Ashlee V. Moses, Ph.D.

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.

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
Moses, A.V. and H.M. Garnett.  The effect of human cytomegalovirus on the production and biological action of interleukin 1.  J. Infect. Dis. 162:381-388, 1990.

Moses, A.V., F.E. Bloom, C.D. Pauza and J.A. Nelson. Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism.  Proc. Natl. Acad. Sci. USA 90:10474-10478, 1993.

Moses, A.V., C. Ibanez, R. Gaynor, P. Ghazal and J.A. Nelson.  Differential role of long terminal repeat control elements for the regulation of basal and tat-mediated transcription of the human immunodeficiency virus in stimulated and unstimulated primary human macrophages.  J. Virol. 68:298-307, 1994.

Moses, A.V. and J.A. Nelson.  HIV infection of human brain capillary endothelial cells-implications for AIDS dementia.  Adv. Neuroimmunology 4:239-247, 1994.
Fish, K.N., A.S. Depto, A.V. Moses, W. Britt and J.A. Nelson.  Growth kinetics of human cytomegalovirus are altered in monocyte-derived macrophages, J. Virol. 69:3737-3743, 1995.

Moses, A.V., S. Williams, M.L. Heneveld, J. Strussenberg, M. Rarick, M. Loveless, G. Bagby and J.A. Nelson.  HIV infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors.  Blood 87:919-925, 1996.

Moses, A.V., S. G. Stenglein and J.A. Nelson.  HIV infection of the brain microvasculature and its contribution to the AIDS dementia complex.  J. Neuro-AIDS, 85-99, 1996.

Moses, A.V., S.G. Stenglein, J.G. Strussenberg, K. Wehrly, B. Chesebro and J.A. Nelson.  Sequences regulating tropism of HIV-1 for brain capillary endothelial cells map to a unique region on the viral genome.  J. Virol. 70:3401-3406, 1996.
Prudhomme, J.G., I.W. Sherman, K.M. Land, A.V. Moses, S. Stenglein and J.A. Nelson.  Studies of Plasmodium falciparum cytoadherence using immortalized human brain capillary endothelial cells. Intl. J. Parasitology, 26:647-655, 1996.

Moses, A.V., S.E. Williams, J.G. Strussenberg, M.L. Heneveld, R.A. Ruhl, G.C. Bagby and J.A. Nelson.  HIV-1 induction of CD40 on endothelial cells promotes the outgrowth of AIDS-associated B cell lymphomas. Nature Medicine, 3:1242-1249, 1997.

Moses, A., J. Nelson and G.C. Bagby. The influence of human immunodeficiency virus-1 on hematopoiesis. Blood 91:1479-1495, 1998.

Moses, A.V. and L.M. Dallasta. The pathology of primary central nervous system lymphoma (PCNSL) in AIDS. NeuroAIDS Vol.2 (2), 1999.

Moses, A.V., K.N. Fish, R. Ruhl, P.P. Smith, J.G. Strussenberg, L. Zhu, B. Chandran and J.A. Nelson. Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8 (HHV8). J. Virol. 73:6892-6902, 1999.

Dallasta, L.M., L.A. Pasarov, J.E. Esplen, J.V. Werley, A.V. Moses, J.A. Nelson and C.L. Achim.  Blood-brain barrier tight junction disruption in human immunodeficiency virus encephalitis. Am. J. Pathology, 155:1915-1927, 1999.

Blackbourn, D.J., E. Lenette, B. Klencke, A.V. Moses, B. Chandran, M. Weinstein, R.G. Glougau, M.H. Witte, D.L. way, T. Kltzkey, B. Herndier and J.A. Levy. The restricted cellular host range of HHV8. AIDS, 14:1123-1133, 2000.

Zoeteweij, J.P., A.V. Moses, A.S. Rinderknecht, D.A. Davis, W.W. Overwijk, R. Yarchoan, J.M. Orenstein and A. Blauvelt. Targeted inihibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi's sarcoma herpesvirus. Blood, 97:2374-2380, 2001.

Henderson, W.W. and A.V. Moses. Vascular Cell Adhesion Molecules. Encyclopedia of Molecular Medicine, Volume 5, John Wiley and Sons, inc pp3335-3343 2002.

A.V. Moses, M.A. Jarvis, C. Raggo, Y.C. Bell, R. Ruhl, B.G.M. Luukkonen, D.J. Griffith, C. Wait, B.J. Druker, M.C. Heinrich, J.A. Nelson and K. Fruh.  KSHV-induced upregulation of the c-Kit proto-oncogene, as identified by gene expression profiling, is essential for the transformation of endothelial cells.  J. Virol. 76:8383-8399 2002.

A.V. Moses, M.A. Jarvis, C. Raggo, Y.C. Bell, R. Ruhl, B.G.M. Luukkonen, D.J. Griffith, C. Wait, B.J. Druker, M.C. Heinrich, J.A. Nelson and K. Fruh. A functional genomics approach to Kaposi’s sarcoma. Ann. N.Y. Acad. Sci. 957:1-12, 2002.

P. Ancuta, R. Rao, A. Moses, A. Mehle, F.W. Luscinskas and D. Gabuzda. A novel mechanism for CD16+ monocyte transendothelial migration and matrix metalloproteinase-9 induction mediated by fractalkine. J. Exp. Med. 197:1701-1707, 2003.

V. DeFilippis, C. Raggo, A. Moses and K. Fruh. Functional genomics in virology and anti-viral drug discovery. TIBBS, 21:452-457. 2003

W.W. Henderson, R. Ruhl, P. Lewis, M. Bentley, J.A. Nelson and A.V. Moses. HIV-1 Vpu Induces Expression of CD40 in Endothelial Cells and Regulates HIV-induced Adhesion of B Lymphoma Cells. J. Virol. 78:4408-4420 2004.

