1-The development of analytical methods to measure levels of NO(NOx)and H2S.
2- Picking out the specific amino acids within the proteins that are susceptible to S-nitrosylation and S-sulfhydration.
3- Identifying specific S-nitrosylated- and S-sufhydrated-proteins that are pivotal control points in a given pathology. A good example, of this is our recent work on the cell membrane-resident enzyme neutral sphingomyelinase (NSMase). When normal cells are exposed to stress (such as chemotherapeutic drugs), NSMase is stabilized and activated making more of a compound (creamide) causes the cells to self destruct (apoptosis). However, as we recently discovered, cancer cells when stressed inactivate NSMase by S-nitrosylating it thereby avoiding the self destruct-signal and surviving the stress. Currently, we are using our analytical/proteomic methods to indentify NSMase’s -S-N=O-susceptible regions with a view of preventing the inactivation of NSMase in cancer cells, thereby rendering them more susceptible to killing by chemotherapeutics.
