Doron C. Greenbaum, Ph.D.

Description of Research Expertise

Research Interests

Dr. Greenbaum's laboratory is developing and exploiting new technologies at the interface between biology and chemistry to study protease function. The lab uses a variety of techniques including the synthesis of small molecule inhibitors, quantitative proteomics, recombinant protein expression and molecular genetics in order to better understand proteolytic systems. Although these tools are useful to study any biological system, the laboratory is concentrating on understanding host and parasite proteases that are important for P.falciparum, the causative agent of malaria.

Malaria is a devastating global disease causing at least 500 million clinical cases and more than 1 million deaths each year. Currently quinolines and anti-folates are the most commonly used drugs for disease prevention and treatment. However, multi-drug resistant Plasmodium falciparum has become a major problem. Therefore, discovery and investigation of known and/or novel targets for anti-malarial compounds is essential to develop new ways to combat this disease.

Dr. Greenbaum has developed universal chemical-based proteomics tools to functionally analyze the role of proteases in a variety of biological systems. He also adapted these chemical tools to allow screening of small molecule libraries for specific inhibitors and drug design. His lab will continue to develop new chemical proteomic tools and small molecule libraries to facilitate protease drug target discovery, characterization and therapeutic design with a particular interest in malaria.

The chemical probes that Dr. Greenbaum is developing led to the recent discovery that parasites such as plasmodium and toxoplasma hijack host calpains in order to facilitate their escape (Chandramonanadas et al, Science 324:794-7; 2009). This surprising finding suggests the concept of targeting host pathways for chemotherapy, a strategy that might limit the emergence of drug-resistance.