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    Raffi Van Aroian PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street, Two Biotech, Suite 219
    Worcester MA 01605
    Phone508-856-8169
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentMicrobiology and Physiological Systems

      InstitutionUMMS - School of Medicine
      DepartmentProgram in Molecular Medicine

      InstitutionUMMS - School of Medicine
      DepartmentRNA Therapeutics Institute

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

        Biography 
        awards and honors
        Beckman Foundation2000 - 2003Young Investigator Award
        Burroughs Wellcome Fund2000 - 2003New Investigator Award in Toxicology
        Hellman Foundation1998 - 1999Hellman Faculty Award
        Overview 
        Narrative

        The Aroian Group studies human/animal parasitic nematodes as well as bacterial toxins.

        Our main goal is to discover new and superior treatments for human soil-transmitted helminths (intestinal nematode parasites).  These parasites, aka hookworm, whipworm, and Ascaris (large roundworm) infect upwards of 2 billion people in the world and are leading causes of childhood stunting (physical/cognitive), malutrition, adverse preganancy outcomes, loss of productivity... worldwide.  For example, when once prevalent in the United States, it is estimated that hookworm-infected US children made 40% less money when they grew up than uninfected peers. These parasites are major causes of poverty worldwide.  In addition, the drugs we have now to treat these infections are inadequate to treat some of the parasites and inadequate to eradicate all of them.  We are discovering and developing new de-worming (anthelmintic) compounds with superior characteristics to those currently in use and developing novel delivery strategies to make these compounds available widely and cheaply in the developing world. We are also studying how anthelmintic compounds work and how parasite resistance can be overcome.

        We are also studying how these parasites interact with their host.  In particular, we are interested in studying how these parasites modulate the host and host immune system in a way that might control autoimmune diseases.

        Another group in the laboratory uses the free-living nematode Caenorhabditis elegans to study how bacterial pore-forming toxins work and how the innate immune system protects against bacterial toxin attack.  Since pore-forming toxins are by far the most common mechanism pathogenic bacteria use to attack us, these studies have important implications in the control of bacterial pathogens and diseases, such as those caused by Staphyloccocus and Streptococcus.



        Rotation Projects

        The Aroian Group is actively recruiting graduate students to:

        1. use microbiology and genetics to develop new methods for delivery of protein therapies (anthelmintics) to the GI tract

        2. discovery and mechanism of action studies of new anthelmintics to control soil-transmitted helminths

        3. study how vertebrate hosts and their immune system interact with intestinal nematodes, with the particular goal of controlling autoimmune disease

        4. study innate immune mechanisms that protect animals against pore-forming toxin attack



