Page 15 - Rappaport Institute Magazine 2024

BIOCHEMISTRY
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Redox Regulation, Inflammation, and Cancer
Our research group studies how oxidant and antioxidant systems regulate cellular processes involved in inflammation and cancer. In particular, we investigate the regulation of protein and cell function by the gaseous signaling molecules nitric oxide (NO) and hydrogen sulfide (H2S) and by the cellular antioxidant systems. The laboratory combines comprehensive and targeted approaches to study NO/H2S-dependent redox modifications of proteins. More broadly, the laboratory goal is to gain a mechanistic understanding as to how redox systems (oxidants/antioxidants) regulate normal cellular physiology and how their dysregulation contributes to human disease, particularly cancer. Our current research efforts are aimed to elucidate redox mechanisms that regulate inflammatory processes in macrophages and apoptotic and non-apoptotic cell death in cancer cells.
Selected Publications
ˆ Braunstein, I., Engelman, R., Yitzhaki, O., Ziv, T., Galardon, E. and Benhar, M. Opposing effects of polysulfides and thioredoxin on apoptosis through caspase persulfidation. J. Biol. Chem. 295:3590-3600, 2020.
ˆ Knany, A., Engelman, R., Abu Hariri, H., Biswal, S., Wolfenson, H. and Benhar, M. S-nitrosocysteine and glutathione depletion synergize to
induce cell death in human tumor cells: insights into the redox and cytotoxic mechanisms. Free Radic. Biol. Med. 160:566-574, 2020.
ˆ Abu Hariri, H., Braunstein, I., Salti, T., Glaser, F., Gefen, T., Geva-Zatorsky, N., Ziv, T. and Benhar, M. Global thiol proteome analysis provides novel insights into the macrophage inflammatory response and its regulation by the thioredoxin system. Antioxid. Redox Signal. 38(4-6):388, 2023.
Grants and Awards
2019 – 2023, Israel Science Foundation
2021 – 2024, DFG German Research Foundation, Co-PI: Ulrich Schaible € (Research Center Borstel, Germany).
2022 – 2026, The U.S.-Israel Binational Science Foundation (BSF),
Co - Principal Investigator: Prof. Huiwang Ai (University of Virginia, USA)
benhar@technion.ac.il
Moran Benhar Lab
Moran Benhar, PhD Associate Professor of Cell Biology
PhD, 2002 – The Hebrew University of Jerusalem, Israel
Generation of reactive oxygen/nitrogen/sulfur species (ROS/RNS/RSS) leads to modifications of protein cysteine thiols (R–SH) to various oxidized forms, such as R–SOH, R–SNO, and R–SSH, thereby altering protein functionality. Glutathione (GSH) and thioredoxin (Trx) govern the redox state of proteins by preventing of reversing these modifications.