Our primary research interest is in the biology, pathogenesis and drug resistance in the malaria parasite Plasmodium falciparum. Patients infected with this parasite can be completely asymptomatic or develop severe disease resulting in death. The goal of our research has been to define the molecular mechanisms that underlie this variation in disease outcomes in P. falciparum. Toward this goal, we have developed a new pathogenesis model through the analysis of in vivo parasite biology and associated host factors using a whole genome approach. We have identified novel parasite biology when it resides in the human host; this biology has not been reported under in vitro cultivation and may play a role in enhanced virulence and/or transmission capacity. To further understand the implications of these novel in vivo states we will study the parasite under in vitro conditions that mimic host blood stream conditions. We have also identified distinct host states associated with clinical disease phenotypes. This may suggest that the host context modulates infection outcome. The long term goal is to identify parasite and host processes involved in disease to serve as targets for vaccine or chemotherapeutic development. In addition we have begun to identify parasite specific small molecules to study its biology using a complementary approach and potentially these molecules could serve as biomarkers of infection. We carry out field based translational studies in cohorts infected with malaria in Africa and these inform our experimental work using basic molecular biology approaches in the laboratory.