Faculty Profile: Walter Atwood, PHD

Walter Atwood
Walter Atwood, PHD
Professor of Medical Science
Molecular Biology, Cell Biology, & Biochemistry
Work: +1 401-863-3116
Our laboratory is focused on studying the pathogenesis of the human polyomaviruses, JC Virus (JCV) and BK Virus (BKV). Reactivation of JCV under conditions of immunosuppression leads to the fatal demyelinating disease in humans known as Progressive Multifocal Leukoencephalopathy (PML). Approximately 5% of patients with AIDS will develop PML and the majority succumb within two years of diagnosis. Reactivation of BKV in kidney transplant recipients has emerged as a major problem in the last decade and is responsible for nearly half of all kidney transplant failures. The major focus of the lab is studying early events that mediate infection of cells by these viruses.

Biography

B.S. 1986. Microbiology, University of Massachusetts, Amherst
Ph.D. 1991. Neurovirology, University of Massachusetts, Amherst

1991-94 Staff Fellow, Section on Molecular Virology and Genetics, Laboratory of Viral and Molecular Pathogenesis, NINDS, NIH, Bethesda, MD

1992-95 Adjunct Assistant Professor of Microbiology and Immunology, The George Washington University School of Medicine and Health Sciences, Washington, DC

1994-95 Senior Staff Fellow, Section of Molecular Medicine and Virology, Laboratory of Molecular Medicine and Neuroscience, NINDS, NIH, Bethesda, MD

1995-01 Assistant Professor of Medical Science, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI

2001-05 Associate Professor of Medical Science (with Tenure), Department of Molecular Microbiology and Immunology, Brown University, Providence, RI

2005-06 Associate Professor of Medical Science (with Tenure), Department of Molecular Biology, Cell Biology Biochemistry, Brown University, Providence, RI

2006- Professor of Medical Science, Department of Molecular Biology, Cell Biology Biochemistry, Brown University, Providence, RI

Institutions

BU

Research Description

The Laboratory of Molecular Virology at Brown University (Atwood Lab)

Our laboratory is focused on studying the pathogenesis of the human polyomaviruses, JC Virus (JCV) and BK Virus (BKV). Reactivation of JCV under conditions of immunosuppression leads to the fatal demyelinating disease in humans known as Progressive Multifocal Leukoencephalopathy (PML). Approximately 5% of patients with AIDS will develop PML and the majority succumb within two years of diagnosis. Reactivation of BKV in kidney transplant recipients has emerged as a major problem in the last decade and is responsible for nearly half of all kidney transplant failures. The major focus of the lab is studying early events that mediate infection of cells by these viruses. These early events include but are not limited to studies of virus-host cell receptor interactions, endocytic trafficking of virus from the plasma membrane to the nucleus, and virus induced membrane signaling. We have a general interest in studying events that contribute to viral tropism and regulate the balance between infection and resistance. We also focus our efforts at screening lead compounds that block any of these key steps in the viral life cycle as potential therapies to treat or prevent disease caused by JCV and BKV. We approach these problems using state of the art techniques in cell and molecular biology and genetics. Examples of projects of interest are listed below.

Virus-Host Cell Receptor Interactions
• Identify host cell receptors and co-receptors for the human polyomaviruses, JCV and BKV
• Determine the cell and tissue distribution of virus receptors
• Identify factors that increase or decrease virus receptor expression on cells and in tissues
• Identify critical residues in the viral capsid that mediates binding to virus receptors

Cell Biology
• Define the role of the cytoskeleton in trafficking of virus from the plasma membrane to the nucleus
• Determine the mechanism by which JCV and BKV deliver their respective genomes across the nuclear membrane
• Identify the site and mechanism of virus uncoating

Molecular Biology
• Characterize molecular signals induced upon virus binding to host cell surfaces
• Characterize downstream signal transduction events and define how they impact viral infection
• Define the cellular and viral determinants that mediate signaling

Genetics and Genomics
• Identify host cell genes that are turned on or off in response to viral infection
• Identify genes that are differentially expressed in cells that are resistant to JCV infection versus cells that are susceptible to infection

