Nathan W. Schmidt, PhD

Malaria is an infectious disease caused by Plasmodium species.  Noteworthy advancements have been made in the control and treatment of malaria over the last two decades, resulting in a considerable decline of malaria-related fatalities.  Sadly, in 2017 there were still around 500,000 deaths caused by Plasmodium infections, primarily children <5 years of age living in sub-Saharan Africa.

Humans become infected with Plasmodium following the bite of an infected mosquito resulting in the deposition of sporozoites into the dermal tissue.  Sporozoites migrate from the dermal tissue to the liver and initiate the asymptomatic liver stage of infection.  During the liver stage the parasite differentiates into merozoites within infected hepatocytes.  Once differentiation is complete merozoites are released into the blood where they establish cyclical infections of red blood cells through asexual reproduction.  The blood stage of infection is what causes the clinical symptoms known as malaria.  The severity of Plasmodium infection ranges from asymptomatic to severe malaria, yet the factors that determine disease severity remain poorly understood.  Importantly, many aspects of human malaria are similar in the murine model of malaria, allowing us to pursue questions that would otherwise not be feasible.

Research in Dr. Schmidt’s laboratory is interested in understanding the factors that influence the severity of malaria.  We are currently pursuing this through the following projects:

1. Research over the last decade has provided revolutionary insight into the influence of the gut microbiome on many facets of host physiology, including host immunity.  We made the intriguing observation that the composition of gut bacteria can greatly impact the severity of malaria in mice.  This observation has raised many fascinating questions that are currently being explored in the laboratory.  These include:

a) What are the specific bacteria and their metabolic products that impact parasite burden?
b) Do differential gut bacteria compositions impact the severity of malaria through direct effects on Plasmodium or indirectly through modulation of the host immune response to Plasmodium?
c) Does gut microbiota impact the severity of malaria in African children?
d) Can gut microbiota be modulated to prevent severe malaria?

Answering these questions has the potential to identify novel gut microbiota-based therapeutics to prevent children from dying from severe malaria.

2. The host immune system plays a vital role in the control and clearance of Plasmodium infections. In particular, the adaptive immune response produces antibodies that are necessary and sufficient to eliminate merozoites and infected red blood cells. Unlike many other infections that elicit long-lasting protective immunity against subsequent infections, Plasmodium infections stimulate weak immunological memory. We are interested in understanding how Plasmodium infections, in particular during severe malaria, modulate the host immune system to prevent the induction of robust memory. Similarly, Plasmodium infections have also been shown to increase susceptibility to bacterial co-infections resulting in a higher fatality rate. Yet, the factors by which Plasmodium impairs host immunity to bacterial co-infections are poorly understood. Collectively, the ability of Plasmodium to impede the host immune system contributes to the pathogenesis of this infectious disease.  Through addressing these knowledge gaps, we hope to identify methods of intervention that will decrease the pathogenesis of malaria.