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
1: 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. PMCID: PMC3340234

2: Sugaya M, Reed S, Rose PP, de la Motte S, Raggo CM, Kurtz SE, Moses AV, Früh K, Blauvelt A. Kaposi's sarcoma and human dermal microvascular endothelial cells infected with Kaposi's sarcoma-associated herpesvirus express CCL21. J Dermatol Sci. 2011 Feb; 61(2): 139-42. PMCID: PMC3399906

3: Gustin JK, Moses AV, Früh K, Douglas JL. Viral takeover of the host ubiquitin system. Front Microbiol. 2011; 2: 161. PMCID: PMC3147166

4: Douglas JL, Gustin JK, Viswanathan K, Mansouri M, Moses AV, Früh K. The great escape: viral strategies to counter BST-2/tetherin. PLoS Pathog. 2010 May 13; 6(5): e1000913. Review. PMCID: PMC2869331

5. Douglas J. L., J. K. Gustin, A. V. Moses, B. J. Dezube, and L Pantanowitz.   Kaposi Sarcoma pathogenesis:  a triad of viral infection, oncogenesis, and chronic inflammation. Transl Biomed  2010 1(2): 1-15. PMCID: PMC3472629

6: Pantanowitz L, Moses AV, Dezube BJ. The inflammatory component of Kaposi’s sarcoma. Exp Mol Pathol. 2009 Oct; 87(2): 163-5. Review. PMID: 19591823 

7: Mansouri M, Viswanathan K, Douglas JL, Hines J, Gustin J, Moses AV, Früh K. Molecular mechanism of BST2/tetherin downregulation by K5/MIR2 of Kaposi's sarcoma-associated herpesvirus. J Virol. 2009 Oct; 83(19): 9672-81. PMCID: PMC2748026

8: Douglas JL, Viswanathan K, McCarroll MN, Gustin JK, Früh K, Moses AV. Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a {beta}TrCP-dependent mechanism. J Virol. 2009 Aug; 83(16): 7931-47. PMCID: PMC2715753

9: Douglas JL, Whitford JG, Moses AV. Characterization of c-Kit expression and activation in KSHV-infected endothelial cells. Virology. 2009 Aug 1; 390(2): 174-85. PMCID: PMC3489927

10: Mansouri M, Rose PP, Moses AV, Früh K. Remodeling of endothelial adherens junctions by Kaposi's sarcoma-associated herpesvirus. J Virol. 2008 Oct; 82(19): 9615-28. PMCID: PMC2546942

11: Pantanowitz L, Früh K, Marconi S, Moses AV, Dezube BJ. Pathology of rituximab-induced Kaposi sarcoma flare. BMC Clin Pathol. 2008 Jul 23; 8: 7. PMCID: PMC2515841

12: Dumortier J, Streblow DN, Moses AV, Jacobs JM, Kreklywich CN, Camp D, Smith RD, Orloff SL, Nelson JA. Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing. J Virol. 2008 Jul; 82(13): 6524-35. PMCID: PMC2447085

12: Rose PP, Bogyo M, Moses AV, Früh K. Insulin-like growth factor II receptor-mediated intracellular retention of cathepsin B is essential for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus. J Virol. 2007 Aug; 81(15): 8050-62. PMCID: PMC1951299

13: Mansouri M, Douglas J, Rose PP, Gouveia K, Thomas G, Means RE, Moses AV, Früh K. Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells. Blood. 2006 Sep 15; 108(6): 1932-40. PMCID: PMC1635550

14: Raggo C, Ruhl R, McAllister S, Koon H, Dezube BJ, Früh K, Moses AV. Novel cellular genes essential for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus. Cancer Res. 2005 Jun 15; 65(12): 5084-95. PMID: 15958552  

15: McAllister SC, Früh K, Moses AV. Functional genomics and the development of pathogenesis-targeted therapies for Kaposi's sarcoma. Pharmacogenomics. 2005 Apr; 6(3): 235-44. Review. PMID: 16013955

16: McAllister SC, Hansen SG, Messaoudi I, Nikolich-Zugich J, Moses AV. Increased efficiency of phorbol ester-induced lytic reactivation of Kaposi's sarcoma-associated herpesvirus during S phase. J Virol. 2005 Feb; 79(4): 2626-30. PMCID: PMC546546

17: McAllister SC, Hansen SG, Ruhl RA, Raggo CM, DeFilippis VR, Greenspan D, Früh K, Moses AV. Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells. Blood. 2004 May 1; 103(9): 3465-73. PMID: 14726403

18: Henderson WW, Ruhl R, Lewis P, Bentley M, Nelson JA, Moses AV. Human immunodeficiency virus (HIV) type 1 Vpu induces the expression of CD40 in endothelial cells and regulates HIV-induced adhesion of B-lymphoma cells. J Virol. 2004 May; 78(9): 4408-20. PMCID: PMC387678

19: Ancuta P, Moses AV, Gabuzda D. Transendothelial migration of CD16+ monocytes in response to fractalkine under constitutive and inflammatory conditions. Immunobiology. 2004; 209(1-2): 11-20. PMID: 15481136

20: DeFilippis V, Raggo C, Moses AV, Früh K. Functional genomics in virology and antiviral drug discovery. Trends Biotechnol. 2003 Oct; 21(10): 452-7. Review. PMID: 14512232

