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Victoria Jeffers, PhD

Assistant Research Professor

Research Interest
 

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.


Education
 

2010-2015  Postdoctoral Fellow  
Indiana University School of Medicine 
  Advisor: Prof. William Sullivan Jr
   
2006-2010  PhD
EMBL Network of Excellence
Biomedical Primate Research Centre
  Rijswijk, The Netherlands
University of Heidelberg, Germany
  Advisors: Dr. Clemens Kocken/ Prof. Michael Lanzer
   
2005-2006 M.Sc. Bioinformatics
Dublin City University, Ireland
   
2001-2005 B.A. Mod Microbiology
Trinity College Dublin, Ireland

 

Research


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.

Publications


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
 


Department of Pharmacology and Toxicology | 635 Barnhill Drive, MS A401 | Indianapolis, IN 46202