ד"ר יהונתן חייטין רובינשטיין

  • סגל אקדמי בכיר בפיזיולוגיה ופרמקולוגיה
פיזיולוגיה ופרמקולוגיה סגל אקדמי בכיר
ניווט מהיר:
ד"ר יהונתן חייטין רובינשטיין
טלפון פנימי: 03-6409261
טלפון נוסף: 03-6409894
פקס: 03-6409894
משרד: רפואה-סאקלר, 532

מחקר

STRUCTURAL PERSPECTIVE OF ION CHANNELS MODULATION

Ion channels are intricate membrane-embedded molecular machines, which enable cells to communicate with their surroundings by allowing and maintaining crucial ionic flow across the plasma membrane. Diverse activation and regulatory mechanisms render these specialized proteins perfectly engineered for communicating a wide array of incoming signals into precisely orchestrated electrical-cellular responses.

At the Haitin lab, part of the Sackler School of Medicine, we focus on understanding how ion channels structures are funneled into their specialized activities. Specifically, we are interested in the emerging roles of ion channels in shaping the immune response, and in their contribution to facilitated cellular proliferation observed in cancerous transformation. To do so, we use a wide array of cutting-edge approaches, which include structural biology techniques, electrophysiology, fluorescence spectroscopy and high-throughput cancer-related mutant functional screens.

As ion channels are of immense importance for human health, with emerging pivotal roles in cancer biology, our comprehensive efforts to unveil utmost basic mechanisms underlying ion channels activity should provide novel insights into their regulation and may prove beneficial for future development of novel therapeutic strategies.

Funding:

  • 2018-2019       Shtacher Award for Biomedical Research in Pharmacology
  • 2017-2018       Instruct R&D Award
  • 2016-2019       Israel Cancer Research Fund (ICRF), Research Career Development Award
  • 2016-2020       Israel Science Foundation, Personal Grant
  • 2016-2017       German-Israeli Foundation for Scientific Research and Development (GIF), Young Scientists Program Grant
  • 2016-2018       Recanati Foundation for Biomedical Research Grant
  • 2015-2020       Member, The I-CORE on Integrated Structural Cell Biology

Awards and Prizes

Lisnyansky M., Kapelushnik N., Ben-Bassat A., Marom M., Loewenstein A., Khananshvili D., Giladi M.*, Haitin Y.* (2018) Bisphosphonates inhibition of GGPS1 mutant underlies Atypical Femoral Fractures. Submitted.

 

Ferofontov A., Strulovich R., Marom M., Giladi M., Haitin Y. (2018) Inherent flexibility of CLIC6 revealed by crystallographic and solution studies. Sci Rep., Accepted for publication.

 

Meisel E., Tobelaim W., Dvir M., Haitin Y., Peretz A., Attali B. (2018) Inactivation gating of Kv7.1 channels does not involve concerted cooperative subunit interactions. Channels, 12, 89–99.

 

Mashahreh B., Hassouna F., Soudah N., Cohen-Kfir E., Strulovich R, Haitin Y., Wiener R. (2018) Trans -binding of UFM1 to UBA5 stimulates UBA5 homodimerization and ATP binding. The FASEB Journal, In press.

 

Padala P., Soudah N., Giladi M., Haitin Y., Isupov M.N., Wiener R. (2017) The Crystal Structure and Conformations of an Unbranched Mixed Tri-Ubiquitin Chain Containing K48 and K63 Linkages. Journal of Molecular Biology429, 3801–3813.

 

Tobelaim W.S., Dvir M., Lebel G., Cui M., Buki T., Peretz A., Marom M., Haitin Y., Logothetis D.E., Hirsch J.A., Attali B. (2017). Ca2+-Calmodulin and PIP2 interactions at the proximal C-terminus of Kv7 channels. Channels., 11, 686-695.

 

Edri I., Goldenberg M., Lisnyansky M., Strulovich R., Newman H., Loewenstein A., Khananshvili D., Giladi M., Haitin Y. (2017) Overexpression and purification of human Cis-prenyltransferase in Escherichia coli. J Vis Exp.2017.

 

Giladi M., Lee S.Y., Ariely Y., Teldan Y., Granit R., Strulovich R., Haitin Y., Chung K.Y. and Khananshvili D. (2017). Structure-encoded dynamics of regulatory diversity in sodium-calcium exchanger (NCX) isoforms. Sci Rep., 7, 993.

