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Welcome to the Sklan Molecular Virology Lab

Positive-strand RNA viruses encompass over one-third of all virus genera and include numerous pathogens. These viruses replicate in the cytoplasm building their replication complexes on modified host intracellular membranes. Our major goal is to better understand the interactions of these pathogens with their host cells using Hepatitis C virus, dengue virus and Zika virus as our major models. We hope that our understanding of these viruses at the basic science level will contribute at the applied level as well.  

Projects in the lab

Mobirise



Mechanism of action of antiviral interferon stimulated genes.

Mobirise




Live cell imaging techniques to study viral-host interactions

Mobirise





Novel screens for the Identification of new viral-host interactions

Mobirise

Drug Resistance to viral hepatitis induced Hepatocelluar cacinoma 

Post-docs/MD research                         

Orly Ravid
Ofir Har-Noy

PhD Students

Namma David
Omer Stern
Inbar Nevo-Yassaf (Joint with Prof. Koret Hirschberg)

M.Sc Students

Taga Lerner
Michal Feldman (Joint With Prof. Rosin-Arbesfeld and Hershkovitz)
Rebu Varghese

Research Associates

Anna Dukhovny

Publications


2019
Lahav-Ariel L, Caspi M, Nadar-Ponniah P, Zelikson N, Hofmann I, Hanson K, Sklan EH, Franke W, Avraham KB, Rosin-Arbesfeld R. Striatin is a novel modulator of cell adhesion. FASEB J. 33(4):4729-4740

Dukhovny A, Lamkiewicz K, Chen Q, Fricke M, Jabrane-Ferrat N, Marz M, Jung JU, Sklan EH. A CRISPR activation screen identifies genes protecting from Zika virus infection. In press. J. Virol.

2018
Seo GJ, Kim C, Shin W, Sklan EH, Eoh H, Jung JU. TRIM56-mediated monoubiquitination of cGAS for cytosolic DNA sensing. Nature Communication, 9(1):613. 

Shirazi R, Ram D, Rakovsky A, Gozlan Y, Bucris E, Shaked-Mishan P, Picard O, Shemer-Avni Y, Ben-Zvi H, Halutz O, Lurie Y, Safadi R, Mendelson E. Sklan EH, Ben-Ari Z, Mor O. Hepatitis delta seroprevalence and molecular characterization of hepatitis B and delta coinfection in Israel. BMC Infectious Diseases. 18(1):97. 

Dukhovny A, Shlomai A, Sklan EH. The antiviral protein Viperin suppresses T7 polymerase mediated RNA synthesis–possible implications for its antiviral activity. Sci Rep. 88100.

2017
Nevo-Yassaf I, Lovelle M, Nahmias Y, Hirschberg K, Sklan EH. Live cell Imaging and analysis of lipid droplets biogenesis in HCV infected cells. Methods. S1046-2023(16)30491-1. 

2016
Levy G, Habib N, Guzzardi MA, Kitsberg D, Bomze D, Ezra E, Uygun BE, Uygun K, Trippler M, Schlaak JF, Shibolet O, Sklan EH, Cohen M, Timm J, Friedman N, Nahmias Y. Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection. Nat Chem Biol. 12(12):1037-1045. 

 Feldman M, Hershkovitz I, Sklan EH, Kahila Bar-Gal G, Pap I, Szikossy I, Rosin-Arbesfeld R. Detection of a Tumor Suppressor Gene Variant Predisposing to Colorectal Cancer in an 18th Century Hungarian Mummy. PLoS One. 11(2):e0147217. 

2015
Hung YF, Schwarten M, Hoffmann S, Willbold D, Sklan EH, Koenig B. Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes. Viruses. 21;7(7):4119-30.

Yaffe Y, Hugger I, Yassaf IN, Shepshelovitch J, Sklan EH, Elkabetz Y, Yeheskel A, Pasmanik-Chor M, Benzing C, Macmillan A, Gaus K, Eshed-Eisenbach Y, Peles E, Hirschberg K. The myelin proteolipid plasmolipin forms oligomers and induces liquid-ordered membranes in the Golgi complex. J Cell Sci. 128(13):2293-302. 

Hung YF, Schwarten M, Schünke S, Thiagarajan-Rosenkranz P, Hoffmann S, Sklan EH, Willbold D, Koenig BW. Dengue virus NS4A cytoplasmic domain binding to liposomes is sensitive to membrane curvature. Biochim Biophys Acta. 1848(5):1119-26. 

Cho NJ, Lee C, Pang PS, Pham EA, Fram B, Nguyen K, Xiong A, Sklan EH, Elazar M, Koytak ES, Kersten C, Kanazawa KK, Frank CW, Glenn JS. Phosphatidylinositol 4,5-bisphosphate is an HCV NS5A ligand and mediates replication of the viral genome. Gastroenterology. 148(3):616-25.

