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Researchers
  • Prof.  Ariella Oppenheim
Prof Ariella Oppenheim
 
Research Interest
Our research interest is to understand cellular processes at the molecular level. We use the non-pathogenic virus SV40 to probe cellular processes and mechanisms. In addition we explore the possibility to utilize the knowledge for medical applications. SV40 is a small virus with a double stranded DNA genome. It has served for many years as a paradigm for studies on eukaryotic DNA replication, transcription and RNA processing.
 
Virus-induced cellular signaling
Upon infection SV40 elicits multiple signaling in the host, which facilitate its endocytosis, cellular trafficking, and propagation cycle. We specifically focus on signaling induced by the viral capsid proteins prior to nuclear entry and viral gene expression. We found that upon infection SV40 elicits complex signaling networks, including pro-apoptotic signaling and survival pathway. Intriguingly these two opposing pathways are robustly balanced, as the cells neither apoptose nor proliferate. Regulation of this balance is presently a major interest.  Under investigation.

Our basic research leads to medical applications
Medical applications stem from basic research
Survival pathway and other signaling cascades induced by recombinant empty capsids lead to protection against Acute Kidney Injury (AKI) in mouse and rat preclinical models. As these pathways are common to other organs, the same strategy may be applicable to a range of clinical conditions. Development of such medical applications is underway.

The tumor suppressor p53 functions in viral host defense by modulating viral transcription.
We found that p53 is activated in SV40-infected cells as part of the host defense response. p53 commonly functions in host defense by leading infected cells towards apoptosis. However, in the case of SV40, p53 aborts the infection by repressing T-antigen expression. This system provides a unique and simple experimental model to investigate the molecular basis of p53 tumor suppression activity.

Nuclear entry of the infecting virus
The infecting virus activates caspase-6 and 10 by an unknown mechanism. This novel caspase pathway leads to dramatic deformation of the nuclear envelope, which facilitates nuclear entry of viral genome. We plan to use this experimental system to study the structure of the nuclear envelope and the mechanism that protects its integrity.

Basic laws that govern protein assemblages
Cellular proteins commonly function in assemblages, such as transcription complex, replication complex or signaling complexes. Some of these complexes are transient and some more stable. We investigate SV40 capsid assembly in vitro as a model for the formation of such assemblages. Our interest is in protein-protein and protein-nucleic acids interactions that lead to assembly, and in forces that keep the assembled particles together.
 
 
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Relevant recent publications
Stanislav Kler, Joseph Che-Yen Wang, Mary Dhason, Ariella Oppenheim and Adam Zlotnick. 2013. Scaffold properties are a key determinant of the size and shape of self-assembled virus-derived particles. ACS chemical biology 8, 2753-2761. Link
 
Drayman, N., Glick, Y., Ben-Nun-Shaul, O., Zer, H., Zlotnick, A., Gerber, D., Schueler-Furman, O., Oppenheim, A. 2013. Pathogens use structural mimicry of native host ligands as a mechanism for host receptor engagement. Cell Host Microbe 14: 63-73. Link
 
Gadiel Saper, Stanislav Kler, Roi Asor, Ariella Oppenheim, Uri Raviv and Daniel Harries. 2013. Effect of capsid confinement on the chromatin organization of the SV40 minichromosome. Nucleic Acids Research 41:1569-1580. Link
 
Oren Kobiler, Nir Drayman, Veronika Butin-Israeli and Ariella Oppenheim. 2012. Virus strategies for passing the nuclear envelope barrier. Nucleus 3:6, 1–14. Link
 
Kler, S., Asor, R., Li, C., Ginsburg, A., Harries, D., Oppenheim, A., Zlotnick, A., Raviv, U. 2012. RNA rapidly assembles SV40 VP1 pentamers into T=1 nanoparticles without appreciable intermediate concentrations. J. Am. Chem. Soc, 134, 8823−8830. Link
 
Veronika Butin-Israeli, Orly Ben-nun-Shaul, Idit Kopatz, Stephen A . Adam, Takeshi Shimi, Robert D Goldman and Ariella Oppenheim. 2011. Simian Virus 40 Induces Lamin A/C Fluctuations And Nuclear Envelope Deformation During Cell Entry. Nucleus, 2(4): 320-330. Link
 
Veronika Butin-Israeli, Nir Drayman and Ariella Oppenheim. 2010. Simian virus 40 infection triggers balanced network that includes apoptotic, survival and stress pathways. J. Virol. 84:3431-3442. Link
 
Orly Ben-nun-Shaul, Hagit Bronfeld, Dan Reshef, Ora Schueler-Furman, Ariella Oppenheim. (2009). The SV40 Capsid Is Stabilized by a Conserved Pentapeptide Hinge of the Major Capsid Protein VP1. J. Mol. Biol. 386, 1382–1391. Link
 
Veronika Butin-Israeli, Dotan Uzi, Mahmoud Abd-El-Latif, Galina Pizov, Aryeh Eden, Yosef S. Haviv,  and Ariella Oppenheim. 2008. DNA-free recombinant SV40 capsids protect mice from acute renal failure by inducing stress response, survival pathway and apoptotic arrest. PLoS ONE. Aug 20;3(8):e2998. Link
 
Luminita Eid, M.D., Zohar Bromberg, M.Sc., Mahmoud Abd EL-Latif, B.S., Evelyn Zeira, B.S, Ariella Oppenheim, Ph.D., Yoram G. Weiss, M.D. 2007. Simian Virus 40 Vectors for Pulmonary Gene Therapy. Respiratory Research, 8:74. Link 
 
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