 

James Z.M., Borst A.J., Haitin Y., Frenz B., Dimaio F., Zagotta W.N. and Veesler D. (2017). Allosteric Regulation of a Cyclic Nucleotide-Gated Ion Channel Visualized by CryoEM. PNAS114, 4430-4435.

 

Giladi M.*, Edri I., Goldenberg M., Newman H., Strulovich R., Khananshvili D., Haitin Y.*, Loewenstein A. (2017). Purification and characterization of human dehydrodolychil diphosphate synthase (DHDDS) overexpressed in E. coli. Protein Expr Purif., 132, 138-142. *Co-corresponding author.

 

Tobelaim W.S., Dvir M., Lebel G., Cui M., Buki T., Peretz A., Marom M.Haitin Y., Logothetis D.E., Hirsch J.A., Attali B. (2017). Competition of calcified calmodulin N lobe and PIP2 to an LQT mutation site in Kv7.1 channel. PNAS, 114, E869–E878.

 

Dvir M., Peretz A., Haitin Y., Attali B. (2014). Recent molecular insights from mutated IKS channels in cardiac arrhythmia. Curr Opin Pharmacol., 15C, 74-82.

 

Haitin Y. (2014). A 'funny' cyclic dinucleotide receptor. Nat Chem Biol., 10, 413-414.

 

Dvir M., Strulovich M., Sachyani D., Ben-Tal Cohen I., Haitin Y., Dessauer C., Pongs O., Kass R., Hirsch J.A. & Attali B. (2014). Long QT mutations at the interface between KCNQ1 helix C and KCNE1 disrupt IKS regulation by PKA and PIP2. J Cel Sci., 127, 3943-3955.

 

Haitin Y., Carlson A.E. & Zagotta W.N. (2013). Structural mechanism for regulation of KCNH channels by the eag domain. Nature, 501, 444-448.

 

Shuart N.G., Haitin Y., Camp S.S., Black K.D. & Zagotta W.N. (2011). Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels. Nat Commun., 2, 457.

 

Meisel E., Dvir M., Haitin Y., Giladi M., Peretz A. & Attali B. (2012). KCNQ1 channels do not undergo concerted but sequential gating transitions in both the absence and the presence of KCNE1 protein. J Biol Chem., 287, 34212-34224.

 

Peretz A., Pell L., Gofman Y., Haitin Y., Samger L., Patrich E., Kornilov P., Gourgy-Hacohen O., Ben-Tal N. & Attali B. (2010). Targeting the voltage sensor of Kv7.2 voltage gated K+ channels with a new gating-modifier. PNAS, 107,15637-15642.

 

Haitin Y., Wiener R., Shaham D., Peretz A., Cohen E.B., Shamgar L., Pongs O., Hirsch J.A. & Attali B. (2009). Intracellular domains interactions and gated motions of I(KS) potassium channel subunits. EMBO J., 28, 1994-2005.

 

Haitin Y. & Attali B. (2008). The C-terminus of Kv7 channels: a multifunctional module. J Physiol., 586, 1803-1810.

 

Haitin Y., Yisharel I., Malka E., Shamgar L., Schottelndreier H., Peretz A., Paas Y. & Attali B. (2008). S1 constrains S4 in the voltage sensor domain of Kv7.1 K+ channels. PLoS ONE, 3, e1935.

 

Shamgar L., Haitin Y., Yisharel I., Malka E., Schottelndreier H., Peretz A., Paas Y. & Attali B. (2008). KCNE1 constrains the voltage sensor of Kv7.1 K+ channels. PLoS ONE, 3, e1943.

 

Wiener R., Haitin Y., Shamgar L., Fernandez-Alonso M. C., Martos A., Chomsky-Hecht O., Rivas G., Attali B. & Hirsch J. A. (2008). The KCNQ1 (Kv7.1) COOH terminus, a multitiered scaffold for subunit assembly and protein interaction. J Biol Chem., 283, 5815-5830.

 

Shamgar L., Ma L., Schmitt N., Haitin Y., Peretz A., Wiener R., Hirsch J., Pongs O. & Attali B. (2006). Calmodulin is essential for cardiac IKS channel gating and assembly: impaired function in long-QT mutations. Circ Res., 98, 1055-1063.

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