Molecular Medicine
• Identify compounds capable of preventing the establishment of viral infection in host cells and interfering with the replication and growth of human polyomaviruses
• Identify risk factors for the development of PML in HIV infected and other immunosuppressed patient populations
• Identify risk factors for the development of BKV associated nephropathy in kidney transplant recipients

Grants and Awards

Editorial Board Member, Journal of Virology
National Institutes of Health Virology Study Section Member
Master of Arts Ad Eundem, Brown University
Dean's Teaching Excellence Award, Brown Medical School

Affiliations

American Association for the Advancement of Science
American Society of Microbiology
Sigma Xi
American Society for Virology
International Society for NeuroVirology (Founding Member)
American Society for Cell Biology

Funded Research

National Institutes of Health Grant # P01 NS065719; "Structure-function based development of JC vision specific antagonists for PML"; 09/30/09-07/31/14; Principal Investigator: W. J. Atwood

National Institutes of Health Grant # R01-NS43097; "Virus-Host Cell Interactions in AIDS-Associated PML"; 12/15/01-06/30/16; Principal Investigator: W. J. Atwood

National Institutes of Health Grant # P30 GM103410; "Center for Cancer Signaling Networks"; 04/15/11-03/31/16; Principal Investigator: W.J. Atwood

Teaching Experience

Molecular Virology

Courses Taught

  • Graduate Independent Study (BI0293)
  • Independent Research (BI0195)
  • Medical Microbiology (BI0158)
  • Virology (BI0156)

