Victoria Jeffers, PhD
Assistant Research Professor
My research focuses on how posttranslational modifications regulate biological pathways in the protozoan parasite Toxoplasma gondii. I am particularly interested in the role of bromodomain proteins, the “readers” of lysine acetylation.
Indiana University School of Medicine
|Advisor: Prof. William Sullivan Jr|
EMBL Network of Excellence
Biomedical Primate Research Centre
|Rijswijk, The Netherlands
University of Heidelberg, Germany
|Advisors: Dr. Clemens Kocken/ Prof. Michael Lanzer|
Dublin City University, Ireland
|2001-2005||B.A. Mod Microbiology
Trinity College Dublin, Ireland
Epigenetic regulation of gene expression is essential to Toxoplasma gondii proliferation and development. The precise factors that mediate the switch in gene expression in response to post-translational modification of histones in Toxoplasma are poorly understood. I am interested in the proteins that “read” post-translational modifications on histones and other gene regulatory factors to recruit transcriptional complexes and fine-tune parasite gene expression.
My work is currently concerned with the regulatory role of bromodomain proteins, which contain the recognition domains for acetylated lysines. Lysine acetylation is not only found on histones, but is distributed throughout the parasite cell on proteins of a variety of cellular functions. Genetic and pharmacological approaches have demonstrated that acetylation is crucial to parasite viability and the bromodomain is an essential component of this pathway. I aim to understand the function of the bromodomain proteins in Toxoplasma, both in the context of epigenetic regulation of gene expression as well as their potential role in modulating cellular signaling through recognition of acetyl marks on non-histone proteins.
Jeffers V, Gao H, Checkley LA, Liu Y, Ferdig MT, Sullivan WJ Jr. Garcinol Inhibits GCN5-Mediated Lysine Acetyltransferase Activity and Prevents Replication of the parasite Toxoplasma gondii. Antimicrobial agents and chemotherapy. 2016; 60(4):2164-70. PMID: 26810649
Bouchut A, Chawla AR, Jeffers V, Hudmon A, Sullivan WJ Jr. Proteome-wide lysine acetylation in cortical astrocytes and alterations that occur during infection with brain parasite Toxoplasma gondii. PLoS one. 2015; 10(3):e0117966. PMID: 25786129
Wang J, Dixon SE, Ting LM, Liu TK, Jeffers V, Croken MM, Calloway M, Cannella D, Hakimi MA, Kim K, Sullivan WJ Jr. Lysine acetyltransferase GCN5b interacts with AP2 factors and is required for Toxoplasma gondii proliferation. PLoS Pathogens. 2014; 10(1):e1003830. PMID: 24391497
Miao J, Lawrence M, Jeffers V, Zhao F, Parker D, Ge Y, Sullivan WJ Jr, Cui L. Extensive lysine acetylation occurs in evolutionarily conserved metabolic pathways and parasite-specific functions during Plasmodium falciparum intraerythrocytic development. Molecular microbiology. 2013; 89(4):660-75. PMID: 23796209
Xue B*, Jeffers V*, Sullivan WJ, Uversky VN. Protein intrinsic disorder in the acetylome of intracellular and extracellular Toxoplasma gondii. Molecular bioSystems. 2013; 9(4):645-57. PMID: 23403842 *equal contribution
Vanagas L, Jeffers V, Bogado SS, Dalmasso MC, Sullivan WJ Jr, Angel SO. Toxoplasma histone acetylation remodelers as novel drug targets. Expert review of anti-infective therapy. 2012; 10(10):1189-201. PMID: 23199404
Jeffers V, Sullivan WJ Jr. Lysine acetylation is widespread on proteins of diverse function and localization in the protozoan parasite Toxoplasma gondii. Eukaryotic cell. 2012; 11(6):735-42. PMID: 22544907
Sullivan WJ Jr, Jeffers V. Mechanisms of Toxoplasma gondii persistence and latency. FEMS microbiology reviews. 2012; 36(3):717-33. PMID: 22091606