We plan to establish a Pilot Proteomics Center that will apply powerful new proteomics technologies to broadly investigate changes in protein abundances resulting from the pathologic events associated with concomitant lentiviral infection and substance abuse as well as from pharmacologic interventions designed to treat these pathologies. These complex interactions will be studied in human immunodeficiency virus, type 1 (HlV)-infected and -uninfected subjects, treated or not with exogenous opioids as well as in well-defined nonhuman primate models of lentiviral pathogenesis induced by the simian immunodeficiency virus (SIV). In so doing, we aim to identify the quantitative proteomic biosignatures and profiles that define and predict the impact of opioids on lentiviral disease progression, with particular emphasis on the neurological sequelae that accompany the acquired immune deficiency syndrome (AIDS). These efforts will benefit from execution in a manner that benefits from the extensive experience of the investigators, existing sample sets, comparison of human and non-human primate responses, and the extensive use of complementary data and techniques (e.g. immunologic and microarray assays). Through utilizing PNNI's experience and expertise in mass spectrometry for proteomic applications, the Proteomics Core will use high-resolution separations and mass spectrometry to support the following three projects. Project 1: To use high-throughput proteomics to define changes in the cerebrospinal fluid (CSF) proteome in HIV infection related to brain injury, intrathecal immune activation, CNS infection, and opioid use. Project 2: To explore the effect of opioids on the proteomic, immunologic, and genetic, signatures of nonhuman primates (NHP) that are uninfected or that have pathogenic or non-pathogenic SIV infection. Project 3: To evaluate the immunomodulatory effects of heroin, buprenorphine, and protease inhibitors in opioid-dependent individuals, infected or not with HIV.

Public Health Relevance

The application of proteomics to study the relationship between inflammation and lentiviral disease progression in the context of opioid use and treatment has direct relevance in improving the health and potential clinical treatments for these individuals. Such studies will allow a better understanding of both the natural course of lentiviral disease and the impact of opioid use and treatment on such disease progression.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1-MXS-M (18))
Program Officer
Lin, Yu
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Battelle Pacific Northwest Laboratories
United States
Zip Code
Price, Richard W; Spudich, Serena S; Peterson, Julia et al. (2014) Evolving character of chronic central nervous system HIV infection. Semin Neurol 34:7-13
Peterson, Julia; Gisslen, Magnus; Zetterberg, Henrik et al. (2014) Cerebrospinal fluid (CSF) neuronal biomarkers across the spectrum of HIV infection: hierarchy of injury and detection. PLoS One 9:e116081
Dominy, Stephen S; Brown, Joseph N; Ryder, Mark I et al. (2014) Proteomic analysis of saliva in HIV-positive heroin addicts reveals proteins correlated with cognition. PLoS One 9:e89366
Piehowski, Paul D; Petyuk, Vladislav A; Sandoval, John D et al. (2013) STEPS: a grid search methodology for optimized peptide identification filtering of MS/MS database search results. Proteomics 13:766-70
Price, Richard W; Peterson, Julia; Fuchs, Dietmar et al. (2013) Approach to cerebrospinal fluid (CSF) biomarker discovery and evaluation in HIV infection. J Neuroimmune Pharmacol 8:1147-58
Grund, Birgit; Wright, Edwina J; Brew, Bruce J et al. (2013) Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect. J Neurovirol 19:383-92
Brown, Joseph N; Ortiz, Gabriel M; Angel, Thomas E et al. (2012) Morphine produces immunosuppressive effects in nonhuman primates at the proteomic and cellular levels. Mol Cell Proteomics 11:605-18