Selected Publications

  • Seo, G.J., Fink, L.H., O'Hara, B., Atwood, W.J., and C.S. Sullivan. 2008.Evolutionarily conserved function of a viral microRNA. J. Virol. 82:9823-9828. (2008)
  • Schaumburg, C., O'Hara, B.A., Lane, T., and W.J. Atwood. 2008. Humanembryonic stem cell-derived oligodendrocyte progenitor cells express theserotonin receptor and are susceptible to JC Virus infection. J. Virol. 82: 8896-8899. (2008)
  • Dugan, A.S., Gasparovic, M.L., and W.J. Atwood. 2008. Direct correlation between sialic acid binding and infection of cells by human polyomaviruses. J.Virol. 82:2560-2564. (2008)
  • Dugan A.S., Maginnis, M.S., Jordan, J.A., Gasparovic, M.L., Manley, K., Page,R., Williams, G., Porter, E., O'Hara, B.A., and W.J. Atwood. 2008. Human alphadefensins inhibit BK virus infection by aggregating virions and blocking binding to host cells. J. Biol. Chem. 283: 31125-31132. (2008)
  • Dugan, A.S., Gasparovic, M.L., Tsomaia, N., Mireke, D.F., O'Hara, B.A., Manley,K., and W.J. Atwood. 2007. Identification of amino acid residues in BK virus VP1critical for viability and growth. J. Virol. 81:11798-11808. (2007)
  • Manley, K., Gee, G.V., Simkevich, C.P., Sedivy, J.M., and W.J. Atwood. 2007.Microarray analysis of glial cells resistant to JCV infection suggests a correlation between viral infection and inflammatory cytokine gene expression. Virology 366:394-404 (2007)
  • Manley, K., O'Hara, B. A., Gee, G.V., Simkevich, C.P., Sedivy, J.M., and W.J.Atwood. 2006. NFAT4 is required for JCV infection of glial cells. J. Virol.80:12079-12085. (2006)
  • Querbes, W., O'Hara, B.A., Williams, G., and W.J. Atwood. 2006. Invasion of host cells by JC virus identifies a novel role for caveolae in endosomal sorting of non-caveolar ligands. J. Virol. 80:9402-9413. (2006)
  • Eash, S., Manley, K., Gasparovic, M., Querbes, W., and W.J. Atwood. 2006. The human polyomaviruses. Cell Mol. Life Sci. 63:865-876. (2006)
  • Josephson, M.A., Gillen, D., Javaid, B., Kadambi, P., Meehan, S., Foster, P.,Harland, R., Garfinkel, M., Atwood, W., Jordon, J., Sadhu, M., Millis, M.J., and Williams, J. 2006. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation 81:704-710. (2006)
  • Gasparovic, K.L., Gee, G.V., and W.J. Atwood. 2006. The JC Virus (JCV) minor capsid proteins VP2 and VP3 are essential for virus propagation. J. Virol.80:10858-10861. (2006)
  • Dugan, A.S., Eash, S., and W.J. Atwood. 2005. A N-linked Glycoprotein with α(2,3)-Linked Sialic Acid is a Receptor for BK Virus. J. Virol. 79:14442-14445. (2005)
  • Williams J., Javaid, B., Kadambi, P., Meehan, S., Foster, P., Harland, R.,Thistlethwaite, R., Garfinkel, M., Atwood, W., Sadhu, A., Gillen, D., Millis, M., and M. Josephson. 2005. Leflunomide for Polyomavirus Type BK Nephropathy.NEJM 352:1157-1158. (2005)
  • Eash, S., and W.J. Atwood. 2005. Involvement of cytoskeletal components inBKV infectious entry. J. Virol. 79:11734-11741. (2005)
  • Gee, G.V., Tsomaia, N., Mierke, D., and W.J. Atwood. 2004. Modeling a sialic acid binding pocket in the external loops of JCV VP1. J. Biol. Chem.279(47):49172-6. (2004)
  • Eash, S., Querbes, W., and W.J. Atwood. 2004. Infection of Vero cells by BK Virus (BKV) is caveolae dependent. J. Virol. 78:11583-11590. (2004)
  • Trophe, J., Gordon, J., Roy-Chaudhury, P., Koralnik, I., Atwood, W.J., Alloway,R.R., Khalili, K., and E. S. Woodle. 2004. Polyomavirus nephropathy in kidney transplantation. Progress in Transplantation 14:130-142. (2004)
  • Qu, Q., Sawa, H., Suzuki, T., Semba, S., Henmi, C., Okada, Y., Tsuda, M.,Tanaka, S., Atwood, W.J., and K. Nagashima. 2004. Nuclear entry mechanism of the human Polyomavirus JC virus like particle: role of importins and the nuclear pore complex. J. Biol. Chem. 279:27735-42 . (2004)
  • Querbes, W., Benmerah, A., Tosoni, D., Di Fiore, P.P., and W.J. Atwood. 2004. A JC virus induced signal is required for infection of glial cells by a clathrin and eps15 dependent pathway. J. Virol. 78: 250-256. (2004)
  • Eash, S., Tavares, R., Stopa, E.G., Robbins, S., Brossay, L., and W.J. Atwood.2004. Differential distribution of the JC virus receptor-type sialic acid in normal human tissues. Am. J. Pathol. 164:419-428. (2004)
  • Trophe, J., Gordon, J., Roy-Chaudhury, P., Koralnik, I., Atwood, W.J., Eash S.,Alloway, R.R., Khalili, K., Alexander, J.W. and E. S. Woodle. 2004. Basic and Clinical Research in Polyomavirus Nephropathy. Experimental and Clinical Transplantation 2:162-173. (2004)
