Overview: Dr. Paul Luciw is a virologist with extensive experience in many aspects of virology, cell biology, and molecular biology. The main emphasis of his research is on viruses that establish persistent infection; these include retroviruses that cause immunodeficiency and herpesviruses associated with cancer. His recent translational research has focused on the development of novel multiplex detection technologies for studies of infectious diseases and cancer.
Mechanisms of viral pathogenesis and latency: For studies on simian immunodeficiency virus (SIV), a major aim of Dr. Luciw’s research is to identify viral determinants of pathogenesis in the non-human primate model (i.e., rhesus monkeys) for AIDS. This research aims to define functional domains on viral proteins and to analyze molecular mechanisms regulating viral transcription in latency and reactivation. He is testing novel pharmacologic approaches targeted at inducing virus (SIV, HIV, recombinant SHIV strains) from latent cell reservoirs in nonhuman primates. Coupled with highly active antiretroviral therapy, induction of latent virus by compounds that activate specific transcription factors and remodel chromatin, could lead to elimination of virus from an infected individual. He is also studying molecular mechanisms regulating chronic infection of cats with feline immunodeficiency virus (FIV); this includes analysis of viral reservoirs and reactivation of latent virus. With collaborators, Dr. Luciw investigates the oncogenic herpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV), with a focus on viral genes regulating signal transduction and transcription and on post-translational modifications of chromatin proteins during viral infection. The goal is to understand the molecular mechanisms by which this oncogenic herpesvirus alters cell functions to favor viral replication and mediate tumorigenesis.
Vaccination against infectious agents: A component of Dr. Luciw's research has involved the testing and development of recombinant anti-viral vaccines in the SIV/monkey and feline immunodeficiency virus (FIV)/cat model systems; these studies are directly relevant for the development of vaccines against the human immunodeficiency virus (HIV) and AIDS. A goal of this vaccine research is to elucidate molecular and cellular mechanisms that account for induction of anti-viral immune responses after DNA immunization. In addition, his research has extended to collaborations that use non-human primates to evaluate novel vaccines against Mycobacterium tuberculosis.
Clinical/translational research and multiplex biomarker detection technology: For translational research of infectious diseases, Dr. Luciw has developed multiplex immunoassay technology for detection of antibodies to multiple infectious agents and analysis of host response immunomodulatory proteins to infection. To study host responses to Mycobacterium tuberculosis, his laboratory has developed and applied multiplex immunoassays for studies of cytokines, chemokines, and inflammatory mediators as well as antibodies to multiple antigens of this pathogen in infected nonhuman primates and humans. Importantly, these robust multiplex assays have strong potential for significantly improving diagnosis and prognosis of tuberculosis. He has also applied this novel immunoassay for detection of antibodies to multiple infectious agents of mouse (UC Davis Mouse Biology Program) and rhesus monkey (California Primate Center). For application to studies on mechanisms of tumorigenesis, Dr. Luciw has been developing multiplex immunoassay systems that simultaneously detect multiple cell signaling molecules (phosphotyrosine kinsease and substrates, phosphoserine/threonine kinsese and substrates, transcription factors). This system enables simultaneous analysis of multiple signal transduction pathways and multiple components of these pathways in cancer cell line models and tumors. His laboratory also performs multiplex analysis of protein targets in plasma of cancer patients, with the goal of defining rapid and effective methods for diagnosis and prognosis. These plasma targets include biomarkers associated with various stages of tumorigenesis (growth factors, proteinases, oncogenes, angiogenesis factors, etc.).
Biodefense and emerging infectious diseases: Dr. Luciw is the Director of the “Animal Resources and Laboratory Services Core” of the Pacific Southwest Regional Center for Excellence in Biodefense and Emerging Infectious Diseases. The mission of this Core is to coordinate access of investigators to the professional expertise, technical support, instrumentation, and infrastructure for animal modeling that are located at UC Davis. Core activities foster collaborative interactions among scientists throughout the Center network, resulting in expanded research that addresses the biodefense mission of NIH.
Venue: In the Center for Comparative Medicine building on the UCD campus, which is adjacent to the California Primate Center, Dr. Luciw has been assigned 1200 sq. ft. of lab space for molecular virology. At both Centers, he has access to shared space and equipment for growth and analysis of infectious viral and bacterial pathogens in biosafety containment level 2 and level 3 labs. In addition, to support translational research, Dr. Luciw has been assigned lab space for the Clinical Proteomics Core that he directs at the Research 3 Building at the UCD Medical Center in Sacramento.
Gardner, M.B. and P.A. Luciw (2008) Macaque Models for Human Infectious Diseases. Institute for Laboratory Animal Research. 49:220-255.
Khan, I.H., V.V. Krishnan, M. Ziman, K. Janatpour, T. Wun, P.A. Luciw, and J. Tuscano (2008) Comparison of Multiplex Suspension Array Large-Panel Kits for Profiling Cytokines and Chemokines in Rheumatoid Arthritis Patients. Cytometry: Part B - Clinical Cytometry 76:159-68.
Dubie R.A., S. Maksaereekul, B.L. Shacklett, D. Lemongello, K.S. Cole, F. Villinger, S. Blozis, P.A. Luciw, and E.E. Sparger. (2008) An IL-15 expression plasmid enhances vaccine immunogenicity and efficacy of a vif-deleted simian immunodeficiency virus proviral DNA vaccine. Virology 386:109-21.
