Ashlee V. Moses, Ph.D.

Biography
After receiving her B.SC. from Rhodes University in Grahamstown, South Africa in 1985, Ashlee Moses pursued and completed a Ph.D. in Immunology from the University of Wollongong in Australia in 1990. Dr. Moses then completed two Postdoctoral Fellowships, one in the Department of Immunology at the Scripps Clinic and Research Foundation in La Jolla, CA., and the other in the Department of Molecular Microbiology and Immunology at Oregon Health & Science University. Dr. Moses is an Associate Professor at the Vaccine and Gene Therapy Institute. She also holds joint appointments in the Department of Molecular Microbiology and Immunology and the Oregon National Primate Research Center.

Research Overview
My laboratory is interested in viral disease and pathogenesis. We are most interested in human immunodeficiency virus (HIV) the infectious agent responsible for the Acquired Immune Deficiency Syndrome (AIDS), and human herpesvirus-8/Kaposi's sarcoma herpesvirus (HHV8/KSHV), the causative agent of Kaposi's sarcoma (KS), and rare B lymphocyte proliferative diseases.

Our HIV/AIDS research focuses on the viral and cellular mechanisms involved in the development of AIDS-related B cell lymphoma, and the role of the bone marrow in AIDS, both as an HIV reservoir in patients treated with anti-retroviral therapy, and as a site of compromised bone marrow function leading to blood cell dysfunction. We use B cell, macrophage and endothelial cell culture systems to investigate these disease mechanisms. A second focus of the HIV research is the identification of cellular genes as anti-HIV targets. We have used gene profiling to identify cellular genes induced by HIV infection, and are evaluating whether inhibition of cellular gene expression/function inhibits HIV replication.

Our HHV8/KSHV research focuses on determining the virus-induced cellular changes that lead to KS. We have developed a unique cell culture system to study KS pathogenesis and are using this system in parallel with DNA microarray and proteomics technologies. We identified c-Kit as an oncogene essential for KSHV tumorigenesis and are currently evaluating the role of additional cellular and viral genes in vitro and in a mouse model of disease. We anticipate that this approach will be a model for understanding other human cancers and angiogenic processes.

We are also developing systems to infect immune effector cells and endothelial cells with West Nile Virus to enable an in depth collaborative study of WNV immunity and entry to the brain.

Selected References

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. Nat. Med., 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., 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.

Moses, A.V., 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.

Henderson, W.W., 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.

McAllister, S.C., 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.

McAllister, S.C., 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 J. Virol. 79:2626-2630, 2005.

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

Raggo, C., 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.

McAllister, S.C. 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, 2006.

Mansouri, M., 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: 1932-40, 2006.

Rose, P.P., 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. In Press, 2006.