12491-Schmidt, Nathan
Faculty

Nathan W. Schmidt, PhD

Associate Professor of Pediatrics

Bio

Nathan Schmidt, PhD, received a BS in Biology from Olivet Nazarene University in 2001 and a PhD in Microbiology and Immunology from Indiana University in 2005.  He did postdoctoral work at the University of Iowa. Dr. Schmidt joined the faculty in the University of Tennessee in 2011 and then the faculty in the University of Louisville in 2014. In 2019, Dr. Schmidt was recruited to the faculty in Indiana University School of Medicine as an Associate Professor in the Department of Pediatrics and a member of Ryan White Center for Pediatric Infectious Diseases and Global Health.  

 

Dr. Schmidt’s research is focused on malaria, which is a parasitic disease caused by infection with Plasmodium species. Dr. Schmidt is interested in defining the factors that impact the pathogenesis of this disease and identifying novel approaches to prevent children from dying from malaria. One of the observations made by Dr. Schmidt’s research program was that the composition of bacteria residing within the intestinal tract can profoundly impact the severity of malaria. The influence of gut microbiota on malaria remains a central focus of his research interests.

Key Publications

White CE, Villarino NF, Sloan SS, Ganusov VV, and Schmidt NW.  Plasmodium suppresses expansion of T cell responses to heterologous infections.  The Journal of Immunology, 2015, 194:697-708.

Villarino NF, LeCleir GR, Denny JE, Dearth SP, Harding CL, Sloan SS, Gribble JL, Campagna SR, Wilhelm SW and Schmidt NW.  Composition of the gut microbiota modulates the severity of malaria.  Proceedings of the National Academy of Sciences, 2016, 113:2235-2240.

Ippolito MM, Denny JE, Langelier C, Sears CL, and Schmidt NW. Malaria and the microbiome: a systematic review. Clinical Infectious Diseases, 2018, 67:1831.

Denny JE, Powers JB, Castro HF, Zhang J, Joshi-Barve S, Campagna SR, and Schmidt NW. Severity of Plasmodium infection in mice differentially affects gut-liver axis homeostasis. Scientific Reports, 2019, 9:3472.

Mandal RK, Crane RJ, Berkley JA, Gumbi W, Wambua J, Ngoi JM, Ndungu FM, and Schmidt NW. Longitudinal analysis of infant stool bacteria communities before and after acute febrile malaria and artemether/lumefantrine treatment. The Journal of Infectious Diseases, 2018, doi: 10.1093/infdis/jiy740.

Titles & Appointments

  • Associate Professor of Pediatrics
  • Adjunct Associate Professor of Microbiology & Immunology
  • Education
    2005 PhD Indiana University
    2001 BS Olivet Nazarene College
  • Research

    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.

  • Awards
    Org: American Society of Tropical Medicine and Hygiene
    Desc: Scientific Excellence in Molecular, Cellular, and Immunoparasitology
    Scope: International
    Date: 2017-11-06
    Org: American Cancer Society
    Desc: Research Scholar Award
    Scope: National
    Date: 2014-07-01

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