David N, Yaffe Y, Hagoel L, Elazar M, Glenn JS, Hirschberg K, Sklan EH. The interaction between the hepatitis C proteins NS4B and NS5A is involved in viral replication. Virology. 475:139-49. 

Levy G, Bomze D, Heinz S, Ramachandran SD, Noerenberg A, Cohen M, Shibolet O, Sklan E, Braspenning J, Nahmias Y. Long-term culture and expansion of primary human hepatocytes. Nat Biotechnol. 33:1264-1271. 

2014
Hanin G, Shenhar-Tsarfaty S, Yayon N, Yau YH, Bennett ER, Sklan EH, Rao DC, Rankinen T, Bouchard C, Geifman-Shochat S, Shifman S, Greenberg DS, Soreq H. Competing targets of microRNA-608 affect anxiety and hypertension. Hum Mol Genet. 23(17):4569-80.

2013
Stern O, Hung Y, Valdau O, Yaffe Y, Harris E, Hoffmann S, Willbold D, Sklan EH. An N-terminal amphipathic helix in the Dengue virus nonstructural protein 4A mediates oligomerization and is essential for replication. J. Virol. 87(7) 4080-4085. 

2012
Shlomai A, Rechtman MM, Burdelova EO, Zilberberg A, Hoffman S, Solar I, Fishman S, Halpern Z, Sklan EH. The metabolic regulator PGC-1α links hepatitis C virus infection to hepatic insulin resistance. J Hepatol. 57(4):867-73.

Nevo-Yassaf I, Yaffe Y, Asher M, Ravid O, Eizenberg S, Henis YI, Nahmias Y, Hirschberg K, Sklan EH. Role for TBC1D20 and Rab1 in hepatitis C virus replication via interaction with lipid droplet-bound nonstructural protein 5A. J Virol. 86(12):6491-502. 

Nachmias D, Sklan EH, Ehrlich M, Bacharach E. Human immunodeficiency virus type 1 envelope proteins traffic toward virion assembly sites via a TBC1D20/Rab1-regulated pathway. Retrovirology. 9:7. 

2011
Lee C, Ma H, Hang JQ, Leveque V, Sklan EH, Elazar M, Klumpp K, Glenn JS. The hepatitis C virus NS5A inhibitor (BMS-790052) alters the subcellular localization of the NS5A non-structural viral protein. Virology. 2414(1):10-8.

 Matto M, Sklan EH, David N, Melamed-Book N, Casanova JE, Glenn JS, Aroeti B. Role for ADP ribosylation factor 1 in the regulation of hepatitis C virus replication. J Virol. 85(2):946-5.

2010
Parameswaran P, Sklan E, Wilkins C, Burgon T, Samuel MA, Lu R, Ansel KM, Heissmeyer V, Einav S, Jackson W, Doukas T, Paranjape S, Polacek C, dos Santos FB, Jalili R, Babrzadeh F, Gharizadeh B, Grimm D, Kay M, Koike S, Sarnow P, Ronaghi M, Ding SW, Harris E, Chow M, Diamond MS, Kirkegaard K, Glenn JS, Fire AZ. Six RNA viruses and forty-one hosts: viral small RNAs and modulation of small RNA repertoires in vertebrate and invertebrate systems. PLoS Pathog. 6(2):e1000764. 

2008
Einav S, Gerber D, Bryson PD, Sklan EH, Elazar M, Maerkl SJ, Glenn JS, Quake SR. Discovery of a hepatitis C target and its pharmacological inhibitors by microfluidic affinity analysis. Nat Biotechnol. 26(9):1019-27. 

Mor I, Sklan EH, Podoly E, Pick M, Kirschner M, Yogev L, Bar-Sheshet Itach S, Schreiber L, Geyer B, Mor T, Grisaru D, Soreq H. Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility. J Cell Mol Med. 12(2):479-95.

Einav S, Sklan EH, Moon HM, Gehrig E, Liu P, Hao Y, Lowe AW, Glenn JS. The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection. Hepatology. 47(3):827-35. 

2007
Sklan EH, Serrano RL, Einav S, Pfeffer SR, Lambright DG, Glenn JS. TBC1D20 is a Rab1 GTPase-activating protein that mediates hepatitis C virus replication. J Biol Chem. 2282(50):36354-61. 

Sklan EH, Staschke K, Oakes TM, Elazar M, Winters M, Aroeti B, Danieli T, Glenn JS. A Rab-GAP TBC domain protein binds hepatitis C virus NS5A and mediates viral replication. J Virol. 81(20):11096-105. 

Perry C, Pick M, Podoly E, Gilboa-Geffen A, Zimmerman G, Sklan EH, Ben-Shaul Y, Diamant S, Soreq H. Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia. Leukemia. 21(7):1472-80. 

