Toxoplasma gondii is an intracellular pathogen that has infected over a billion people worldwide.  This parasite sets up a life-long infection in its host that cannot be cured with currently available chemotherapies.  Chronically infected humans that become immunocompromised due to HIV/AIDS are at high risk to develop severe toxoplasmosis that can lead to encephalitis and death. 

Toxoplasma is closely related to other pathogens with a significant impact on human health, including the causative agents of malaria and cryptosporidiosis. What distinguishes Toxoplasma from these organisms is its incredible ability to infect a wide array of hosts, ranging from birds to humans.  We hypothesize that the genes underlying this unique feature play important roles in human infections. 

	Toxoplasma gondii replicating within a human fibroblast host cell.   Abbreviations:  PVM, parasitophorous vacuolar membrane; PN, parasite nuclues; HN, host nucleus; PM, parasite mitochondria; Rh, rhoptries. Photo Credit: Edwin Kamau.

WHO WE ARE: Our lab typically consists of 2-3 graduate students, 1-2 research technicians, and from 4-8 undergraduates.  Postdocs are certainly welcome! Here is our lab circa May, 2015 at a farwell party for Jonathan Harper, Greg Wier and Krystal Flakes.

Row 1:  Jonathan Harper, Greg Wier, Jeff Danielson.  Row 2:  Abby Primack, Krystal Flakes, Emily Klonicki and Germine Alfonse.  Row 3:  Jon Boyle, Elizabeth English, Rachel Coombs.

Our long term goal is to identify factors in the parasite that are important in the host-pathogen interaction and have the potential to become new therapeutic or vaccine targets.  We do this using a variety of approaches, including:

1. Studies of genome structure evolution (both within the Toxoplasma lineage and across recently diverged members of the phylum) to identify genes or loci unique to Toxoplasma compared to its near relatives.  As it turns out, tandemly duplicated loci (like Rhoptry protein 5 and mitochondrial association factor 1) play a big role in distinguishing Toxoplasma from closely-related species.  See our paper in mBio.  

2. Identification of secreted effector proteins that manipulate the host cell.  Interestingly, many of the loci encoding putative secretory proteins are also tandemly expanded loci that have uniquely diversified in Toxoplasma compared to its near relatives.  This list includes mitochondrial association factor 1.

3. Characterization of the transcriptional profile and host response during infection with Toxoplasma and related species.  Toxoplasma shares many (if not all!!!  See Katelyn Walzer's paper in PNAS) of its genes with some near relatives (like Hammondia hammondi).  However, Toxoplasma has a unique developmental and transcriptional profile (see Katelyn Walzer's paper in Eukaryotic Cell), is more lethal in vivo, and has a broader host range than any of these related species.  We use comparative functional genomics to identify candidate loci driving these differences, and then test their impact using gene ablation and overexpression experiments. 

4.  Small molecule screening to identify new druggable targets in Toxoplasma and related apicomplexans.

For another description of our research interests, click here.