Dr. Anthony O’Donoghue, Ph.D.

Our research is focused on the detection and characterization of proteolytic enzymes associated with disease.   Many of the proteases that we study are found in infectious organisms, cancerous tissues, immune cells or human biofluids.  Following in depth characterization of the target proteases, we develop potent and selective inhibitors to inactivate these enzymes or fluorogenic substrates to monitor catalytic activity.  

We use a platform technology called Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS) to uncover the global proteolytic activity in complex biological samples and have successfully applied it to blood, pancreatic cyst fluid, gastric juice of cancer cells and microbiobes. Our workflow also includes proteomic and peptidomics analysis to identify the proteases and endogenous substrates in the biological sample. Knowledge of which proteases are functionally active in diseased tissue and not active in healthy tissue allow us to 1) develop inhibitors to inactivate the target enzyme, 2) generate protease-activated imaging agents to locate the disease or 3) develop protease- activated drugs to aid in the delivery of toxic compounds to the site of disease.  Our group is highly collaborative and we routinely generate substrate specificity profiles of endo proteases, aminopeptidases or carboxypeptidases that have been isolated from diverse life forms such as bacteria, fungi, viruses, plants, protozoa, mammals  ticks, crustaceans and nematodes.