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Rebecca Tweedell

Class 2012
Education BS, Purdue University West Lafayette
Email rtweede1@jhmi.edu
Mentor

Dr. Rhoel Dinglasan

Research Interests

The Grad School Grind Blog

Malaria is a devastating disease that affects over 250 million people each year and causes over 700,000 deaths, mainly in children. Plasmodium falciparum is one of the major parasites responsible for morbidity and mortality. This parasite is transmitted to humans as a sporozoite (one of the parasite’s developmental stages) through the bite of an infected female anopheline mosquito during a blood meal. Once injected by the mosquito into the dermis of a human, the sporozoite travels to the bloodstream and makes its way to the liver. It then traverses the sinusoidal barrier, passing through Kupffer cells (KCs), to infect a hepatocyte. While in the hepatocyte, the infection is silent, presenting no clinical symptoms. Meanwhile, the parasite is hard at work maturing, multiplying, and preparing for its cyclical invasion of red blood cells as merozoites, which causes clinical disease. The liver stage is a crucial step in the parasite’s lifecycle; however, this stage has not been well studied. By gaining a thorough understanding of the liver stage, we can improve our abilities to prevent this deadly disease. Although KCs, which are liver macrophages responsible for phagocytosing pathogens and activating an immune response, appear to be a gateway for sporozoites into the liver, very little is known about parasite interactions with these cells. My project focuses on examining sporozoite entry into the liver via traversal of liver-resident KCs. Proteins on the surface of the KC involved in recognition by the sporozoite are unknown, as are many of the KC pathways affected by subsequent cell traversal. My project aims to answer the question of how the sporozoite (1) recognizes and attaches to a KC prior to cell traversal and then (2) traverses the cell without activating an immune response.

Publications

Tweedell RE, Tao D, Dinglasan RRD. The cellular and proteomic response of primary and immortalized murine Kupffer cells following immune stimulation diverges from that of monocyte-derived macrophages. Proteomics. 2015. 15: 545-553. PMID 25266554

Tao D, King JG, Tweedell RE, Jost PJ, Boddey JA, Dinglasan RR. The acute transcriptomic and proteomic response of HC-04 hepatoma cells to hepatocyte growth factor and its implications for Plasmodium falciparum sporozoite invasion. Mol Cell Proteomics. 2014. 13(5): 1153-1164. PMID 24532842