2006
Sklan EH, Berson A, Birikh KR, Gutnick A, Shahar O, Shoham S, Soreq H. Acetylcholinesterase modulates stress-induced motor responses through catalytic and noncatalytic properties. Biol Psychiatry. ;60(7):741-51.

Grisaru D, Pick M, Perry C, Sklan EH, Almog R, Goldberg I, Naparstek E, Lessing JB, Soreq H, Deutsch V. Hydrolytic and nonenzymatic functions of acetylcholinesterase comodulate hemopoietic stress responses. J Immunol. 176(1):27-35. 

2005
Rees TM, Berson A, Sklan EH, Younkin L, Younkin S, Brimijoin S, Soreq H. Memory deficits correlating with acetylcholinesterase splice shift and amyloid burden in doubly transgenic mice. Curr Alzheimer Res. 2(3):291-300. 

2004
Perry C, Sklan EH, Soreq H. CREB regulates AChE-R-induced proliferation of human glioblastoma cells. Neoplasia. 2004 May-Jun;6(3):279-86.

Sklan EH, Lowenthal A, Korner M, Ritov Y, Landers DM, Rankinen T, Bouchard C, Leon AS, Rice T, Rao DC, Wilmore JH, Skinner JS, Soreq H. Acetylcholinesterase/paraoxonase genotype and expression predict anxiety scores in Health, Risk Factors, Exercise Training, and Genetics study. Proc Natl Acad Sci U S A. 101(15):5512-7.

Nijholt I, Farchi N, Kye M, Sklan EH, Shoham S, Verbeure B, Owen D, Hochner B, Spiess J, Soreq H, Blank T. Stress-induced alternative splicing of acetylcholinesterase results in enhanced fear memory and long-term potentiation. Mol Psychiatry.9(2):174-83. 

2002
Birikh KR, Sklan EH, Shoham S, Soreq H. Interaction of "readthrough" acetylcholinesterase with RACK1 and PKCbeta II correlates with intensified fear-induced conflict behavior. Proc Natl Acad Sci U S A. 100(1):283-8.

Perry C, Sklan EH, Birikh K, Shapira M, Trejo L, Eldor A, Soreq H. Complex regulation of acetylcholinesterase gene expression in human brain tumors. Oncogene. 21(55):8428-41. PubMed PMID: 12466963.

2000
Sklan EH, Gazit A, Priel E. Inhibition of murine AIDS (MAIDS) development in C57BL/6J mice by tyrphostin AG-1387. Virology. 278(1):95-102.

Reviews
Sklan EH, Podoly E, Soreq H. RACK1 has the nerve to act: Structure meets function in the nervous system. Prog Neurobiol. 78 (2):117-34. 

Sklan EH, Glenn JS. The Power of silence: application of small interfering RNAs to gastrointestinal diseases. Gastroenterology. 132(7):2291-5. 

Sklan EH, Charuworn P, Pang PS, Glenn JS.Mechanisms of HCV survival in the host. Nat Reviews Gastroenterol Hepatol. 6, 217–22.

Books and Book chapters

Sklan EH., Shoham S. and Soreq H. (2004) Interaction of “Readthrough” Acetylcholinesterase with the PKC Scaffold Protein RACK1 Facilitates Antisense-Suppressible Contextual Fear Responses. In: "Cholinesterases in the Second Millennium: Molecular and Pathological Aspects" (N.C. Inestrosa and E.O. Campos, eds.), P. Univ. Católica de Chile, Santiago, Chile, pp 65-74

Shoham, S. Kovalev, E. Sklan, EH. and Soreq, H. (2004) Readthrough acetylcholinesterase and cholinergic transmission. In: Silman, I., Fisher, A., Anglister, L. Michaelson, D. and Soreq, H. (eds.) Cholinergic Mechanisms, Martin Dunitz, London.

Sklan, EH. Birikh, K. and Soreq H. (2004) Two hybrid approach to the intracellular function of readthrough acetylcholinesterase. In: Silman, I., Fisher, A., Anglister, L. Michaelson, D. and Soreq, H. (eds.) Cholinergic Mechanisms, Martin Dunitz, London.

Sklan EH, Glenn JS. (2006) The HCV non-structural protein NS4B: from obscurity to central stage. In Tan, S (ed.) Hepatitis C Viruses: Genomes and Molecular Biology, Horizon Bioscience, Norwich, UK, pp 245-266.

Sklan EH, Soreq H. (2009) Cholinergic stress and anxiety signal involve alternative splicing. VDM Verlag Dr. Müller Aktiengesellschaft & Co. KG, Saarbrucken, Germany. ISBN 978.

Contact us

Address:

Department of Clinical Microbiology and Immunology
Sackler Faculty of Medicine Room 805
Tel Aviv UNiversity

Phone:

+972-3-6409486
+972-3-6408197

E-mail:

sklan@tauex.tau.ac.il