UC San Diego SearchMenu

Raffi Aroian

Research

The Aroian Group researches infectious diseases and parasites. Our mission is to discover new cures and new basic information that leads to cures for major diseases that afflict humankind, namely intestinal roundworms and bacterial pathogens.

A major focus of our group is soil-transmitted helminths, aka intestinal roundworms or nematodes. These parasites include hookworms (Ancylostoma duodenale, Necator americanus), whipworm (Trichuris trichiura), giant roundworms (Ascaris lumbricoides), and threadworms (Strongyloides stercoralis). We maintain and work with many of these parasites, or close relatives, in our laboratory. These parasites infect upwards of 2 billion people in the world and are the leading source of disease in children worldwide. We have uncovered that crystal proteins made by the soil bacterium Bacillus thuringiensis can cure animals infected with intestinal roundworms. We are studying the mechanisms of how crystal proteins work to kill roundworms as well as optimizing crystal proteins for use in the clinic. Our group is also a leader in using Caenorhabditis elegans to study the mechanism of action of anti-roundworm drugs (anthelmintics) being used clinically around the world.

figure 1

Another focus of our group is studying how our cells neutralize pore-forming proteins. Pore-forming proteins are the most common class of toxins made by bacteria that cause disease in humans. Our group uses the nematode Caenorhabditis elegans to study the molecular, genetic, and cell biological path ways by which cells under attack from these toxins defend themselves and fight off bacterial infection. Our particular focus is on the role of intracellular vesicle trafficking pathways, such as RAB-5 and RAB-11, and mitogen-activated protein kinase pathways, such as p38 and JNK, in cellular defenses against pore-forming proteins. The goal of this research is to develop new cures for bacterial infections that are becoming more difficult to treat because of antibiotic resistance

Publications

  • Hu, Y.H., Xiao, S.H., and Aroian, R.V. (2009). The new anthelmintic tribendimidine is an L-type nicotinic acetylcholine receptor agonist. PLoS Negl Trop Dis 3(8):e499.
  • Bellier, A., Chen, C.S., Kao, C.Y., Cinar, H.N., and Aroian, R.V. (2009). Hypoxia and the hypoxic response pathway protect against pore-forming toxins in C. elegans. PLoS Pathogens 5(12):e1000689.
  • Hu, Y., Georghiou, S.B., Kelleher, A.J., and Aroian, R.V. (2010).Bacillus thuringiensisCry5B protein is highly efficacious as a single-dose therapy against an intestinal roundworm infection in mice. PLoS Negl Trop Dis 4(3):e614.
  • Hu, Y., Platzer, E.G., Bellier, A., and Aroian, R.V. (2010). Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility. Proc Natl Acad Sci 107(13):5955-5960.
  • Los, F.C., Kao, C.Y., Smitham, J., McDonald, K.L., Ha, C., Peixoto, C.A., and Aroian, R.V. (2011). RAB-5- and RAB-11-dependent vesicle-trafficking pathways are required for plasma membrane repair after attack by bacterial pore-forming toxin. Cell Host Microbe 17;9(2):147-157.
  • Kao, C.Y., Los, F.C., Huffman, D.L., Wachi, S., Kloft, N., Husmann, M., Karabrahimi, V., Schwartz, J.L., Bellier, A., Ha, C., Sagong, Y., Fan, H., Ghosh, P., Hsieh, M., Hsu, C.S., Chen, L., and Aroian, R.V. (2011). Global functional analyses of cellular responses to pore-forming toxins. PLoS Pathog. 7(3):e1001314.
  • Kho, M.F., Bellier, A., Balasubramani, V., Hu, Y., Hsu, W., Nielsen-LeRoux, C., McGillivray, S.M., Nizet, V., and Aroian, R.V. (2011). The pore-forming protein Cry5B elicits the pathogenicity of Bacillus sp. against Caenorhabditis elegans. PLoS One 6(12):e29122.

Biography

Raffi Aroian received his Ph.D. from the California Institute of Technology. His postdoctoral studies were carried out at UCSF, where he was a Helen Hayes Whitney Fellow and a Senior Postdoctoral Fellow of the American Cancer Society. He is the recipient of a New Investigators Award in Toxicological Sciences from the Burroughs-Wellcome Foundation and a Beckman Foundation Young Investigator.