21: Ancuta P, Rao R, Moses AV, Mehle A, Shaw SK, Luscinskas FW, Gabuzda D. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes. J Exp Med. 2003 Jun 16; 197(12): 1701-7. PMCID: PMC2193954

22: Moses AV, Jarvis MA, Raggo C, Bell YC, Ruhl R, Luukkonen BG, Griffith DJ, Wait CL, Druker BJ, Heinrich MC, Nelson JA, Fruh K. A functional genomics approach to Kaposi's sarcoma. Ann N Y Acad Sci. 2002 Dec; 975: 180-91. PMID: 12538164

23: Moses AV, Jarvis MA, Raggo C, Bell YC, Ruhl R, Luukkonen BG, Griffith DJ, Wait CL, Druker BJ, Heinrich MC, Nelson JA, Früh K. Kaposi's sarcoma-associated herpesvirus-induced upregulation of the c-kit proto-oncogene, as identified by gene expression profiling, is essential for the transformation of endothelial cells. J Virol. 2002 Aug; 76(16): 8383-99. PMCID: PMC155158

24: Moses AV, Jarvis MA, Raggo C, Bell YC, Ruhl R, Luukkonen BG, Griffith DJ, Wait CL, Druker BJ, Heinrich MC, Nelson JA, Fruh K. A functional genomics approach to Kaposi's sarcoma. Ann N Y Acad Sci. 2002 Dec; 975: 180-91. PMID: 12538164

25: Moses AV, Jarvis MA, Raggo C, Bell YC, Ruhl R, Luukkonen BG, Griffith DJ, Wait CL, Druker BJ, Heinrich MC, Nelson JA, Früh K. Kaposi's sarcoma-associated
herpesvirus-induced upregulation of the c-kit proto-oncogene, as identified by gene expression profiling, is essential for the transformation of endothelial cells. J Virol. 2002 Aug; 76(16): 8383-99. PMCID: PMC155158

26: Zoeteweij JP, Moses AV, Rinderknecht AS, Davis DA, Overwijk WW, Yarchoan R, Orenstein JM, Blauvelt A. Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus. Blood. 2001 Apr 15; 97(8): 2374-80. PMID: 11290600

27: Dallasta LM, Pisarov LA, Esplen JE, Werley JV, Moses AV, Nelson JA, Achim CL. Blood-brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. Am J Pathol. 1999 Dec; 155(6): 1915-27. PMCID: PMC1866950

28: Moses AV, Fish KN, Ruhl R, Smith PP, Strussenberg JG, Zhu L, Chandran B, Nelson JA. Long-term infection and transformation of dermal microvascular endothelial cells by human herpesvirus 8. J Virol. 1999 Aug; 73(8): 6892-902. PMCID: PMC112774

29: Moses AV, Williams SE, Strussenberg JG, Heneveld ML, Ruhl RA, Bakke AC, Bagby GC, Nelson JA. HIV-1 induction of CD40 on endothelial cells promotes the outgrowth of AIDS-associated B-cell lymphomas. Nat Med. 1997 Nov; 3(11): 1242-9. PMID: 9359699

30: Prudhomme JG, Sherman IW, Land KM, Moses AV, Stenglein S, Nelson JA. Studies of Plasmodium falciparum cytoadherence using immortalized human brain capillary endothelial cells. Int J Parasitol. 1996 Jun; 26(6): 647-55. PMID: 8875310

31: Moses AV, Stenglein SG, Strussenberg JG, Wehrly K, Chesebro B, Nelson JA. Sequences regulating tropism of human immunodeficiency virus type 1 for brain capillary endothelial cells map to a unique region on the viral genome. J Virol. 1996 Jun; 70(6): 3401-6. PMCID: PMC190212

32: Moses AV, Williams S, Heneveld ML, Strussenberg J, Rarick M, Loveless M, Bagby G, Nelson JA. Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors. Blood. 1996 Feb 1; 87(3): 919-25. PMID: 8562963

33: Moses AV, Stenglein SG, Nelson JA. HIV infection of the brain microvasculature and its contribution to the AIDS dementia complex. J NeuroAIDS.  1996; 1(1): 85-99. Review. PMID: 16873156

34: Fish KN, Depto AS, Moses AV, Britt W, Nelson JA. Growth kinetics of human cytomegalovirus are altered in monocyte-derived macrophages. J Virol. 1995 Jun; 69(6): 3737-43. PMCID: PMC189090

35: Moses AV, Nelson JA. HIV infection of human brain capillary endothelial cells--implications for AIDS dementia. Adv Neuroimmunol. 1994; 4(3): 239-47. Review. PMID: 7533040

36: Moses AV, Ibanez C, Gaynor R, Ghazal P, Nelson JA. 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. 1994 Jan; 68(1): 298-307. PMCID: PMC236289

37: Moses AV, Bloom FE, Pauza CD, Nelson JA. Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism. Proc Natl Acad Sci U S A. 1993 Nov 15; 90(22): 10474-8. PMCID: PMC47799

38: Moses AV, Garnett HM. The effect of human cytomegalovirus on the production and biologic action of interleukin-1. J Infect Dis. 1990 Aug; 162(2): 381-8. PMID: 2165111