William A. O'Brien, III, M.D., M.S.

"Our laboratory has a broad-based program to investigate the
pathogenesis of HIV infection. Our specific focus is on the
mechanism of viral entry and cellular tropism, the mechanism
of HIV-related neurologic disease, and molecular
determinants of resistance to antiviral drugs."

Curriculum vitae

Title and Photograph	Position and Address	Education
Professional and Teaching Experience	Research Interests	Current Research Funding
Editorial Activities	Manuscript Activities	Bibliography

Professor of Internal Medicine, Pathology and Microbiology and Immunology
Chief, AIDS Pathogenesis Research Program
Chief, AIDS Clinical Trial Unit, ACTG
Division of Infectious Diseases
Department of Internal Medicine
University of Texas Medical Branch
301 University Boulevard, Rte. 0435
Galveston, TX 77555-0435

Phone: (409) 747-2361
FAX: (409) 747-0507
E-mail: wobrien@utmb.edu

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Education:

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Professional and Teaching Experience:

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Research Interests:

My laboratory is involved in investigation of viral pathogenesis, especially for HIV, but in new projects, also for Hepatitis C virus (HCV). A principle focus of the laboratory has been the mechanism of viral entry, in particular the molecular determinants of envelope interactions responsible for efficient virus entry. We are currently exploring coreceptor utilization by HIV, based on studies demonstration that a second interaction involving chemokine receptors is required for efficient viral entry following CD4 binding. We are also exploring mechanisms of virus entry, including post-receptor binding cellular interactions and fusion. The effect of envelope or products from infected cells on cell death and cell dysfunction both in the periphery and in the central nervous system is another focus of our studies. In addition to these molecular lab-based studies, we are also investigating use of molecular markers of HIV infection in clinical practice. These include viral load measurements of both HIV-specific RNA and DNA in both peripheral blood and in lymphoid tissue, as well as molecular assays to assess antiretroviral drug resistance.

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Current Research Funding:

NIH/NIAID R21 (PI) HIV Macrophage Tropism
NIH RO1 (Co-I) HIV associated peripheral neuropathy
NIH/NINDS RO1 (PI), Lipid mediators in HIV neurotransmitter dysfunction
NIH/NINDS R24 (CO-I), Texas repository for AIDS neuropathogenesis research
NIH RO1 (Co-I) CD8+ T-Cell Apoptosis in HIV Infection
NIH/NIDA RO1 (PI) Predictors of adherence in HIV+ cocaine abusers

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Editorial Activities:

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Manuscript Reviewer:

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Bibliography:

Articles in Peer-reviewed Journals:

1. Baker RM, O'Brien WA, III, Hirschberg C, Spencer LA, Awerbuch T, Weisman TO: Selection of CHO cells with reduced carbohydrate incorporation by means of 3H-Mannose suicide. J Cell Biol 83:453-459, 1979.

2. Baker RM, Hirschberg, CB, O'Brien WA, III, Awerbuch TE, Watson D: Isolation of somatic cell glycoprotein mutants. Methods Enzymol 83:444-458, 1982.

3. Mulligan ME, Ruane RJ, Johnston L, Wong P, Wheelock JP, MacDonald K, Reinhardt JF, Johnson CC, Statner B, Blomquist I, McCarthy J, O'Brien WA, Gardner S, Hammer L, Citron DM: Ciprofloxacin for eradication of Methicillin-resistant Staphylococcus aureus colonization. Am J Med 82:215-219, 1987.

4. Koyanagi Y, O'Brien WA, Zhao JQ, Golde DW, Gasson JC, Chen ISY: Cytokines alter production of HIV from primary mononuclear phagocytes. Science 241:1673-1675, 1988.

5. O'Brien WA, Koyanagi Y, Namazie A, Zhao J-Q, Diagne A, Idler K, Zack JA, Chen ISY: HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp 120 outside the CD4-binding domain. Nature 348:69-73, 1990.

6. Chesebro B, Nishio J, Perryman S, Cann A, O'Brien W, Chen ISY, Wehrly K: Identification of HIV envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-cell leukemia cells and macrophages. J Virol 65:5782-5789, 1991.

