How infectious agents, especially newly emergent viruses, cause diseases such as AIDS and AIDS-related cancers is still not clear. Understanding pathogenesis is critical to developing treatments for viral infection.
Ashlee Moses’s laboratory focuses on deciphering mechanisms of viral pathogenesis. Primary research objectives are human immunodeficiency virus type 1 (HIV-1), and Kaposi’s sarcoma herpesvirus (KSHV/HHV8), the infectious agents of AIDS and KS respectively. In KS, an angioproliferative spindle cell tumor, the spindle cells are infected with KSHV. Dr Moses developed a unique endothelial cell-based in vitro model for KS, and she and her colleagues are using this model to understand the role of KSHV infection in angiogenesis and tumorigenesis. They are also developing a mouse model of KS disease. HIV research in the Moses laboratory currently focuses on Vpu, an HIV-1 accessory protein that plays a key role in viral pathogenesis. Recently, using quantitative proteomics in a collaborative study with the Früh laboratory, they discovered that Vpu downregulates surface expression of BST-2/tetherin, a cellular protein that restricts HIV-1 release in the absence of Vpu. They are now elucidating the molecular mechanisms involved in Vpu antagonism of this host anti-viral factor. They are also examining mechanisms through which other enveloped viruses neutralize BST-2, including KSHV and HIV-2/SIV strains that do not express Vpu.
Dr Moses is also involved in collaborative studies with two additional human viral pathogens, the herpesvirus human cytomegalovirus (HCMV) and the flavivirus West Nile Virus (WNV). The HCMV research investigates the role of HCMV in cardiovascular disease and uses novel automated electrical technologies to monitor cell behavior. WNV research involves development of systems to infect immune effector cells and EC to enable an in depth study of WNV immunity and entry to the brain.
Ashlee Moses is a scientist in the Division of Pathobiology and Immunology and an associate professor at the OHSU Vaccine and Gene Therapy Institute. 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 center in 1999.
Totonchy JE, Clepper L, Phillips KG, McCarty OJ, Moses AV. CXCR7 expression disrupts endothelial cell homeostasis and causes ligand-dependent invasion. [PMID: 24710021, PMCID: PMC4049862]
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.) [PMID: 23894550, PMCID: PMC3720914] Print 2013.
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.) [PMID: 23582304, PMCID: PMC3760674] Epub 2013 Apr 10.