Wong, Paul K.Y.

Wong, Paul K.Y. Ph.D.

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Research Interests

Retrovirus and ATM-mediated neuroimmunodegeneration, oxidative stress, signal transduction, therapeutic intervention

Current Research

The focus of my research is on animal models for immunosuppression, neurodegeneration, and cancer. One uses a murine retrovirus called ts1, and the other uses mutant mice (Atm-/- mice) that do not produce the kinase ATM (ataxia telangiectasia mutated). The ts1 retrovirus is a mouse model for human HIV-AIDS and other neuroimmuno-degenerative syndromes. The Atm-/- mouse is a model for the human childhood genetic disorder ataxia-telangiectasia (A-T). These two models were specifically selected to complement each other.

Our goals are to understand the pathogenical mechanisms for both of these diseases, to test drugs to prevent T and neuronal cell loss in the ts1-infected mice, and to prevent lymphoma and neurodegeneration in Atm-/- mice. In both models, intracellular oxidative stress and oxidative stress-initiated pathways cause T cell dysfunction and neuronal death. The common involvement of oxidative stress in these two different diseases contributes to our understanding of shared mechanisms in human degenerative diseases and cancers. For example, we have recently found that ts1-mediated apoptosis is associated with p53 phosphorylation and mammalian target of rapamyacin (mTOR) activation as a result of oxidative stress. These findings suggest parallels in cell death mechanisms between ts1 and HIV-associated neurodegeneration and also in ts1 and ATM deficiency.

Over the past several years, we have published many papers reporting information about the mechanisms that cause cell damage in both diseases. We have also identified novel treatments for both syndromes that may be useful therapies in human cancer and neurodegenerative syndromes. Selected publications from the two areas of inquiry are described below.

Selected Publications

  1. Jiang Y, Scofield VL, Yan M, Qiang W, Liu N, Reid AJ, Lynn WS, Wong PK. Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by antioxidant treatment with a refined monosodium alpha-luminol (Galavit), J Virol, 80 (9), 4557-69, 2006
  2. Liu N, Scofield VL, Qiang W, Yan M, Kuang X, Wong PK. Interaction between endoplasmic reticulum stress and caspase 8 activation in retrovirus MoMuLV-ts1-infected astrocytes, Virology, 348 (2), 398-405, 2006
  3. Pusapati RV, Rounbehler RJ, Hong S, Powers JT, Yan M, Kiguchi K, McArthur MJ, Wong PK, Johnson DG. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc, Proc Natl Acad Sci U S A, 103 (5), 1446-51, 2006
  4. Qiang W, Kuang X, Liu J, Liu N, Scofield VL, Reid AJ, Jiang Y, Stoica G, Lynn WS, Wong PK. Astrocytes survive chronic infection and cytopathic effects of the ts1 mutant of the retrovirus Moloney murine leukemia virus by upregulation of antioxidant defenses, J Virol, 80 (7), 3273-84, 2006
  5. Yan M, Zhu C, Liu N, Jiang Y, Scofield VL, Riggs PK, Qiang W, Lynn WS, Wong PK. ATM controls c-Myc and DNA synthesis during postnatal thymocyte development through regulation of redox state, Free Radic Biol Med, 41 (4), 640-8, 2006
  6. Kim HT, Qiang W, Liu N, Scofield VL, Wong PK, Stoica G. Up-regulation of astrocyte cyclooxygenase-2, CCAAT/enhancer-binding protein-homology protein, glucose-related protein 78, eukaryotic initiation factor 2 alpha, and c-Jun N-terminal kinase by a neurovirulent murine retrovirus, J Neurovirol, 11 (2), 166-79, 2005
  7. Kuang X, Yan M, Liu N, Scofield VL, Qiang W, Cahill J, Lynn WS, Wong PK. Control of Atm-/- thymic lymphoma cell proliferation in vitro and in vivo by dexamethasone, Cancer Chemother Pharmacol, 55 (3), 203-12, 2005
  8. Liu N, Stoica G, Yan M, Scofield VL, Qiang W, Lynn WS, Wong PK. ATM deficiency induces oxidative stress and endoplasmic reticulum stress in astrocytes, Lab Invest, 85 (12), 1471-80, 2005
  9. Kim HT, Waters K, Stoica G, Qiang W, Liu N, Scofield VL, Wong PK. Activation of endoplasmic reticulum stress signaling pathway is associated with neuronal degeneration in MoMuLV-ts1-induced spongiform encephalomyelopathy, Lab Invest, 84 (7), 816-27, 2004
  10. Qiang W, Cahill JM, Liu J, Kuang X, Liu N, Scofield VL, Voorhees JR, Reid AJ, Yan M, Lynn WS, Wong PK. Activation of transcription factor Nrf-2 and its downstream targets in response to moloney murine leukemia virus ts1-induced thiol depletion and oxidative stress in astrocytes, J Virol, 78 (21), 11926-38, 2004

Contact Information


Mailing Address: P.O. Box 389, Smithville, Texas 78957
Physical Address: 1808 Park Road 1C, Smithville, Texas 78957
Phone: (512) 237-9425