Drug and drug target discovery for diseases caused by protozoan pathogens
Single-celled parasites cause devastating diseases in humans and non-human animals throughout the world. Despite the tremendous global burden, safe and effective drugs for many of these diseases are lacking. Our lab is dedicated to discovering new treatments for neglected protozoan diseases using molecular tools to identify new drug targets and medicinal chemistry to optimize small molecules for clinical use. We are specifically focused on the apicomplexan pathogens, Toxoplasma gondii, Plasmodium falciparum and Babesia.
Toxoplasmosis
More than one fourth of humans are estimated to be chronically infected with Toxoplasma gondii. In patients with intact immune systems, T. gondii infection may be asymptomatic or may cause an influenza-like illness, lymphadenopathy, or eye disease. In fact, T. gondii is a leading cause of posterior uveitis and a major cause of childhood blindness. In persons with AIDS or other immune deficiencies, initial infection or reactivation of previous infection can cause severe brain, lung or eye disease. Developing fetuses can acquire infection during pregnancy, resulting in miscarriage or severe birth defects. Toxoplasmosis is also an important veterinary disease. Current treatments are limited by allergic reactions and hematologic toxicity.
Our research has identified and developed promising preclinical candidates for toxoplasmosis and we are currently exploring new drug targets for toxoplasmosis.
Toxoplasma gondii
Malaria
Each year, Plasmodium falciparum causes over 200 million cases of malaria and over 400,000 deaths. Most of these deaths occur in children under 5-years-old.
Global elimination of human malaria is possible, however, P. falciparum has developed resistance to all current antimalarial drugs. New drugs and treatment strategies to overcome resistance are urgently needed.
​
Our lab is focused on studying the mechanism of action of preclinical antimalarial compounds, understanding how chemical structure relates to efficacy, and discovering new strategies to overcome anti-malarial resistance.
Plasmodium falciparum
Babesiosis
Babesia divergens
Babesiosis is a blood infection primarily caused by Babesia microti, which occurs in the Northeastern and upper Midwestern United States, and is transmitted by Ixodes scapularis ticks. In Europe, most cases are attributable to B. divergens and sporadic cases with other Babesia species have been reported in Europe and worldwide. Disease severity ranges from asymptomatic to fatal. Immunocompromised patients may have relapsing infection that is refractory to treatment.
​
We have collaborated with others to discover an effective treatment for refractory babesiosis in a mouse model, which may ultimately be used in immunocompromised patients.