Faculty

Alice Tarun, PhD Assistant Professor E-mail: ast22@pitt.edu Phone: 412-648-5555 Fax: 412-383-8926 Address: 605 Parran Hall 130 DeSoto Street Pittsburgh, PA 15261

Education

BS Biology (Major in Genetics); University of the Philippines at Los Banos
PhD in Comparative Biochemistry; University of California at Berkeley

Research Interests

Plasmodium parasite; Malaria; Functional Genomics; Proteomics; Host-Pathogen Interactions

Research Summary

The Plasmodium parasite causes the deadly disease malaria which is responsible for the deaths of more than a million people yearly, particularly children from sub-Saharan Africa. Global efforts to control malaria continue to be stymied by the lack of a vaccine and the spread of resistance to anti-malarial drugs. This parasite has a complex life cycle that alternates between the mosquito vector and the mammalian host. At each life cycle stage, the parasite has to adapt to a different host cell environment requiring different metabolic strategies and inducing different responses from its host.

The Liver Stage Proteome. My lab is particularly interested in the liver stage of the malaria parasite that develops inside hepatocytes of the mammalian host. The liver stage is the most promising target for protective vaccine development and also a good preventive drug target because it occurs without any clinical symptoms and precedes the pathogenic blood stages. We have recently made great advances in gaining experimental access to liver stages through the use of fluorescent activated cell sorting (FACS) to isolate green fluorescent liver stage-infected hepatocytes. This technique allows us to routinely obtain liver stages from mouse infections and from in vitro infected hepatocytes. In collaboration with the Kappe lab at the Seattle Biomedical Research Institute, we are attempting to conduct a global proteomic analysis of the liver stage parasite not only to study its unique biology but also for the identification of parasite proteins that could be targeted for vaccine and drug development against malaria.

Liver Stage Parasite-host Interactions. Plasmodium is an intracellular parasite that lives inside a vacuole, which constitutes the main interface between the parasite and the host cell. We hypothesize that crucial parasite proteins that mediate host cell interaction and modulation must be located either at this interface or are exported beyond the vacuole to the host hepatocyte. We hope to identify potential parasite proteins exported to the parasite vacuole or the host hepatocyte cytoplasm (i.e. exportome) as well as the host proteins they interact with in order to understand how the parasite is able to modulate the host cell environment during liver stage development.

Functional Genomics. We will use Plasmodium transfection studies in order to understand the function and localization of Plasmodium proteins of interest. In particular, we are interested in identifying genes that may play important roles in liver stage and gametocyte stage development since they could be important targets for vaccine and drug development that could aid in blocking the transmission of malaria.

Recent Publications

• Tarun, A. S., K. Baer, R. F. Dumpit, S. Gray, N. Lejarcegui, U. Frevert and S. H. I. Kappe. 2006. Quantitative isolation and in vivo imaging of malaria parasite liver stages. International Journal of Parasitology. 36(12):1283-93.

• Tarun, A. S., R. F. Dumpit, N. Camargo, M. Labaied, P. Liu, A. Takagi, R. Wang and S.H. I. Kappe. 2007. Protracted sterile protection with Plasmodium yoelii pre-erythrocytic genetically attenuated parasite malaria vaccines is independent of significant liver-stage persistence and is mediated by CD8+ Tcells. Journal of Infectious Diseases. 196(4):608-16.

• Tarun, A. S., X. Peng, R. F. Dumpit, Y. Ogata, H. Silva-Rivera, N. Camargo, T.M. Daly, L.W. Bergman, and S.H. I. Kappe. 2008. A Combined Transcriptome and Proteome Survey of Malaria Parasite Liver Stages.” Proceedings of the National Academy of Sciences, USA. 105(1):305-10.*

• Mikolajczak SA, Silva-Rivera H, Peng X, Tarun AS, Camargo N, Jacobs-Lorena V, Daly TM, Bergman LW, de la Vega P, Williams J, Aly AS, Kappe SH. 2008. Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host. Mol Cell Biol. 2008 Oct;28(20):6196-207. Epub 2008 Aug 18.

• Vaughan; S-Y Chiu; Gowthaman Ramasamy; Ling Li; Malcolm J. Gardner; A. S. Tarun; Stefan H.I. Kappe; Xinxia Peng. Assessment and improvement of the Plasmodium yoelii yoelii genome annotation through comparative analysis. 2008. Bioinformatics . 24: i383-i389.

• Vaughan AM, O'Neill MT, Tarun AS, Camargo N, Phuong TM, Aly AS, Cowman AF, Kappe SH. 2008. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development. Cell Microbiol. 2008 Dec 3. [Epub ahead of print]

• Kumar KA, Baxter P, Tarun AS, Kappe SH, Nussenzweig V. 2009. Conserved protective mechanisms in radiation and genetically attenuated uis3(-) and uis4(-) Plasmodium sporozoites. PLoS ONE. 2009;4(2):e4480. Epub 2009 Feb 13.

• Albuquerque SS, Carret C, Grosso AR, Tarun AS, Peng X, Kappe, SHI, Prudencio M and Mota MM. 2009. Host cell transcriptional profiling during malaria liver stage infection reveals a coordinated and sequential set of biological event. BMC Genomics, in press.