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 or HIV) from latent cell reservoirs. 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. Dr. Luciw’s collaborative studies on the oncogenic herpesvirus, Kaposi’s sarcoma-associated herpesvirus (KSHV), have focused 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.
Translational Research for Infectious Diseases and Cancer
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 these responses to Mycobacterium tuberculosis, his laboratory has used multiplex immunoassays for studies of cytokines, chemokines, and inflammatory mediators as well as antibodies to multiple antigens of this pathogen in 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 National Primate Research 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 kinase 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 has also performed 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.).
Ravindran R, Krishnan VV, Khanum A, Luciw PA, Khan IH. (2013) Exploratory study on plasma immunomodulator and antibody profiles in tuberculosis patients. Clin Vaccine Immunol. 20:1283-90.
Krishnan VV, Ravindran R, Wun T, Luciw PA, Khan IH, Janatpour K. (2014) Multiplexed measurements of immunomodulator levels in peripheral blood of healthy subjects: Effects of analytical variables based on anticoagulants, age, and gender. Cytometry B Clin Cytom. doi: 10.1002/cyto.b.21147. [Epub ahead of print]
Chromy BA, Eldridge A, Forsberg JA, Brown TS, Kirkup BC, Jaing C, Be NA, Elster E, Luciw PA. (2013) Wound outcome in combat injuries is associated with a unique set of protein biomarkers. J Transl Med. 11:281. doi: 10.1186/1479-5876-11-281.
Be NA, Allen JE, Brown TS, Gardner SN, McLoughlin KS, Forsberg JA, Kirkup BC, Chromy BA, Luciw PA, Elster EA, Jaing CJ. (2014) Microbial profiling of combat wound infection through detection microarray and next-generation sequencing. J Clin Microbiol. pii: JCM.00556-14.
Deere JD, Kauffman RC, Cannavo E, Higgins J, Villalobos A, Adamson L, Schinazi RF, Luciw PA, North TW. (2014) Analysis of multiply spliced transcripts in lymphoid tissue reservoirs of rhesus macaques infected with RT-SHIV during HAART. PLoS One. 9(2):e87914.
North TW, Villalobos A, Hurwitz SJ, Deere JD, Higgins J, Chatterjee P, Tao S, Kauffman RC, Luciw PA, Kohler JJ, Schinazi RF. (2014) Enhanced Antiretroviral Therapy in Rhesus Macaques Improves RT-SHIV Viral Decay Kinetics. Antimicrob Agents Chemother. 2014 Jul;58(7):3927-3933.
Krishnan, Krish (Viswanathan)
Adjunct Associate Professor
Biostatistics and Computational Modeling
Associate Project Scientist