The protozoan parasite Toxoplasma gondii is estimated to infect over 2 billion people worldwide, including approximately 20% of Americans. This highly prevalent parasite is adept at establishing a long-term chronic infection that can reactivate to cause serious acute disease in immunocompromised or pregnant people. Although there are some limited treatments available to treat this acute stage of the infection, these therapies often cause toxic side effects, or allergic reactions and can be unsuitable for use in vulnerable patients. Furthermore, the chronic stage of the parasite is currently incurable.
The goal of the Jeffers lab is to understand how the parasite activates or “switches on” gene expression to drive parasite growth and transition in its life cycle and cause disease. This complex process is influenced by a variety of factors, but we are currently interested in epigenetic mechanisms of control, specifically the contribution of bromodomain proteins. These proteins “read” gene activation marks on the chromatin to recruit other complexes that regulate transcription. Determining the role of the bromodomains in regulating Toxoplasma gene expression is not only a fascinating biological question but could also contribute to the development of more effective anti-parasitic drugs. We are now extending our interests in parasite gene expression to investigate precisely how the bromodomain proteins directly regulate the transcriptional initiation machinery and the factors that are necessary to activate a gene. We use an array of genomic, proteomic, molecular and cellular biology approaches to answer these questions.
Fleck, K., Nitz, M., & Jeffers, V. (2021). "Reading" a new chapter in protozoan parasite transcriptional regulation. PLOS PATHOGENS, 17(12). doi:10.1371/journal.ppat.1010056
Maran, S. R., Fleck, K., Monteiro-Teles, N. M., Isebe, T., Walrad, P., Jeffers, V., . . . Moretti, N. (2021). Protein acetylation in the critical biological processes in protozoan parasites. TRENDS IN PARASITOLOGY, 37(9), 815-830. doi:10.1016/j.pt.2021.04.008
Weiss, L. M., Wastling, J., Jeffers, V., Jr, S. W. J., & Kim, K. (2020). Proteomics and posttranslational protein modifications in Toxoplasma gondii. In TOXOPLASMA GONDII: THE MODEL APICOMPLEXAN-PERSPECTIVES AND METHODS, 3RD EDITION (pp. 983-1020). doi:10.1016/B978-0-12-815041-2.00022-0
Kim, K., Jeffers, V., & Jr, S. W. J. (2020). Regulation of gene expression in Toxoplasma gondii. In TOXOPLASMA GONDII: THE MODEL APICOMPLEXAN-PERSPECTIVES AND METHODS, 3RD EDITION (pp. 941-982). doi:10.1016/B978-0-12-815041-2.00021-9
Jeffers, V., Tampaki, Z., Kim, K., & Jr, S. W. J. (2018). A latent ability to persist: differentiation in Toxoplasma gondii. CELLULAR AND MOLECULAR LIFE SCIENCES, 75(13), 2355-2373. doi:10.1007/s00018-018-2808-x
Wang, J., Dixon, S. E., Ting, L. -M., Liu, T. -K., Jeffers, V., Croken, M. M., . . . Jr, S. W. J. (2014). Lysine Acetyltransferase GCN5b Interacts with AP2 Factors and Is Required for Toxoplasma gondii Proliferation. PLOS PATHOGENS, 10(1). doi:10.1371/journal.ppat.1003830
Miao, J., Lawrence, M., Jeffers, V., Zhao, F., Parker, D., Ge, Y., . . . Cui, L. (2013). Extensive lysine acetylation occurs in evolutionarily conserved metabolic pathways and parasite-specific functions during Plasmodium falciparum intraerythrocytic development. MOLECULAR MICROBIOLOGY, 89(4), 660-675. doi:10.1111/mmi.12303
Jeffers, V., & Jr, S. W. J. (2012). Lysine Acetylation Is Widespread on Proteins of Diverse Function and Localization in the Protozoan Parasite Toxoplasma gondii. EUKARYOTIC CELL, 11(6), 735-742. doi:10.1128/EC.00088-12
Jr, S. W. J., & Jeffers, V. (2012). Mechanisms of Toxoplasma gondii persistence and latency. FEMS MICROBIOLOGY REVIEWS, 36(3), 717-733. doi:10.1111/j.1574-6976.2011.00305.x