  • Elphick, G.F., Querbes, W., Jordan, J.A., Gee, G.V., Eash, S., Manley, K.,Dugan, A., Stanifer, M., Roth, B.L., and W.J. Atwood. 2004. The human polyomavirus, JCV, uses serotonin receptors to infect cells. Science 306:1380-1384. (2004)
  • Gee, G., Manley, K., and W.J. Atwood. 2003. Derivation of a JC virus resistant cell line: Implications for the identification of host cell factors that determine viral tropism. Virology 314:101-109. (2003)
  • Komagome. R., Sawa, H., Suzuki, Y., Tanaka, S., Atwood, W.J., and K.Nagashima. 2002. Oligosaccharides as receptors for JC Virus. J. Virol.76:12992-13000. (2002)
  • Chen, B.J., and W.J. Atwood. 2002. Construction of a novel JCV/SV40 hybrid virus reveals a role for the JCV capsid in viral tropism. Virology 300:282-290. (2002)
  • Ashok, A., and W.J. Atwood. 2003. Contrasting roles of endosomal pH and thecytoskeleton in infection of human glial cells by JC Virus and SV40. 2002. J.Virol.77:1347-1356. (2002)
  • Schweighardt, B., Shieh, J.T., and W.J. Atwood., 2001. CD4/CXCR4independent infection of human astrocytes by a T-tropic strain of HIV-1. J.Neurovirol. 7 (2):155-162. (2001)
  • Schweighardt, B., and W.J. Atwood. 2001. HIV-1 infection of human astrocytes is restricted by inefficient viral entry. AIDS Research and Human Retroviruses 17(12): 1133-1142. (2001)
  • Pho, M.T., Ashok, A., and W.J. Atwood., 2000. JC Virus enters human cells by clathrin dependent receptor mediated endocytosis. J. Virol. J. 74:2288-2292. (2000)
  • Wei, G.W., Liu, C.K., and W.J. Atwood.,2000. JC Virus binds to primary human glial cells,tonsillar stromal cells, and B-lymphocytes, but not to T-lymphocytes. J.Neurovirol. 6:127-136. (2000)
  • Liu, C.K., Hope, A.P., and W.J. Atwood. 1998. The human polyomavirus, JCV,does not share receptor specificity with SV40 on human glial cells. J. Neurovirol.4:49-58. (1998)
  • Liu, C.K., Wei, G., and W.J. Atwood. 1998. Infection of glial cells by the human polyomavirus, JCV, is mediated by a N-linked glycoprotein containing terminal α(2-6) linked sialic acids. J. Virol. 72:4643-4649. (1998)
  • Tornatore, C., Baker-Cairns, B., Yadid, G., Hamilton, R., Meyers, K., Atwood, W.,Cummins, A., Cheng, S., Tanner, V., and E. Major. 1996. Expression of tyrosine hydroxylase in an immortalized human fetal astrocyte cell line; In vitrocharacterization and engraftment into the rodent striatum. Cell Transplantation.5:145-163. (1996)
  • Monaco, M.C.G., Atwood, W.J., Gravell, M., Tornatore, C.S., and E.O.Major.1996. JCV infection of hematopoietic progenitor cells, primary B lymphocytes and tonsillar stromal cells: implication for viral latency. J. Virol. 70:7004-7012. (1996)
  • Atwood, W.J., Wang, L., Durham, L.C., Amemiya, K., Traub, R.G., and E.O.1995. Major. Evaluation of the role of cytokine activation in the multiplication of JC Virus (JCV) in human fetal glial cells. J. Neurovirol. 1:40-49. (1995)
  • Conant, K., Atwood, W.J., Traub, R., Tornatore, C.S., and E.O. Major.1994. Expression of HIV-1 in human fetal astrocytes: Role of PKC and NFkB. Virology 205:586-590. (1994)
  • Atwood, W.J., Tornatore, C., Traub, R., Conant, K., Drew, P., and E.O.Major.1994. Stimulation of HIV-1 gene expression and induction of NFkB (p50/p65) in TNF-α treated human fetal glial cells. AIDS Research and Human Retroviruses.10:1207-1211. (1994)
  • Tornatore, C.S., Meyers, K., Atwood, W.J., Conant, K., and E.O. Major. 1994.Temporal characterization of HIV-1 mRNA transcripts from persistently infected human fetal astrocytes. J. Virol. 68:93-102. (1994)
  • Atwood, W.J., Tornatore, C., Meyers, K., and E.O. Major. 1993. HIV-1 mRNA transcripts from persistently infected human fetal astrocytes. Ann. New York Acad. Sci. 693:323-324. (1993)
  • Atwood, W.J., Berger, J., Kaderman, R., Tornatore, C.S., and E.O. Major. 1993.HIV-1 infection of the central nervous system. Clin. Microbiol. Rev. 6:339-366. (1993)
  • Atwood, W.J., Amemiya, K., Traub, R., Harms, J. and E.O. Major. 1992.Interaction of the human polyomavirus, JCV, with human B-lymphocytes.Virology 190:716-723. (1992)
  • Breau, W., Atwood, W.J. and L.C. Norkin. 1992. Class I major histocompatibility complex proteins are an essential component of the SV40 receptor. Journal of Virology 66:2037-2045. (1992)