The lab is jointly run by Professor Michael Pollastri and Professor Lori Ferrins. With a background in synthetic organic and industrial medicinal chemistry, and chemical technology, our research program focuses on those areas of research that will impact on treatment of human disease, and on areas that will expedite the drug discovery process. As an industrialized outpost of medicinal chemistry in academia, we use state-of-the-art computational and database tools for compound design and data analyses, cutting-edge synthesis, and purification approaches, all combined with creative organic and medicinal chemistry. There are several themes to our research, which are broadly contained under the umbrella of infectious diseases.
Neglected Tropical Diseases and Parasitic Infections
Neglected tropical diseases are those that do not attract sizable research investment in the private sector since these diseases affect the poorest parts of the world. Since there is little potential to recoup the research and development costs (let alone make a profit), pharmaceutical companies do not typically marshal research programs of great significance against these diseases. Therefore, this represents a major opportunity for public sector, not-for-profit entities (such as academic institutions) to play a major role in developing new therapies for neglected diseases.
The main thrust of our program is to identify biological targets in pathogenic parasites that are homologous to biological targets in humans that have been pursued for drug discovery efforts in the past. We then repurpose these historical drug discovery efforts (compounds, structural information, general knowledge) for discovering new leads that can be optimized for activity against the parasite. Due to the presence and importance of kinases and phosphodiesterases in protozoan parasites such as Trypanosoma brucei, Trypanosoma cruzi, Leishmania sp., and Plasmodium falciparum, we are focused primarily on repurposing inhibitors that target these druggable enzyme families. Recently, we have incorporated structure-based drug discovery into our programs and are using this information to drive optimization efforts.
The World Health Organization named infections due to Candida albicans and C. auris to their fungal priority pathogen list as requiring critical attention, additionally, C. tropicalis, C. glabrata and C. parapsilosis were also recognized as high-priority fungal infections. Dr. Julia Koehler at Boston Children’s Hospital recently developed a high-throughput screen to look for inhibitors of three Candida targets. These targets do not have human orthologs, nor do the compounds need to enter the fungus to have their effect which is one of the main drivers of resistance. This work has yielded multiple chemotypes of interest that have entered hit-to-lead optimization.
Amoebae lead to a range of brain, skin, eye, and disseminated diseases in humans and animals which are typically fatal. Due to the high mortality rate, poor therapeutic options, and lack of awareness and detection, Acanthamebiasis is classified as a category C NIAID additional emerging infectious disease. The recommended treatments are empirically based on reports of a very limited number of survivors, with no current FDA-approved drugs for use. Pathogenic free-living amoeba are the epitome of the neglected emerging infections, with no major drug discovery efforts conducted by pharmaceutical companies or academic labs. With Dr. Chris Rice from Purdue University, we are working to develop a program that leverages target-based drug discovery, coupled with phenotypic drug discovery. We believe that target engagement information, in conjunction with phenotypic data and secondary assays provides us with the best chance at developing therapeutics.