Redox Regulation, Inflammation, and Cancer

Moran Benhar, Ph.D.

Moran BenharDepartment of Biochemistry | Faculty of Medicine


Rappaport Building, 6th floor
Tel: +972-4-829-5376
Fax: +972-4-829-5412


פרופסור מורן בנהר – מחלקה לביוכימיה


Protein functionality is often dependent on post-translational modifications, such as phosphorylation and ubiquitination. Accumulating evidence suggests that protein cysteine oxidation serves important roles in many aspects of cellular function, including cell growth, differentiation, and death. However, there is still limited understanding of the scope and significance of the cysteine redox proteome in different cell types and under different cellular states.

The main goal of our lab is to understand how redox modifications of cysteine residues regulate protein and cell function.

Cysteines confer redox regulation of protein function, namely the reversible post-translational modification that alters protein activity as a result of change in its oxidation state.  In response to changes in cellular levels of reactive oxygen and nitrogen species (ROS and RNS) cysteine thiol (-SH) groups undergo a spectrum of covalent modifications, including nitrosylation, sulfenylation, and disulfide formation. These reversible thiol modifications are increasingly recognized to regulate a wide range of cellular functions, such as proliferation, migration, differentiation, and death.


Fig hhiol switches


Modification of a protein cysteine thiol by reactive nitrogen/oxygen species such as nitric oxide (NO) or hydrogen peroxide (H2O2) leading to nitrosylation (SNO) or sulfenylation (SOH). Additional cysteine modifications are shown below.





We are particularly interested in redox regulation through S-nitrosylation, the attachment of NO moiety to cysteine thiol.  Our research team is studying the role of S-nitrosylation in cellular signaling, inflammation and cancer. We employ global (proteomics) as well as more directed and targeted approaches to discover novel nitrosylation-based control mechanisms.


SNO caspase3

Structural model of S-nitrosylated caspase-3.  Binding of the nitric oxide group (red color) to the active site cysteine inhibits caspase activity resulting in protection from programmed cell death (apoptosis).







In addition to nitric oxide, the gaseous molecule hydrogen sulfide (H2S) as recently emerged has a novel signaling molecule the affects diverse cellular processes.  Cellular effects of H2S are mediated in part via cysteine persulfidation (Cys-SSH).


Our research goals are:

1. Identify novel targets of NO and H2S in macrophages and cancer cells

2. Elucidate how H2S regulates cancer cell death

3. Develop new proteomic methods to analyze protein S-nitrosylation.

4.  Characterizate of the thiol redox proteome in the macrophage inflammatory response.

5. Elucidate the role of antioxidant systems in regulating protein nitrosylation and persulfidation