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Dementiev A, Board J, Sitaram A, Hey T, Kelker MS, Xu X, Hu Y, Vidal-Quist C, Chikwana V, Griffin S, McCaskill D, Wang NX, Hung SC, Chan MK, Lee MM, Hughes J, Wegener A, Aroian RV, Narva KE, Berry C. The pesticidal Cry6Aa toxin from Bacillus thuringiensis is structurally similar to HlyE-family alpha pore-forming toxins. BMC Biol. 2016 Aug 30; 14:71.
          View in: PubMed
        2. Durmaz E, Hu Y, Aroian RV, Klaenhammer TR. Intracellular and Extracellular Expression of Bacillus thuringiensis Crystal Protein Cry5B in Lactococcus lactis for Use as an Anthelminthic. Appl Environ Microbiol. 2015 Dec 18; 82(4):1286-94.
          View in: PubMed
        3. von Hoven G, Neukirch C, Meyenburg M, Füser S, Petrivna MB, Rivas AJ, Ryazanov A, Kaufman RJ, Aroian RV, Husmann M. eIF2a Confers Cellular Tolerance to S. aureus a-Toxin. Front Immunol. 2015; 6:383.
          View in: PubMed
        4. Schwarz EM, Hu Y, Antoshechkin I, Miller MM, Sternberg PW, Aroian RV. Erratum: the genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families. Nat Genet. 2015 Jun; 47(6):689.
          View in: PubMed
        5. Wu CC, Hu Y, Miller M, Aroian RV, Sailor MJ. Protection and Delivery of Anthelmintic Protein Cry5B to Nematodes Using Mesoporous Silicon Particles. ACS Nano. 2015 Jun 23; 9(6):6158-67.
          View in: PubMed
        6. Schwarz EM, Hu Y, Antoshechkin I, Miller MM, Sternberg PW, Aroian RV. The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families. Nat Genet. 2015 Apr; 47(4):416-22.
          View in: PubMed
        7. Somvanshi VS, Ellis BL, Hu Y, Aroian RV. Nitazoxanide: nematicidal mode of action and drug combination studies. Mol Biochem Parasitol. 2014 Jan; 193(1):1-8.
          View in: PubMed
        8. Franks SE, Ebrahimi C, Hollands A, Okumura CY, Aroian RV, Nizet V, McGillivray SM. Novel role for the yceGH tellurite resistance genes in the pathogenesis of Bacillus anthracis. Infect Immun. 2014 Mar; 82(3):1132-40.
          View in: PubMed
        9. Hu Y, Ellis BL, Yiu YY, Miller MM, Urban JF, Shi LZ, Aroian RV. An extensive comparison of the effect of anthelmintic classes on diverse nematodes. PLoS One. 2013; 8(7):e70702.
          View in: PubMed
        10. Hu Y, Miller MM, Derman AI, Ellis BL, Monnerat RG, Pogliano J, Aroian RV. Bacillus subtilis strain engineered for treatment of soil-transmitted helminth diseases. Appl Environ Microbiol. 2013 Sep; 79(18):5527-32.
          View in: PubMed
        11. Urban JF, Hu Y, Miller MM, Scheib U, Yiu YY, Aroian RV. Bacillus thuringiensis-derived Cry5B has potent anthelmintic activity against Ascaris suum. PLoS Negl Trop Dis. 2013; 7(6):e2263.
          View in: PubMed
        12. Los FC, Randis TM, Aroian RV, Ratner AJ. Role of pore-forming toxins in bacterial infectious diseases. Microbiol Mol Biol Rev. 2013 Jun; 77(2):173-207.
          View in: PubMed
        13. Los FC, Ha C, Aroian RV. Neuronal Goa and CAPS regulate behavioral and immune responses to bacterial pore-forming toxins. PLoS One. 2013; 8(1):e54528.
          View in: PubMed
        14. Hui F, Scheib U, Hu Y, Sommer RJ, Aroian RV, Ghosh P. Structure and glycolipid binding properties of the nematicidal protein Cry5B. Biochemistry. 2012 Dec 11; 51(49):9911-21.
          View in: PubMed
        15. Hu Y, Zhan B, Keegan B, Yiu YY, Miller MM, Jones K, Aroian RV. Mechanistic and single-dose in vivo therapeutic studies of Cry5B anthelmintic action against hookworms. PLoS Negl Trop Dis. 2012; 6(11):e1900.
          View in: PubMed
        16. Hu Y, Aroian RV. Bacterial pore-forming proteins as anthelmintics. Invert Neurosci. 2012 Jun; 12(1):37-41.
          View in: PubMed
        17. Kho MF, Bellier A, Balasubramani V, Hu Y, Hsu W, Nielsen-LeRoux C, McGillivray SM, Nizet V, Aroian RV. The pore-forming protein Cry5B elicits the pathogenicity of Bacillus sp. against Caenorhabditis elegans. PLoS One. 2011; 6(12):e29122.
          View in: PubMed
        18. Kao CY, Los FC, Huffman DL, Wachi S, Kloft N, Husmann M, Karabrahimi V, Schwartz JL, Bellier A, Ha C, Sagong Y, Fan H, Ghosh P, Hsieh M, Hsu CS, Chen L, Aroian RV. Global functional analyses of cellular responses to pore-forming toxins. PLoS Pathog. 2011 Mar; 7(3):e1001314.
          View in: PubMed
