Comini Olmedo, Marcelo Alberto

Research interests

Fundamental aspects of trypanothione metabolism: synthesis, reduction and utilization
We study the biochemical, structural and biological features that distinguish several key components of the trypanothione system from pathogenic trypanosomatids. Using animal infection models, we investigate the role these molecules play in parasite biology and pathogenesis. The data from these studies allows to validate new drug target candidates, their inhibitors as well as to guide novel drug development strategies.

Development of biosensors for non-invasive and high-content studies
Our laboratory is interested in the development of different types of biosensors (fluorescence- and luminescence-based) that allow the real time and non-invasive monitoring of parasite proliferation, redox state and major signaling pathways. The transgenic cell lines expressing the biosensors allow us to study the role played by the oxidative stress and redox signaling in a variety of cellular processes (e.g. host-pathogen interaction, cell differentiation, cell cycle, apoptosis and metabolic dysfunction). The reporter cell lines are also used in phenotypic drug-screening campaigns and to investigate drug mode of action.

Early phase drug discovery projects
We apply target- and phenotypic-based approaches to screen synthetic and natural compounds that affect, in a selective manner, the growth of the infective form of different trypanosomatid species.
Drug repurposing is also an active area of research in our lab. Drug mode of action at cellular and enzymatic level is addressed to foster and guide drug optimization. Our laboratory relies on an important network of local and international groups working on (medicinal) chemistry to fulfill this goal.

Working area

By means of a multidisciplinary approach, we study the biochemical, structural and biological features that distinguish several key components of the redox system from pathogenic trypanosomatids, parasites that are causative agents of severe diseases in animals and humans (Chagas disease, Leishmaniasis and African sleeping sickness).
These studies allow us to identify and understand the role these components play in parasite biology (e.g. growth, infection, and pathogenesis).
Our research aims to gain understanding into the redox biology of trypanosomatids to guide novel strategies and the development of the safer and more efficacious drugs against this disease.