William Sullivan, Ph.D.
Professor of Pharmacology & Toxicology
Professor of Microbiology and Immunology
Description and summary of research focus of the laboratory
We study the regulation of gene expression in a protozoan parasite called Toxoplasma gondii. Toxoplasma, a relative of the malaria parasite, causes congenital birth defects, as well as opportunistic infection in AIDS, cancer chemotherapy, and organ transplant patients. There is also recent evidence suggesting that this parasite is linked to neurological disorders, such as schizophrenia and behavior modification. We hypothesize that the proteins controlling gene expression at epigenetic, transcriptional, and translational levels may represent novel drug targets to fight Toxoplasma and other infectious diseases. We are particularly interested in the molecular mechanisms that govern how the parasite switches between its rapidly proliferating form and its latent cyst form.
Since the conversion to the cyst form is a stress-induced process, my laboratory has focused on investigating cellular stress pathways in this pathogen. We have discovered that eukaryotic initiation factor-2 (eIF2) phosphorylation plays a key role in cyst formation; eIF2 regulates protein translation in response to stress. We have also discovered numerous histone modifying enzymes that function to alter gene expression during stress-induced cyst formation, suggesting that epigenetic mechanisms also mediate cyst formation. Ongoing studies continue to examine the contributions of translational and transcriptional control in this clinically relevant protozoan. Not only does our research promise to illuminate new approaches to eliminate latent infections, but it also will provide valuable insight into the evolution of cellular signaling and gene regulation.
- Joyce BR, Konrad C, Wek RC, Sullivan Jr WJ. (2011) Translation control is critical during acute and chronic stages of toxoplasmosis infection. Expert Rev Anti Infect Ther 9:1-3.
- Naguleswaran A, Elias EV, McClintick J, Edenberg H, Sullivan Jr WJ. (2010) Toxoplasma gondii lysine acetyltransferase GCN5-A functions in the cellular response to alkaline stress and expression of cyst genes. PLoS Pathogens, 6:e1001232.
- Joyce BR, Queener SF, Wek RC, Sullivan Jr WJ. (2010) Phosphorylation of eIF2α promotes the extracellular survival of obligate intracellular parasite Toxoplasma gondii. Proc Natl Acad Sci USA, 107:17200-5.
- Zhang M, Fennell C, Ranford-Cartwright L, Sakthivel R, Gueirard P, Meister S, Caspi A, Doerig C, Nussenzweig RS, Tuteja R, Sullivan Jr WJ, Roos DS, Fontoura BM, Ménard R, Winzeler EA, Nussenzweig V. (2010) The Plasmodium eukaryotic initiation factor-2a kinase IK2 controls the latency of sporozoites in the mosquito salivary glands. J Exp Med. 207:1465-74. (featured in Research Highlights in Nature Reviews Microbiology, Aug 2010)
- Dixon SE, Stilger KL, Elias EV, Naguleswaran A, Sullivan Jr WJ. (2010) A decade of epigenetic research in Toxoplasma gondii. Mol Biochem Parasitol. 173:1-9.
- Vonlaufen N, Naguleswaran A, Coppens I, Sullivan Jr WJ. (2010) MYST-family lysine acetyltransferase facilitates ataxia telangiectasia mutated (ATM) kinase-mediated DNA damage response in Toxoplasma gondii. J Biol Chem. 285:11154-61.
- B.S., 1992: Frostburg State University, Frostburg, MD
- Ph.D., 1997: University of Pennsylvania, Philadelphia, PA
- Postdoctoral, 1998-2000: ELANCO/Eli Lilly & Co., Greenfield, IN
- Assistant Scientist, 2000-2003: Indiana University School of Medicine, Indianapolis, IN