OHSU

ASHLEE V. MOSES

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 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 currently studying the role of two KSHV-induced cellular proteins, the chemokine receptor CXCR7 and the inducible enzyme heme-oxygenase-1 (HO-1) in the tumorgenic process.  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.  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, and the implications for HIV persistence and pathogenesis. They are also examining mechanisms through which other enveloped viruses neutralize BST-2.

Dr. Moses is also collaborating with Dr. Wong 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 may represent a promising 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 will focus on blood-CNS and blood-spinal cord barriers and JMRV infection of endothelial cells from these specialized tissue sites.

Biography

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.

Key Publications

Douglas JL, Whitford JG, Moses AV. (2009) Characterization of c-Kit expression and activation in KSHV-infected endothelial cells. Virology. 390:174-185.

Douglas JL, Viswanathan K, McCarroll MN, Gustin JK, Früh K, Moses AV. (2009) Vpu directs the degradation of the HIV restriction factor BST-2/tetherin via beta TrCP-dependent mechanism. J Virol. 83:7931-7947.

Moses AV. (2010) In vitro endothelial cell systems to study Kaposi sarcoma. In: "Kaposi sarcoma: A model of oncogenesis". L. Pantanowiz, J. Stebbing and B.J. Dezube (Eds). Research Signpost, India. pp 57-73.

Gustin JK, Douglas JL, Bai Y, Moses AV. (2012) Ubiquitination of BST-2 protein by HIV-1 Vpu protein does not require lysine, serine, or threonine residues withing the BST-2 cytoplasmic domain.  J Biol Chem. Apr 27;287(18):14837-50.  doi:10,1074/jbc.M112.349928. Epub 2012 Mar 1.

Douglas JL, Bai Y, Gustin JK, Moses AV.  (2013) 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.Jul 5;441(2):182-196.  doi: 10.1016/j.virol.2013.03.015. Epub 2013 April 10.

Totonchy JE, Osborn JM, Botto S, Clepper L, Moses AV.  (2013) Aberrant proliferation in CXCR7+ endothelial cells via degradation of the retinoblastoma protein.  PloS One. Jul 23;8(7)e69828. doi:10.1371/journal.pone.0069828.

See a full listing of Dr. Moses's publications.