Research Areas:
The research in
our lab is focused in translational research. In the past we focused mainly in studying
HCV infection, viral host interaction with attempt todevelop inhibitors active against a broad range of HCV genetic variants. In the last few years we expand our interest
to the field of solid organ transplantation and immunology of rejection. In
both research fields, we apply cutting-edge technologies including viral
infection, CRISPR cas9 gene editing, exosomes purification, as well as immunological,
molecular, protein and cellular biology methods.
Molecular Hepatology
Vitamin-D- an innate antiviral agent
suppressing Hepatitis C virus in human hepatocytes.
Vitamin D3remarkably inhibit hepatitis C virus production. This
anti-hepatitis C virus activity is mediated by vitamin D primary
metabolic product 25(OH)D3 in a VDR independent mechanism. A. Inhibition
of hepatitis C virus production determined by HCV infectious assay (a. HCV b. HCV+
Vitamin D). B. vitamin D metabolism and action. C. 25(OH)D3 dose
dependent inhibition. D. Inhibition of HCV
in CRISPR-Cas9 VDR-KO cells clones (#2 and #6(.
Electron microscopy analysis of HCV infected (a) and non-infected (b) cells for
studying the effect on cell morphology.
We are now pursuing
our research further to explore the mechanism by which vitamin D metabolite
exert its inhibitory effect on Hepatitis C.
Transplantation Immunology
·
Tissue
engineering to diminish alloimmunity in organ transplantation
Decreased NK cells cytotoxicity to HEK293-MICA-KO target cells. We
used the CRISPR/Cas9 editing system to knockout the NKG2D stress induced
ligands. Loss of MICA gene product in the knockout cells compared to the WT
cells, sequence analysis shows a mixture of sequences in the KO cells compared
to the WT cells (B) and Flow cytometry analysis shows a decreased expression of
MICA (C). Knocking down MICA, results in 35-50% reduction in NK cells
cytotoxicity (analyzed by cell killing assays)(D).
• Effect of immunosuppressive drugs on
NK cells activation.
In this study, we use immunological, molecular biology and protein
analysis to test the effect of commonly used clinical immunosuppressive drugs
on NK cell activity in in-vitro tissue culture system. Taking advantage of
being part of the department of organ transplantation, that performs most
of the organ transplants in Israel, we plan to study this effect on human
transplanted patients.
• Urinary Exosomes as Biomarkers and
Therapeutic Targets in Polyomavirus-Associated Nephropathy
In collaboration with Dr. M. Herman-Edelstein and Dr. N. Ben-Dor
This
study combines basic virology with clinical practice to study BK
virus -associated nephropathy following transplantation, and to evaluate the
potential use of urine exosomes as a novel and non-invasive biomarker for BK
reactivation.