7. Pang S, Vinters HV, Akashi T, O'Brien WA, Chen ISY: HIV-1 Env sequence variation in brain tissue of patients with AIDS encephalopathy. J Acquir Immun Defic Syndrome 4:1082-1091, 1991.

8. Rich EA, Chen ISY, Zack JA, Leonard ML, O'Brien WA: Increased susceptibility of differentiated mononuclear phagocytes to productive infection with human immunodeficiency virus type 1 (HIV-1). J Clin Invest 89:176-183, 1992.

9. Cann AJ, Churcher MJ, Boyd M, O'Brien WA, Zhao J-Q, Zack JA, Chen ISY: The region of the envelope gene of HIV-1 responsible for determination of cell tropism. J Virol 66:305-309, 1992.

10. Hamilton JD, Hartigan PM, Simberkoff MS, Day PL, Diamond GR, Dickinson GM, Drusano GL, Egorin MJ, George WL, Gordin FM, Hawkes CA, Jensen PC, Klimas NG, Labriola AM, Lahart CJ, O'Brien WA, Oster CN, Weinhold KJ, Wray NP, Ziegler JL, Zolla-Pazner SB, VA Cooperative Study Group on AIDS Treatment: Early versus later zidovudine therapy for patients with symptomatic human immunodeficiency virus infection: Results of a randomized, double-blind VA cooperative study. New Engl J Med 326:437-443, 1992.

11. Sharpless NE, O'Brien WA, Verdin EM, Kufta CV, Chen ISY, Dubois-Dalcq M: A primary determinant of immunodeficiency virus 1 (HIV-1) neurotropism resides in a region of the env glycoprotein that also controls monocyte-macrophage tropism. J Virol 66:2588-2593, 1992.

12. O'Brien WA, Chen ISY, Ho DD, Daar ES: HIV-1 resistance to soluble CD4 is conferred by domains of gp 120 that determine cell tropism. J Virol 66:3125-3130, 1992.

13. O'Brien WA: Viral determinants of cellular tropism. Pathobiology 60:225-233, 1992.

14. Sevall JS, Prince H, Garraty G, O'Brien WA, Zack JA: Rapid enzymatic analysis for HIV-1 DNA in clinical specimens. Clin Chem 39:433-439, 1993.

15. St. Clair MH, Hartigan, PM, Andrews JC, Vavro CL, Simberkoff MS, Hamilton JD, VA Cooperative Study Group: Zidovudine resistance, syncytium-inducing phenotype, and HIV disease progression in a case-control study. J AIDS 6:891-897, 1993.

16. O'Brien WA, Namazi A, Mao S-H, Kalhor H, Zack JA, Chen ISY: Kinetics of HIV-1 reverse transcription in blood mononuclear phagocytes are slowed by limitations of nucleotide precursors. J Virol 68:1258-1263, 1994.

17. O'Brien WA, Mao S-H, Cao Y, Moore JP: Macrophage and T-cell tropic HIV-1 strains differ in their susceptibility to neutralization by soluble CD4 at different temperatures. J Virol 68:5264-5269, 1994.

18. O'Brien WA: HIV-1 entry and reverse transcription in macrophages. J Leuk Biol 56:273-277, 1994.

19. Yu X, McLane MF, Ratner L, O'Brien WA, Collman R, Essex M, Lee T-H: Direct killing of primary CD4+ T-cells by HIV-1. Proc Natl Acad Sci, USA 91:10237-10241, 1994.

20. O'Brien WA, Grovit-Ferbas K, Namazi A, Ovcak-Derzic S, Wang H-J, Park J, Yeramian C, Mao S-H, Zack JA: HIV-1 replication can be increased in peripheral blood of seropositive patients following influenza immunization. Blood 86:1082-1089, 1995.

21. O'Brien WA, Hartigan PM, Martin D, Esinhart J, Hill A, Benoit S, Rubin M, Simberkoff MS, Hamilton JD: Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. New Engl J Med 334:426-431, 1996.