        19. Los FC, Kao CY, Smitham J, McDonald KL, Ha C, Peixoto CA, Aroian RV. 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. 2011 Feb 17; 9(2):147-57.
          View in: PubMed
        20. Balla KM, Lugo-Villarino G, Spitsbergen JM, Stachura DL, Hu Y, Bañuelos K, Romo-Fewell O, Aroian RV, Traver D. Eosinophils in the zebrafish: prospective isolation, characterization, and eosinophilia induction by helminth determinants. Blood. 2010 Nov 11; 116(19):3944-54.
          View in: PubMed
        21. Hu Y, Platzer EG, Bellier A, Aroian RV. Discovery of a highly synergistic anthelmintic combination that shows mutual hypersusceptibility. Proc Natl Acad Sci U S A. 2010 Mar 30; 107(13):5955-60.
          View in: PubMed
        22. Hu Y, Georghiou SB, Kelleher AJ, Aroian RV. Bacillus thuringiensis Cry5B protein is highly efficacious as a single-dose therapy against an intestinal roundworm infection in mice. PLoS Negl Trop Dis. 2010 Mar 02; 4(3):e614.
          View in: PubMed
        23. Chen CS, Bellier A, Kao CY, Yang YL, Chen HD, Los FC, Aroian RV. WWP-1 is a novel modulator of the DAF-2 insulin-like signaling network involved in pore-forming toxin cellular defenses in Caenorhabditis elegans. PLoS One. 2010 Mar 02; 5(3):e9494.
          View in: PubMed
        24. Bellier A, Chen CS, Kao CY, Cinar HN, Aroian RV. Hypoxia and the hypoxic response pathway protect against pore-forming toxins in C. elegans. PLoS Pathog. 2009 Dec; 5(12):e1000689.
          View in: PubMed
        25. Hu Y, Xiao SH, Aroian RV. The new anthelmintic tribendimidine is an L-type (levamisole and pyrantel) nicotinic acetylcholine receptor agonist. PLoS Negl Trop Dis. 2009; 3(8):e499.
          View in: PubMed
        26. McGillivray SM, Ebrahimi CM, Fisher N, Sabet M, Zhang DX, Chen Y, Haste NM, Aroian RV, Gallo RL, Guiney DG, Friedlander AM, Koehler TM, Nizet V. ClpX contributes to innate defense peptide resistance and virulence phenotypes of Bacillus anthracis. J Innate Immun. 2009; 1(5):494-506.
          View in: PubMed
        27. Kao CY, Los FC, Aroian RV. Nervous about immunity: neuronal signals control innate immune system. Nat Immunol. 2008 Dec; 9(12):1329-30.
          View in: PubMed
        28. Bischof LJ, Kao CY, Los FC, Gonzalez MR, Shen Z, Briggs SP, van der Goot FG, Aroian RV. Activation of the unfolded protein response is required for defenses against bacterial pore-forming toxin in vivo. PLoS Pathog. 2008 Oct; 4(10):e1000176.
          View in: PubMed
        29. Li XQ, Wei JZ, Tan A, Aroian RV. Resistance to root-knot nematode in tomato roots expressing a nematicidal Bacillus thuringiensis crystal protein. Plant Biotechnol J. 2007 Jul; 5(4):455-64.
          View in: PubMed
        30. Barrows BD, Griffitts JS, Aroian RV. Resistance is non-futile: resistance to Cry5B in the nematode Caenorhabditis elegans. J Invertebr Pathol. 2007 Jul; 95(3):198-200.
          View in: PubMed
        31. Aroian R, van der Goot FG. Pore-forming toxins and cellular non-immune defenses (CNIDs). Curr Opin Microbiol. 2007 Feb; 10(1):57-61.
          View in: PubMed
        32. Barrows BD, Haslam SM, Bischof LJ, Morris HR, Dell A, Aroian RV. Resistance to Bacillus thuringiensis toxin in Caenorhabditis elegans from loss of fucose. J Biol Chem. 2007 Feb 2; 282(5):3302-11.
          View in: PubMed
        33. Cappello M, Bungiro RD, Harrison LM, Bischof LJ, Griffitts JS, Barrows BD, Aroian RV. A purified Bacillus thuringiensis crystal protein with therapeutic activity against the hookworm parasite Ancylostoma ceylanicum. Proc Natl Acad Sci U S A. 2006 Oct 10; 103(41):15154-9.
          View in: PubMed
        34. Barrows BD, Griffitts JS, Aroian RV. Caenorhabditis elegans carbohydrates in bacterial toxin resistance. Methods Enzymol. 2006; 417:340-58.
          View in: PubMed
        35. Bischof LJ, Huffman DL, Aroian RV. Assays for toxicity studies in C. elegans with Bt crystal proteins. Methods Mol Biol. 2006; 351:139-54.
          View in: PubMed
        36. Griffitts JS, Aroian RV. Many roads to resistance: how invertebrates adapt to Bt toxins. Bioessays. 2005 Jun; 27(6):614-24.
          View in: PubMed
        37. Griffitts JS, Haslam SM, Yang T, Garczynski SF, Mulloy B, Morris H, Cremer PS, Dell A, Adang MJ, Aroian RV. Glycolipids as receptors for Bacillus thuringiensis crystal toxin. Science. 2005 Feb 11; 307(5711):922-5.
