Leidos Biomedical Research, Inc.
Frederick National Laboratory for Cancer Research
Frederick, MD 21702-1201
Brandon F. Keele, Ph.D., is a Principal Investigator/Principal Scientist in the AIDS and Cancer Virus Program (ACVP) at the Frederick National Laboratory for Cancer Research and currently heads both the Retroviral Evolution Section and the Viral Evolution Core. Dr. Keele obtained his Ph.D. at Brigham Young University while studying the mechanism and diversity of virus trapped by follicular dendritic cells during HIV-1 infection. Dr. Keele then worked at the University of Alabama at Birmingham first as a post-doctoral fellow and then as an Assistant Professor in the Department of Medicine. While as a post-doctoral fellow with Dr. Beatrice Hahn, Dr. Keele was the lead author describing the geographic origins of pandemic HIV-1. Dr. Keele and colleagues then discovered that SIVcpz is pathogenic to chimpanzees and can lead to significant population decline. In collaboration with Dr. George Shaw and the Center for HIV/AIDS Vaccine Immunology (CHAVI), Dr. Keele utilized a novel limiting dilution PCR to elucidate the viral dynamics of transmission and early diversification in HIV-1 infected humans. Early sampling and these techniques allowed for the discovery that the vast majority of HIV-1 infections occur due to a single transmitted founder virus that can be unambiguously identified and studied. Dr. Keele established the Retroviral Evolution Section and the Viral Evolution Core within the ACVP to expand our understanding of transmission, viral evolution, eradication and vaccine-elicited prevention using nonhuman primate models.
The Retroviral Evolution Section (RES) utilizes cutting edge technology to solve challenging and complex research questions in HIV/AIDS research with an emphasis in nonhuman primate models and SIV. The Retroviral Evolution Section studies viral transmission and subsequent evolution, as well as viral reservoir establishment/maintenance as a basis for HIV Cure research. We utilize sequencing, genetic analyses, and molecular biology to better understand both the natural course of infection and potential sites and mechanisms of intervention. Recently, using MRI and visual dyes, Dr. Keele has defined the likely routes of virus spread from sites of mucosal challenge through local draining lymphatics. Further, Dr. Keele has focused on characterizing viral stocks for use in NHP models. Specifically Dr. Keele has recently demonstrated that transfection-produced virus has fewer cytokines but also less Env compared to infection-produced stocks, which may explain the in vivo infectivity differences between the two methods of virus production. Dr. Keele has since expanded the characterization of infectious stocks to generating synthetic swarms using both a molecularly tag approach as well as novel approach which inserts a genetic barcode within the actual viral genome. These SIV stocks are being used to track individual viral variants during acute infection and to determine the timing and persistence of long-lived viral reservoirs.
The Viral Evolution Core (VEC) provides expertise and innovative sequencing techniques, molecular cloning, as well as viral evolution analyses to support extramural and intramural investigators in order to increase the overall understanding of viral transmission, early viral diversification, immune selection, genetic adaptation to new hosts, preclinical vaccine efficacy, and viral eradication with a major focus on exploiting the unique advantages afforded by utilizing non-human primates and SIV infection. Currently the VEC utilizes single genome amplification (SGA) and deep sequencing approaches (including Illumina, 454,and SMRT sequencing technologies) to identify genetic changes in viral populations. These approaches have helped develop mucosal transmission models where most animals are infected with one or a few variants thereby recapitulating HIV-1 infection in humans. These include rectal, vaginal and penile models of transmission. Furthermore, the VEC is utilizing these same approaches to help establish the efficacy of preventative measures including vaccines, microbicides, and passive administered neutralizing antibodies. Further, we have helped develop and characterize several divergent SIV, SHIV, and stHIV viruses for NHP research. Dr. Keele has also pioneered an innovative approach to isolate and sequence viral RNA and DNA directly from HIV/SIV infected tissue as well as from individual cells/sections that are isolated by laser-capture microdissection. These assays are currently being utilized to pinpoint the exact conditions and events surrounding viral transmission in nonhuman primates.