22. Simberkoff MS, Hartigan PM, Hamilton JD, Day PL, Diamond GR, Dickinson GM, Drusano GL, Egorin MJ, George WL, Gordin FM, Hawkes CA, Jensen PC, Klimas NG, Labriola AM, Lahart CJ, O'Brien WA, Oster CN, Weinhold KJ, Wray NP, Zolla-Pazner SB, and the VA Cooperative Study Group on AIDS Treatment. Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment: Report of a Veterans Affairs Cooperative Study. J Aquir Immun Defic Syndrome 11:142-150, 1996.

23. O'Brien WA, Sumner-Smith M, Mao S-H, Sadeghi S, Zhao J-Q, Chen ISY: Anti-HIV-1 activity of an oligocationic compound is mediated via gp120 V3 interactions. J Virol 70:2825-2831, 1996.

24. Saag MS, Holodniy M, Kuritzkes DR, O'Brien WA, Coombs RW, Poscher ME, Jacobsen DM, Shaw GM, Richman DD, Volberding PA: HIV viral load markers in clinical practice. Nature Medicine 2:625-629, 1996.

25. Mudido PM, Georges D, Dorazio D, Yen-Lieberman B, Bae S, O'Brien WA, Spritzler J, Lederman MM: HIV-1 activation after blood transfusion. Tranfusion 36:860-865, 1996.

26. O'Brien WA: Vaccinations for patients with HIV: Weighing risks and benefits. HIV. Advances in Research and Therapy 6:22-27, 1996.

27. O'Brien WA, Hartigan PM, Daar ES, Simberkoff MS, Hamilton JD: Use of Plasma HIV RNA and CD4 Lymphocyte Count to Direct Antiretroviral Drug Treatment. Ann Intern Med 126: 939-945, 1997.

28. Doranz BJ, Grovit-Ferbas K, Goetz MB, Daar ES, Doms RW, O'Brien WA. A small molecule inhibitor directed against the chemokine receptor CXCR4 prevents its use as an HIV-1 coreceptor. J Exp Med 186:1-6, 1997.

29. Nimmagadda A, O’Brien WA, Goetz MB. Prevalence and significance of hypo-retinemia in persons infected by the Human Immunodeficiency Virus. Clin Infect Dis 26:711-8, 1998.\

30. Arnó A, Ruiz L, Juan M, Zayat MK, Puig T, Balagué M, Romeu J, Pujol R, O´Brien WA, Clotet B: Impact on the immune system of undetectable plasma HIV-1 RNA (<20 copies/ml) for more than 2 years. AIDS 12:697-704, 1998.
    
31. Tasker SA, O'Brien WA, Treanor JJ, Weiss PJ, Olson PE, Kaplan AH, and Wallace MR. Effects of influenza vaccination in HIV-infected adults: a double-blind, placebo-controlled trial. Vaccine 16:1039-1042, 1998.
    

32. Stringer WW, Berezovskaya M, O'Brien WA, Beck CK, Casaburi R: The effect of exercise training on aerobic fitness, immune function, and quality of life of HIV Patients. A randomized, controlled trial. Medicine, Science, Sports and Exercise 30:11-16, 1998.

33. Herbein G, Mahlknecht U, Batliwalla F, Gregersen PK, Pappas T, Butler J, O'Brien WA, and Verdin E. Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4. Nature 395:189-194, 1998.

34. Grovit-Ferbas K, V Chen ISY, Ferbas J, Gudeman V, Giorgi JV, O'Brien WA. Potential contributions of viral envelope and host genetic factors in an HIV-1 longterm survivor. J Virol 72: 8650-8658, 1998.

35. Nimmagadda AP, Burri BJ, Neidlinger T, O'Brien WA, Goetz MB. Effect of oral ß-carotene supplementation on plasma HIV RNA and CD4+ cell counts in HIV-infected patients. Clin Infect Dis 27:1311-3, 1998.

36. Fehniger TA, Herbein G, Yu H, Para MI, Berstein ZP, O'Brien WA, and Caligiuri MA. Natural killer cells from HIV-1+ patients produce C-C chemokine and inhibit HIV-1 infection. J Immunol 161:6433-6438, 1998.

