase in Escherichia coli.

Edri I, Goldenberg M, Lisnyansky M, Strulovich R, Newman H, Loewenstein A, Khananshvili D, Giladi M, Haitin Y.

J Vis Exp. 2017 Aug 3;(126):56430.

Dynamic distinctions in the Na+/Ca2+ exchanger adopting the inward- and outward-facing conformational states.

Giladi M, van Dijk L, Refaeli B, Almagor L, Hiller R, Man P, Forest E, Khananshvili D.

J Biol Chem. 2017 Jul 21;292(29):12311-12323.

Structure-based dynamic arrays in regulatory domains of sodium-calcium exchanger (NCX) isoforms.

Giladi M, Lee SY, Ariely Y, Teldan Y, Granit R, Strulovich R, Haitin Y, Chung KY, Khananshvili D. 

Sci Rep. 2017 Apr 20;7(1):993.

Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli.

Giladi M, Edri I, Goldenberg M, Newman H, Strulovich R, Khananshvili D, Haitin Y, Loewenstein A.

Protein Expr Purif. 2017 Apr;132:138-142.
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