Nathan Schmidt, Ph.D.

Nathan Schmidt, Ph.D.

Students:

Joshua Denny

Chris Harding

Morgan Duff

Postdoctoral fellow:

Rabindra Mandal 

Research Interests

Infection with Plasmodium, which is the parasite responsible for malaria, is a global health crisis.  Approximately 50% of the world's population lives in malaria-endemic regions and about 1 million people die from malaria annually.  Plasmodium infections are initiated when an infected mosquito takes a blood meal and deposits sporozoites into the dermal tissue, which migrate to the liver and initiate the asymptomatic liver stage of infection.  During the liver stage the parasite differentiates into merozoites that are released from the liver and establish cyclical infections of red blood cells through asexual reproduction during the blood stage.  It is the blood stage of infection that causes pathology associated with Plasmodium infections.  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 immunological and environmental factors that contribute to the pathology of malaria.  We are currently pursuing this through the following projects.

One of the complications with malaria is susceptibility to coinfection with other bacteria and viruses.  Consequently, we are interested in defining how Plasmodium impairs host innate and adaptive immunity to other pathogens.

The severity of Plasmodium infections range from asymptomatic to severe malaria, yet the factors that determine disease severity are poorly understood.  The composition of the gut microbiome is known to modulate many facets of host physiology including host immunity.  Therefore, we are pursuing how the gut microbiome shapes susceptibility to severe malaria.

Select Publications

Schmidt NW, Podyminogin RL, Butler NS, Badovinac VP, Tucker BJ, Bahjat KS, Lauer P, Reyes-Sandoval A, Hutchings CL, Moore AC, Gilbert SC, Hill AV, Bartholomay LC, and Harty JT. Memory CD8 T cell responses exceeding a large, but definable threshold provide long-term immunity to malaria.  Proceedings of the National Academy of Sciences, 2008, 105:14017-14022.

*Schmidt NW, *Butler NS, Badovinac VP, and Harty JT. Extreme CD8 T cell requirements for anti-malarial liver-stage immunity following immunization with radiation attenuated sporozoites.  PLoS Pathogens, 2010, 6:e1000998.  *Authors contributed equally.

Schmidt NW and Harty JT. Cutting Edge: Attrition of Plasmodium-Specific Memory CD8 T Cells Results in Decreased Protection That Is Rescued by Booster Immunization.  The Journal of Immunology, 2011, 186:3836-3840.

*Butler NS, *Schmidt NW, Vaughan AM, Aly AS, Kappe SH, and Harty JT.  Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites. Cell Host & Microbe, 2011, 9:451-462  *Authors contributed equally.

Villarino NF and Schmidt NW.  CD8+ T cell responses to Plasmodium and intracellular parasites.  Current Immunology Reviews, 2013, 9:169-178.

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

Villarino NF, Denny JE and Schmidt NW.  Antimalarial activity of tulathromycin in a murine model of malaria. Antimicrobial Agents and Chemotherapy, 2015, 59:3672-3674.

Villarino NF, LeCleir GR, Denny JE, Dearth SP, Sloan SS, 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.

 

Denny JE, Powell WL, and Schmidt NW. Local and long-distance calling: Conversations between the gut microbiota and intra- and extra-gastrointestinal tract infections.  Frontiers in Cellular and Infection Microbiology, 2016, 6:41.

 

Li B and Schmidt NW. Epidermal Fatty Acid Binding Protein (E-FABP) is not required for the negation or maintenance of effector and memory T cells following infection with Listeria monocytogenes. PLoS One, 2016, 11(9): e0162427.

 

Stough JMA, Dearth SP, Denny J, LeCleir GR, Schmidt NW*, Campagna SR, Wilhelm SW*. Functional characteristics of the gut microbiome in C57BL/6 mice differentially susceptible to Plasmodium yoelii. Frontiers in Microbiology, 2016, 7:1520.

 

*Co-corresponding authors.

Complete List of Publications