Center for Comparative Medicine
SOM: Pathology and Laboratory Medicine
University of California, Davis
Molecular mechanisms of viral pathogenesis in animal models (non-human primates), Human immunodeficiency virus (HIV) and AIDS (pathogenesis, vaccines, drug therapy), Multiplex diagnostics and biomarkers for infectious diseases and cancer.
Dr. Paul Luciw is a virologist with extensive expertise in many aspects of virology, with additional experience in microbiology, immunology, 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 and other diseases. His recent translational research has focused on the development of novel technologies for diagnosis of infectious diseases (emphasis on tuberculosis) and cancer. Much of Dr. Luciw’s research involves close interactions with veterinarians, staff research specialists, and animal health technicians at the California National Primate Research Center (CNPRC) (California National Primate Research Center), which is located in close proximity to CCM. He served as Leader of the Infectious Disease Research Unit at the CNPRC which consists of 8 principal investigators and several key affiliate investigators, all of whom develop and use nonhuman primate models for basic and translational research on a broad range of infectious pathogens. Currently, he is Professor Emeritus on formal recall and remains active in research, teaching, and service activities at UC Davis.
Mechanisms of Viral Pathogenesis and Latency
The major part of Dr. Luciw’s research focused on using the non-human primate model to study mechanisms of pathogenesis of simian immunodeficiency virus (SIV) and chimeric simian-human immunodeficiency virus (SHIV). These simian AIDS studies were based primarily on molecular virology analysis of viral clones in rhesus monkeys. Through collaborative interactions, he has been involved in evaluating vaccines for HIV/AIDS in the simian AIDS model. This model enables challenge of immunized animals with pathogenic virus and informs attempts to define correlates of protective immunity. Dr. Luciw has also participated in projects that used this preclinical model to analyze the sub-anatomic distribution of anti-retroviral drugs in vivo in both lymphoid and non-lymphoid targets of virus. This involved the development and application of novel mass spectrometry imaging of tissue samples collected from multiple organs of rhesus monkeys treated with several anti-retroviral drugs. The findings indicate the need to improve penetration of anti-retroviral drugs into tissue/organ targets of virus. His laboratory has tested novel pharmacologic approaches targeted at inducing virus (SIV or HIV) from latent cell reservoirs with the goal of eliminating virus.
An ongoing collaborative study on neurological disease associated with HIV/AIDS, involving Dr. Luciw, uses the non-human primate model of chronic SIV infection to determine the immunological, inflammatory, and neurobiological basis of age-related cognitive decline in HIV infected individuals receiving anti-retroviral therapy. This project analyzes the role of monocytes as well as CD4+ T-cells in the central nervous system to determine contributions of these immune cells to neuroinflammation. The findings may enable rational selection of adjunctive therapies and help to define timing for maximal therapeutic impact, particularly for HIV-associated neurological disorder (HAND).
A highly innovative imaging capability using the PET-Explorer (PET-EX) scanner developed at UC Davis, provides a robust method for live-phase, minimally invasive and quantitative 3D visualization of virus in multiple target tissue/organ sites. Dr. Luciw has been involved in pilot studies aimed at using the preclinical model of simian AIDS to optimize the whole body PET-EX imaging technology for detection of viral targets and eventually for monitoring efficacy of anti-latency therapies in essentially all tissue/organ reservoirs of virus.
Translational Research for Infectious Diseases and Cancer
For translational research, Dr. Luciw and his colleagues have developed multiplex microbead immunoassay technology (Luminex) for detection of antibodies to multiple infectious agents and host response immunomodulatory proteins. With a focus on tuberculosis, his laboratory has used multiplex immunoassays for analysis of cytokines, chemokines, and inflammatory mediators as well as antibodies to multiple antigens in clinical trials of patients infected with Mycobacterium tuberculosis. Importantly, these robust multiplex assays aim to significantly improve diagnosis and prognosis of tuberculosis in endemic countries.
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 (i.e., growth factors, proteinases, oncogenes, angiogenesis factors, as well as a broad range of immunomodulators).