How infectious agents, especially newly emergent viruses, cause diseases including AIDS and AIDS-related cancers is still not completely understood. Understanding viral pathogenesis is critical to developing treatments for viral infection and infection-associated diseases.
Ashlee Moses's laboratory studies viral pathogenesis with a particular emphasis on gamma herpesviruses and the development of appropriate cell-based and animal translational disease models. A major focus is the study of Kaposi sarcoma herpesvirus (KSHV), with the goal of deciphering the virus-host interaction and identifying therapeutic targets for KSHV-associated cancers, particularly Kaposi sarcoma (KS), an angioproliferative spindle cell tumor. Dr. Moses developed a unique endothelial cell-based in vitro model for KS, and she and her colleagues are using this model in coordination with molecular and genetic techniques to understand the role of KSHV infection in angiogenesis and tumorigenesis. Current projects are focused on understanding the role of HO-1 (a heme-degrading enzyme induced by KSHV infection that is robustly expressed in KS tumors) in KSHV pathogenesis and on determining how and why KSHV manipulates iron metabolism and antioxidant defense pathways in infected cells. They are also using a macaque homolog of KSHV, rhesus rhadinovirus (RRV), in order to benefit from a non-human primate model of disease. This work will increase understanding of KSHV pathogenesis and may identify novel therapeutic targets for KS treatment. KSHV-induced cellular proteins are also implicated in the development of other cancers. Thus, this line of research has broader implications for cancer development and therapy. Dr. Moses is also collaborating with VGTI researchers to understand the role of a novel simian herpesvirus, JM rhadinovirus (JMRV), in Japanese macaque encephalomyelitis (JME), a spontaneous inflammatory demyelinating disease that occurs in the ONPRC's Japanese macaque colony. JME represents a promising animal model for demyelinating conditions such as multiple sclerosis for which a viral and/or autoimmune component is indicated. Work by the Moses laboratory in the JME model focuses on blood-CNS and blood-spinal cord barriers and JMRV infection of endothelial cells from these specialized tissue sites. Dr. Moses has also worked with several other viruses including HIV, SIV, Zika virus, West Nile virus and cytomegalovirus.
Ashlee Moses is an Associate Scientist in the Division of Pathobiology and Immunology at the OHSU Oregon National Primate Research Center (ONPRC) and a Professor at the OHSU Vaccine and Gene Therapy Institute (VGTI). After being awarded her B.S. at Rhodes University in 1985 and an honors degree at the University of the Witwatersrand in 1986, both in South Africa, she earned her Ph.D. at the University of Wollongong in Australia in 1990. She conducted postdoctoral research at the Scripps Research Institute in San Diego and in the Department of Molecular Microbiology and Immunology in the School of Medicine, OHSU, and became an Assistant Professor at OHSU before joining the ONPRC in 1999.
- Gustin JK, Douglas JL, Bai Y, Moses AV. Ubiquitination of BST-2 protein by HIV-1 Vpu protein does not require lysine, serine, or threonine residues within the BST-2 cytoplasmic domain. J Biol Chem. 2012 Apr 27;287(18):14837-50. doi: 10.1074/jbc.M112.349928. Epub 2012 Mar 1. PubMed PMID: 22383521; PubMed Central. PMCID: PMC3340234.
- Douglas JL, Bai Y, Gustin JK, Moses AV. A comparative mutational analysis of HIV-1 Vpu subtypes B and C for the identification of determinants required to counteract BST-2/Tetherin and enhance viral egress. Virology. 2013 Jul 5;441(2):182-96. doi: 10.1016/j.virol.2013.03.015. Epub 2013 Apr 10. PubMed PMID: 23582304; PubMed Central PMCID: PMC3760674.
- Totonchy JE, Osborn JM, Botto S, Clepper L, Moses AV. Aberrant proliferation in CXCR7+ endothelial cells via degradation of the retinoblastoma protein. PLoS One. 2013 Jul 23;8(7):e69828. doi: 10.1371/journal.pone.0069828. Print 2013. PubMed PMID: 23894550; PubMed Central PMCID: PMC3720914.
- Totonchy JE, Clepper L, Phillips KG, McCarty OJT, Moses AV. CXCR7 expression disrupts endothelial cell homeostasis and causes ligand-dependent invasion. Cell Adh Migr. 2014 Mar 1; 8(2): 165–176. Published online 2014 Mar 20. doi: 10.4161/cam.28495. PMCID: PMC4049862.
- Botto S, Totonchy JE, Gustin JK, Moses AV. Kaposi Sarcoma Herpesvirus Induces HO-1 during De Novo Infection of Endothelial Cells via Viral miRNA-Dependent and -Independent Mechanisms. mBio. 2015 May-Jun; 6(3): e00668-15. Published online 2015 Jun 4. doi: 10.1128/mBio.00668-15. PMCID: PMC4462627.
- Botto S, Gustin JK, Moses AV. The Heme Metabolite Carbon Monoxide Facilitates KSHV Infection by Inhibiting TLR4 Signaling in Endothelial Cells. Front Microbiol. 2017; 8: 568. Published online 2017 Apr 3. doi: 10.3389/fmicb.2017.00568. PMCID: PMC5376558.
- Garrigues HJ, Howard K, Barcy S, Ikoma M, Moses AV, Deutsch GH, Wu D, Ueda K, Rose TM. Full-Length Isoforms of Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Accumulate in the Cytoplasm of Cells Undergoing the Lytic Cycle of Replication. J Virol. 2017 Dec 15; 91(24): e01532-17. Prepublished online 2017 Oct 4. Published online 2017 Nov 30. doi: 10.1128/JVI.01532-17. PMCID: PMC5709576.
- Hirsch AJ, Roberts VHL, Grigsby PL, Haese N, Schabel MC, Wang X, Lo JO, Liu Z, Kroenke CD, Smith JL, Kelleher M, Broeckel R, Kreklywich CN, Parkins CJ, Denton M, Smith P, DeFilippis V, Messer M, Nelson JA, Hennebold JD, Grafe M, Colgin L, Lewis A, Ducore R, Swanson T, Legasse AW, Axthelm MK, MacAllister R, Moses AV, Morgan TK, Frias AE, Streblow DN. Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. Nat Commun. 2018; 9: 263. Published online 2018 Jan 17. doi: 10.1038/s41467-017-02499-9. PMCID: PMC5772047.