S.C. McAllister, S.G. Hanson, R.A.. Ruhl, C.M. Raggo, V.R. De Felippis, D. Greenspan, K. Fruh and A.V. Moses. Kaposi’s Sarcoma-associated Herpesvirus (KSHV) Induces Heme Oxygenase-1 Expression and Activity in KSHV-infected Endothelial Cells. Blood 103:3465-3473, 2004.

P. Ancuta, A. Moses, and D. Gabuzda. Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. Immunobiology. 209:11-20, 2004.

S.C. McAllister, I. Messaoudi, S.G. Hanson, J. Nickolich-Zugich and A.V. Moses. Increased efficiency of phorbol ester-induced lytic reactivation of Kaposi’s sarcoma-associated herpesvirus during S-phase. J. Virol. 79:2626-2630, 2005.

S.C. McAllister, K. Früh and A.V. Moses. Functional Genomics and the Development of Pathogenesis-Targeted Therapies for Kaposi’s Sarcoma. Pharmacogenomics, 6:235-44, 2005.

C. Raggo, R. Ruhl, S. McAllister, H. Koon, B.J. Dezube, K. Früh and A.V. Moses. Novel cellular genes essential for transformaton of endothelial cells by Kaposi’s sarcoma-associated herpesvirus. Cancer Research, 65:5084-95, 2005.

M. Mansouri, J. Douglas, P.P. Rose, K. Gouveia, G. Thomas, R.E. Means, A.V. Moses, and K. Früh. Kaposi’s sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells. Blood 108(6):1934-40, 2006.

P.P. Rose, J.M. Carroll, P.A. Carroll, V.R. DeFillipis, M. Lagunoff, A.V. Moses, C.T. Roberts Jr. and K. Früh. The Insulin Receptor is Essential for Virus-induced Tumorigenesis of Kaposi’s Sarcoma. Oncogene 26(14):1995-2005, 2007.

S. McAllister and A.V. Moses. Endothelial cell and lymphocyte-based in vitro systems for understanding KSHV biology. In: “Kaposi’s Sarcoma Herpesvirus: New Perspectives”. Current Topics in Microbiology and Immunology. C. Boshoff and R. Weiss (eds). Springer-Verlag Berlin Heidelberg. 312:211-244, 2007.

P.P Rose, M. Bogyo, A.V. Moses, and K Fruh. Insulin-like growth factor II receptor-mediated retention of cathepsin B is essential for transformation of endothelial cells by Kaposi’s sarcoma-associated herpesvirus. J. Virol., 81:8050-62, 2007.

J.L. Douglas, J.K. Gustin JK, B. Dezube, J.L. Pantanowitz, A.V. Moses. Kaposi's sarcoma: a model of both malignancy and chronic inflammation. Panminerva Med. 49(3):119-38, 2007.

D.N. Streblow, C.N. Kreklywich, T. Andoh, A.V. Moses, J. Dumortier, P.P. Smith, V. Defilippis, K. Fruh, J.A. Nelson and S.L. Orloff.The role of angiogenic and wound repair factors during CMV-accelerated transplant vascular sclerosis in rat cardiac transplants. Am J Transplant. 8(2):277-87, 2008.

J.R. Smith, W.W. Henderson, J.T. Rosenbaum, E.A. Neuwelt, and A.V. Moses. Cultured Human Endothelial Cells Expressing HIV-1 Vpu and Tat Support the Expansion of Malignant B Cells from Primary Central Nervous System Lymphoma. B. J. Opthalmol. 92(2):297-9, 2008.

J. Dumortier, D.N. Streblow, A.V. Moses, J.M. Jacobs, C.N. Kreklywich, D. Camp, R.D. Smith, S.L. Orloff, and J.A. Nelson. 2008. Human Cytomegalovirus Secretome Contains Factors That Induce Angiogenesis and Wound Healing. J. Virol. 82:6524-35, 2008.

D.N. Streblow, J. Dumortier, A.V. Moses, S.L. Orloff, and J.A. Nelson. Mechanisms of cytomegalovirus-accelerated vascular disease: induction of paracrine factors that promote angiogenesis and wound healing. Curr Top Microbiol Immunol. 325:397-415, 2008.

L. Pantanowitz, K. Früh, S. Marconi, A.V. Moses and B.J. Dezube. Pathology of rituximab-induced Kaposi’s sarcoma flare. BMC Clin. Pathol. 8:7, 2008.

M. Mansouri, P.P. Rose, A.V. Moses, and K. Früh. Remodeling of adherens junctions by Kaposi’s sarcoma herpesvirus. J. Virol. 82:9615-28, 2008.

A.V. Moses. In Vitro Endothelial Cell Systems to Study Kaposi Sarcoma. In: Kaposi sarcoma: A model of oncogenesis. Eds:  L. Pantanowiz, J. Stebbing and B.J. Dezube. Research Signpost, India. In Press 2009.

J. L. Douglas, K. Viswanathan, M.N. McCarroll, J.K. Gustin, K. Früh, and A.V. Moses. Vpu Directs the Degradation of the HIV Restriction Factor BST-2/tetherin via a bTrCP-dependent Mechanism. J. Virol., 83:7931-47, 2009.

M. Mansouri, K. Viswanathan, J.L. Douglas, J. Hines, J. Gustin, A.V. Moses, and K. Früh. Molecular mechanism of BST2/tehtherin downregulation by K5/MIR2 of Kaposi’s sarcoma herpesvirus. J. Virol., 83:9672-81, 2009.

L. Pantanowitz, A.V. Moses and B.J. Dezube. The inflammatory component of Kaposi sarcoma.  Exp Mol Pathol. 87:163-5, 2009.