          View in: PubMed
        38. Huffman DL, Abrami L, Sasik R, Corbeil J, van der Goot FG, Aroian RV. Mitogen-activated protein kinase pathways defend against bacterial pore-forming toxins. Proc Natl Acad Sci U S A. 2004 Jul 27; 101(30):10995-1000.
          View in: PubMed
        39. Huffman DL, Bischof LJ, Griffitts JS, Aroian RV. Pore worms: using Caenorhabditis elegans to study how bacterial toxins interact with their target host. Int J Med Microbiol. 2004 Apr; 293(7-8):599-607.
          View in: PubMed
        40. Rappleye CA, Tagawa A, Le Bot N, Ahringer J, Aroian RV. Involvement of fatty acid pathways and cortical interaction of the pronuclear complex in Caenorhabditis elegans embryonic polarity. BMC Dev Biol. 2003 Oct 03; 3:8.
          View in: PubMed
        41. Griffitts JS, Huffman DL, Whitacre JL, Barrows BD, Marroquin LD, Müller R, Brown JR, Hennet T, Esko JD, Aroian RV. Resistance to a bacterial toxin is mediated by removal of a conserved glycosylation pathway required for toxin-host interactions. J Biol Chem. 2003 Nov 14; 278(46):45594-602.
          View in: PubMed
        42. Wei JZ, Hale K, Carta L, Platzer E, Wong C, Fang SC, Aroian RV. Bacillus thuringiensis crystal proteins that target nematodes. Proc Natl Acad Sci U S A. 2003 Mar 4; 100(5):2760-5.
          View in: PubMed
        43. Rappleye CA, Tagawa A, Lyczak R, Bowerman B, Aroian RV. The anaphase-promoting complex and separin are required for embryonic anterior-posterior axis formation. Dev Cell. 2002 Feb; 2(2):195-206.
          View in: PubMed
        44. Griffitts JS, Whitacre JL, Stevens DE, Aroian RV. Bt toxin resistance from loss of a putative carbohydrate-modifying enzyme. Science. 2001 Aug 3; 293(5531):860-4.
          View in: PubMed
        45. Tagawa A, Rappleye CA, Aroian RV. Pod-2, along with pod-1, defines a new class of genes required for polarity in the early Caenorhabditis elegans embryo. Dev Biol. 2001 May 15; 233(2):412-24.
          View in: PubMed
        46. Marroquin LD, Elyassnia D, Griffitts JS, Feitelson JS, Aroian RV. Bacillus thuringiensis (Bt) toxin susceptibility and isolation of resistance mutants in the nematode Caenorhabditis elegans. Genetics. 2000 Aug; 155(4):1693-9.
          View in: PubMed
        47. Rappleye CA, Paredez AR, Smith CW, McDonald KL, Aroian RV. The coronin-like protein POD-1 is required for anterior-posterior axis formation and cellular architecture in the nematode caenorhabditis elegans. Genes Dev. 1999 Nov 1; 13(21):2838-51.
          View in: PubMed
        48. Aroian RV, Field C, Pruliere G, Kenyon C, Alberts BM. Isolation of actin-associated proteins from Caenorhabditis elegans oocytes and their localization in the early embryo. EMBO J. 1997 Apr 1; 16(7):1541-9.
          View in: PubMed
        49. Aroian RV, Lesa GM, Sternberg PW. Mutations in the Caenorhabditis elegans let-23 EGFR-like gene define elements important for cell-type specificity and function. EMBO J. 1994 Jan 15; 13(2):360-6.
          View in: PubMed
        50. Aroian RV, Carta L, Kaloshian I, Sternberg PW. A Free-living Panagrolaimus sp. from Armenia Can Survive in Anhydrobiosis for 8.7 Years. J Nematol. 1993 Sep; 25(3):500-2.
          View in: PubMed
        51. Aroian RV, Levy AD, Koga M, Ohshima Y, Kramer JM, Sternberg PW. Splicing in Caenorhabditis elegans does not require an AG at the 3' splice acceptor site. Mol Cell Biol. 1993 Jan; 13(1):626-37.
          View in: PubMed
        52. Aroian RV, Sternberg PW. Multiple functions of let-23, a Caenorhabditis elegans receptor tyrosine kinase gene required for vulval induction. Genetics. 1991 Jun; 128(2):251-67.
          View in: PubMed
        53. Han M, Aroian RV, Sternberg PW. The let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans. Genetics. 1990 Dec; 126(4):899-913.
          View in: PubMed
        54. Aroian RV, Koga M, Mendel JE, Ohshima Y, Sternberg PW. The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily. Nature. 1990 Dec 20-27; 348(6303):693-9.
          View in: PubMed
        55. Russell CT, Aroian R, Arghavani M, Nock K. Interplanetary magnetic field enhancements and their association with the asteroid 2201 oljato. Science. 1984 Oct 5; 226(4670):43-5.
          View in: PubMed
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