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.
Courses Taught
- BMS 655: Human and Animal Parasites
- BMS 703: Infectious Disease and Health
- BMS 795W: Investigations Biomedical Sci
- BMS 799H: Senior Honors Thesis
- BMS/MICR 735/835: Molecular Cellular Parasitol
- INCO 590: Student Research Experience
- INCO 790: Advanced Research Experience
- MCBS 997: Seminar
- MCBS 999: Doctoral Research
Research Interests
- Antimicrobials
- Cellular Biology
- Drug Discovery
- Epigenetics
- Gene Expression
- Gene Regulation
- Genetic Manipulation
- Infectious Diseases/Agents
- Microbes
- Microbiology
- Molecular Biology
- Parasitology
- Pathogenesis
- Transcription
Selected Publications
Huet, D., & Jeffers, V. (2024). Seeing the unseen: illuminating Toxoplasma gondii's metabolic manipulation.. mBio, 15(8), e0121124. doi:10.1128/mbio.01211-24
Jeffers, V. (2024). Histone code: a common language and multiple dialects to meet the different developmental requirements of apicomplexan parasites.. Curr Opin Microbiol, 79, 102472. doi:10.1016/j.mib.2024.102472
Phillips, M., Malone, K. L., Boyle, B. W., Montgomery, C., Kressy, I. A., Joseph, F. M., . . . Glass, K. C. (2024). Impact of Combinatorial Histone Modifications on Acetyllysine Recognition by the ATAD2 and ATAD2B Bromodomains.. J Med Chem, 67(10), 8186-8200. doi:10.1021/acs.jmedchem.4c00210
Baptista, C. G., Hosking, S., Gas-Pascual, E., Ciampossine, L., Abel, S., Hakimi, M. -A., . . . Blader, I. J. (2023). Toxoplasma gondii F-Box Protein L2 Silences Feline-Restricted Genes Necessary for Sexual Commitment.. bioRxiv. doi:10.1101/2023.12.18.572150
Fleck, K., McNutt, S., Chu, F., & Jeffers, V. (2023). An apicomplexan bromodomain protein, TgBDP1, associates with diverse epigenetic factors to regulate essential transcriptional processes in Toxoplasma gondii.. mBio, 14(4), e0357322. doi:10.1128/mbio.03573-22
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