Izumiya Y., C. Izumiya, D. Hsia, T.J. Ellison, P.A. Luciw, and H-J. Kung. (2009) NF-kappaB serves as a cellular sensor of KSHV latency and negatively regulates the viral transactivator K-Rta. J. Virol. 83:4435-46.
Khan I., J. Zhao, P. Ghosh. M. Ziman, C. Sweeney, H-J. Kung, and P. Luciw (2009) Multiplex microbead auspension arrays for simultaneous analysis of ErbB family of receptor tyrosine kinases: activation and dimerization studies in breast cancer cells. ASSAY and Drug Devel. Technologies 8: 27-36.
Krishnan, V.V., I.H. Khan, and P.A. Luciw (2009) Multiplexed microbead immunoassays by flow cytometry for molecular profiling: Basic concepts and proteomics applications. Current Reviews in Biotechnology. 29:29-43.
North, T.W., J. Higgens, J.D. Deere, T.L. Hayes, A. Villalabos, L. Adamson, B.L. Shacklett, R.F. Schinazi, and P.A. Luciw. (2010) Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS. J. Virol. 84: 2913-2922.
Chang P-C.,Y. Izumiya,C-Y. Wu, L.D. Fitzgerald, M. Campbell, T.J. Ellison, K.S. Lam, P.A. Luciw, and H-J. Kung. (2010) Kaposiâ€™s sarcoma associated herpesvirus (KSHV) encodes a SUMO E3 ligase which is SIM-dependent and SUMO2/3-specific. J. Biol. Chem. 285: 5266-5273.
Ho C, R. Sangha, L. Beckett L, M. Tanaka, D.H. Lau, D.B. Eisen, R.A. Burich, P. Luciw, I. Khan, P.C. Mack, D.R. Gandara, A.M. Davie. Escalating weekly doses of cetuximab and correlation with skin toxicity: A phase I study. Invest. New. Drugs. 2010 Feb 12. [Epub ahead of print].
Campbell, M., W-R. Lie, J. Zhao, D. Hayes, J. Mistry, H-J. Kung, P.A. Luciw, and I.H. Khan. (2010) Multiplex analysis of Src family kinase signaling by microbead suspension arrays. ASSAY and Drug Devel. Technologies. 8:488-96.
Chen C-I, D.C. Clark, P. Pesavento, N.W. Lerche, P.A. Luciw, W.K. Reisen, and A. C. Brault (2010) Comparative Pathogenesis of Epidemic and Enzootic Chikungunya Viruses in a Pregnant Rhesus Macaque Model. Am. J. Trop. Med.
Deere, J.D., J. Higgins, E. Cannavo, A. Villalobos, L. Adamson, R.F. Schinazi, P.A. Luciw, and T.W. North. (2010) Low-level viremia persists despite suppressive highly active antiretroviral therapy in rhesus macaques infected with RT-SHIV. PLoS One. 5(7):e11640.
Ravindran, R., I.H. Khan, V.V. Krishnan, M. Ziman, J.K. Frasier, R. Bates, S.M. Griffey, J.R. Fahey, L.V. Kendall, P.A. Luciw. (2010) Validation of multiplex microbead immunoassay for simultaneous serodiagnosis of multiple infectious agents in laboratory mice. J. Immunol. Methods. 363:51-59.
Chang P.C., L.D. Fitzgerald, D.A. Hsia, Y. Izumiya, C.Y. Wu, W.P. Hsieh, S.F. Lin, M. Campbell, K.S. Lam, P.A. Luciw, C.G. Tepper, H.J. Kung. (2011) Histone demethylase JMJD2A regulates KSHV replication and is targeted by a viral transcriptional factor. J. Virol. 85:3283-93.
Luciw, P.A., K.L. Oslund, X-W. Yang, L. Adamson, R. Ravindran, D. Canfield, R. Tarara, L. Hirst, M. Christensen, N. W. Lerche, H. Offenstein, D. Lewinsohn, F. Ventimiglia, L. Brignolo, E.R. Wisner, and D.M. Hyde (2011) Stereologic Analysis of Bacterial Load and Lung Lesions in Nonhuman Primates (Rhesus Macaques) Experimentally Infected with Mycobacterium tuberculosis. Am J Physiol - Lung Cell Mol Physiol. 301:L731-8.
Khan I.H., R. Ravindran, V.V. Krishnan, I. Nawaz Awan, S.K.A. Rizvi, M.A.N. Saqib, M.I. Shahzad, S. Tahseen, G. Ireton, C. Goulding, P. Felgner, K. DeRiemer, A. Khanum, and P.A. Luciw. (2011) Plasma antibody profiles as diagnostic biomarkers for tuberculosis. Clin Vaccine Immunol. 18:2148-53.
Campbell M, Chang PC, Huerta S, Izumiya C, Davis R, Tepper CG, Kim KY, Shevchenko B, Jung JU, Luciw PA, Kung HJ, Izumiya Y. (2012) Protein arginine methyltransferase 1-directed methylation of Kaposi's sarcoma-associated herpesvirus LANA. J Biol Chem. 287:5806-18.
Murphy B., N. Vapniarsk., C. Hillman, D. Castillo, S. McDonnel, Moore P., P.A. Luciw and E.E. Sparger. (2012) FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection. Retrovirology 7:9:12.