Dr. Efrat Shavit-Stein
Email: efrat.shavit.stein@gmail.com, Efrat.ShavitStein@sheba.health.gov.il
Phone: 03-5304409, 050-9210400
Position: Research Director
Education:
2004-2010, PhD, Neurosciences, Physiology, and Pharmacology, Tel Aviv University, Israel
2000-2003, B.SC, Medical and ife sciences, Tel Aviv University, Israel
Affiliations:
Department of Neurology and Neurosurgery, Faculty of Medicine, Tel Aviv University, Israel
Research Insterests:
The link between coagulation and complement proteins and the nervous system function in health and disease is a central research subject and interest for me. For decades, the coagulation cascade proteins were considered as blood-born proteins and only in recent years their local production role in the nervous system is being studied in detail. I am mainly interested in understanding the coagulation factors role in the glia and neuron function, interaction and regulation, as well as how they modify animal behavior and function. We have focused our attention on the role of a central coagulation factor thrombin, and the protease activated receptors (PARs) that it activates in the nervous system.
We have mainly focused on PAR-1 as it is the most abundant subtype in the brain. We have examined the anatomical localization and physiology of PAR1 at both the synapse and the node of Ranvier. We have published a paper in which we have shown that PAR1 at the synapse is located predominantly on the glial astrocytic endfoot, and that activation of the receptor causes synaptic depolarization.
In a collaborative study we found that stimulation of PAR1 with excessive levels of thrombin induces long term potentiation and epileptic seizures. In a very important work that was published in the journal “Brain”, we described that PAR1 is located on the glial perinodal endfoot at the node of Ranvier. Activation of the receptor produces a profound inhibitory effect at the nodes resulting in conduction block. This is the first demonstration of a physiological role for this glial structure at the node.
We have further studied the thrombin-PAR1 pathway in animal models for neuropathy: the streptozotocin (STZ) model for diabetic peripheral neuropathy, and the experimental autoimmune neuritis (EAN) as a model for inflammatory demyelinating neuropathy. We have found that thrombin-PAR1 pathway in the peripheral nerve itself plays a central role in the nerve dysfunction and neuropathy process in both models. Specific thrombin inhibition mediates a beneficial effect on nerve conduction.
Commercial thrombin inhibitor drugs are in clinical use for several indications, but due to their effect on systemic thrombin, there is a major risk for bleeding, which limits their use. We have developed new molecules that specifically target the PAR1/thrombin pathway as well as the aPC/EPCR/PAR1 pathway and spare the systemic coagulation side effects as bleeding. We found and published their beneficial effects in several studied models such as diabetic neuropathy, GBM, diabetic retinopathy, and systemic and local inflammation.
Research Grants & Awards:
2023, Characterization Of the Neuro-Glial Coagulonome in Peripheral Nerves and Its Modulation to Treat Polyneuropathy, ISF
2023, Charracterization of Complement Components in the Physiology and Pathology of the Optic Nerve, The Martier Institute for the Study of the Blindness& Visual Disorders
2023, Innovative eye drops formulation for treatment of Diabetic Retinopathy, “Nofar” Israel Innovation Authority
2021, CBD in Treating Epilepsy, SciSparc
2021, Biomarkers of transthyretin amyloid polyneuropathy, Pfizer
2020-2023, A novel diagnostic tool in ischemic stroke, Israel Ministry of Economy- Kamin
2016-2018, Novel molecules for the treatment of neuroinflammation, Israel Ministry of Economy- Kamin
2014-2017, Novel compounds for the treatment of GBM and Neuropathy, Israel Ministry of Economy- Kamin
Honirs, Awards, Prizes:
2021, TELEM Excellence Research Program in Sheba Medical Center
2021, Excellent teacher at Tel-Aviv University Medical School
2019, Excellent researcher in the laboratory department, Sheba Medical Center
2018, The original and excellent abstract of the annual neurological conference
2005-2010, The Sagol scholarship for excellence in brain research
Publications:
Here is a link to the publications of Dr. Efrat Shavit-Stein
Here you can find her publications at scopus
