Associate Professor, Department of Microbiology & Immunology
Associate Professor, Department of Medicine (Infectious Diseases)
My interest in what is now being termed global health started in medical school. I spent a two month elective at Kenyatta National Hospital in Nairobi joining the pediatric in patient team. Malaria was a major problem. During my Internal Medicine Residency I spent two months at the London School of Tropical Medicine and Hygiene and observed both in-patients and outpatients with tropical diseases and sat in on research conferences. These experiences informed me sufficiently to choose Infectious Disease as a subspecialty with laboratory training in the molecular biology of Plasmodium in Dyann Wirth’s lab at HSPH. We carried out drug resistance studies in Senegal and I began my work looking at the diversity of parasite gene expression as measured directly from patient blood (no interim culture). We discovered novel biological states.
My other efforts were in outcomes research working with Paul Farmer and the Global Health and Social Inequities Division at BWH. Our goal was to utilize a routinely measured outcome such as pediatric hospitalizations to measure impact of a multipronged antimalarial campaign. Finally I have been interested in the utilization of UpToDate in resource limited settings. We deployed this evidence based medical resource in a number of health care facilities and are now measuring its impact. I am interested in both basic science and outcomes research in malaria.
Our primary research interest is in 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 study the parasite under in vitro conditions that mimic host blood stream conditions. We are also studying host response to infection using whole genome approaches to identify host factors that associate with severe disease outcomes. To complement these approaches we have started to analyze small molecules generated from the parasite to further characterize its’ biology and potentially identify biomarkers. The long term goal is to identify parasite and host processes involved in disease to serve as targets for vaccine or chemotherapeutic development. 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.
Students are most welcome to join in the work that explores basic epidemiology and parasite transcription and host factors that impact this biology. We carry out basic science efforts in the analysis of parasite and host whole genome transcriptional data through a collaboration with Terrie Taylor's (Michigan State) group in Blantyre, Malawi in children with severe disease; with Kathy Anastos (Einstein) in malaria infected adults with and without HIV in Rwanda. We are beginning to explore plasma, urine and saliva for small molecule signatures of parasites and biomarker development. Finally in collaboration with Carol Harris (Einstein) we are carrying out basic epidemiology and outcomes research of malaria in Ethiopia.