37. Suzuki Y, Koyanagi Y, Yuetsu T, Murakami T, Misawa N, Kimura T, Hoxie JA, O'Brien WA, and Yamamoto N. Type 1 helper cell (Th1) and Th2 preferences of human immunodeficiency virus type 1. J Virol 73: 316-324, 1999.

38. Garcia F, Plana M, Vidal C, Cruceta A, O'Brien WA, Miró JM, Pumarola T, Gallart T, Gatell JM, on behalf of Microbiology and Immunology group of the Spanish Earth Study. Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy. AIDS 13(11):F79-86, 1999.

39. Garcia F, Romeau J, Grau I, Sambeat MA, Dalmau D, Knobel H, Gomez-Sirvent JL, Arrizabalaga J, Cruceta A, Clotet BG, Podzamczer D, Pumarola T, Gallart T, O'Brien WA, Miro JM, Gatel JM. A randomized study comparing triple versus double antiretroviral therapy or no treatment in HIV-1 infected patients in very early stage disease: the Spanish Earth-1 study. AIDS 139(7):2377-88, 1999.

40. Herbein G and O'Brien WA. Tumor necrosis factor ( (TNF) and TNF receptors in viral pathogenesis. Proc Soc Exper Biol Med 223:241-257, 2000.

Other:

Research Papers--Non-peer Reviewed:

41. Mulligan ME, Ruane RJ, Johnston L, Wong P, Wheelock JP, MacDonald K, Reinhardt JF, Johnson CC, Statner B, Blomquist I, McCarthy J, O'Brien W, Gardner S, Hammer L, Citron DM: Ciprofloxacin for eradication of Methicillin-resistant Staphylococcus aureus colonization. Am J Med 82:215-219, 1987.

42. O'Brien WA, Guze PA: An approach to AIDS in the Emergency Department. Hosp Phys 23:37-41, 1987.

43. O'Brien WA, Johnson V, Holodniy M: Plasma HIV RNA monitoring in clinical practice, results of a roundtable discussion, Comprehensive Management of HIV Disease, Sixth Annual Update, 1996.

44. Butler J, O'Brien WA: Treatment with Protease inhibitors during disseminated tuberculosis. HIV Clinical Lesson 3:2-5, 1997.

Book Chapters:

45. O'Brien WA, Koyanagi Y, Chen ISY: Virologic aspects of AIDS and the nervous system, in Neuropathology of AIDS, Vinters HV, Anders KH (eds). CRC Press, Philadelphia PA, 1990, pp. 189-207.

46. O'Brien WA, Zack JA, Chen ISY: Molecular pathogenesis of HIV-1. In: AIDS 1990 - A Year in Review, Goudsmit J, Martin M (eds). Current Science Ltd, London UK, 1991, pp. S41-S48.

47. O'Brien WA: Genetic and biologic basis of HIV-1 neurotropism. In: HIV, AIDS and the Brain. Price RW, Perry SW (eds) Raven Press, New York, NY, 1994, pp. 47-70.

48. O'Brien WA and Pomerantz RJ: AIDS and other diseases due to HIV infection. In: Viral Pathogenesis. Nathanson N (ed) Raven Press, New York, NY, 1997, pp 815-836.

49. Stevenson M and O'Brien WA: The Molecular Biology of HIV-1: Relationships to Neuro Tropism and Neuro Virulence. In: Neurological and Neuropsychiatric Manifestations of HIV-1 Infection, Gendeleman HE, Lipton S, Epstein L, Swindells S, (eds). Chapman and Hall, New York, NY, 1998, pp. 13-35.

50. Grovit-Ferbas, Pappas T, and O'Brien WA: Human immunodeficiency viruses. In: Persistent Viral Infections, Chen ISY and Ahmed R (eds) John Wiley & Sons, New York, NY, 1999, pp. 3-46.

Reviews:

51. O'Brien WA: "Review of AIDS and Other Manifestations of HIV Infection." Wormser GP (ed) 2nd ed. Raven Press, New York, NY. In: Clinical Infectious Disease 17: 1088, 1993.

Research Papers--Peer Reviewed (in press):

52. O'Brien WA. Reverse transcriptase inhibitor resistance. Clin Infect Dis, 2000 in press.

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