Methamphetamine and HIV-1 Infection: Targeted Nanoparticles for Gene Silencing

DESCRIPTION (provided by applicant): Receipt of a K01 award will allow the applicant to successfully transition into an independent investigator by providing protected time for the acquistion of new knowledge and technical skills by undertaking further research in the rapidly advancing field of nanotechnology. The objective of this application is to bridge 2 scientific disciplines by integrating nanotechnology with research on the role of drug abuse in HIV-1 infections. The latter was the basis for the applicant's post-doctoral fellowship funded by a National Research Service Award. Additional training in nanotechnology will significantly assist the applicant to expand her research direction by applying this new expertise to the development of innovative methods to control HIV-1 infections associated with drug abuse. Under the sponsorship of Dr. Paras Prasad, an internationally known expert in nanomaterials, and with guidance from her co-sponsor Dr. Stanley Schwartz, known for his research in drugs of abuse and HIV-1 infections, the applicant will receive didactic and laboratory training in applying nanotechnology to biomedical applications. Bioconjugated nanoparticles have great potential for studying intracellular processes at the single-cell level using high-resolution imaging. This proposal will investigate the effectiveness of organically modified silica (ORMOSIL) nanoparticles as a platform to deliver small interfering (siRNA) targeted to specific genes (galectin-1, protein disulfide isomerase, thioredoxin and peroxiredoxin) relevant to HIV-1 infections whose expression has been shown by the applicant to be modulated by methamphetamine. The inertness and non-toxicity of ORMOSIL nanoparticles render them promising materials for biomedical and clinical applications. The interdisciplinary environment, involving both basic science (Chemistry) and clinical (Medicine) departments, supporting this project is unique with state of the art facilities. The research laboratories of the Department of Medicine in the Buffalo General Hospital are on the Buffalo-Niagara Medical Campus including the Center of Excellence in Bioinformatics and Life Sciences and the Roswell Park Cancer Institute. She also will utilize the facilities of the Institute for Lasers, Photonics and Biophotonics on the main campus of the University at Buffalo. The applicant's career goals are to become an independently funded, academic scientist, directing her own research laboratory. By bridging the fields of nanotechnology, addiction research, and retrovirology, these studies may yield an innovative and powerful, new methodology providing further insight into and new interventions for the serious public health issues of drug abuse and HIV-1 infections.