Mary F. Kearney, Ph.D.
HIV DRP Host-Virus Interaction Branch
Building 535, Room 108D
Frederick, MD 21702-1201
Studies of Clinical Resistance
The Translational Research Section (TRS) is primarily responsible for advancing the clinical and translational research efforts of the Host-Virus Interaction Branch by developing and applying new technologies to characterize and identify the sources of persistent HIV-1 viremia despite antiretroviral therapy (ART) and to evaluate the effect of HIV-1 genetic diversity, expression, and low-frequency drug resistance mutations on the response to ART. Working closely with Dr. Frank Maldarelli in the Clinical Retrovirology Section, in consultation with Dr. John Coffin of Tufts University and Dr. John Mellors of the University of Pittsburgh, the TRS collaborates with research groups worldwide to perform studies of HIV-host interactions, viral persistence during therapy, sources of rebound viremia, and the evolution of resistance.
HIV-1 persists in patients on ART despite suppression to very low levels and usually rebounds to pretherapy levels if ART is stopped. The mechanisms that allow viremia to persist during therapy are not well understood. Their elucidation is imperative if HIV-1 infection is ever to be cured. Cellular reservoirs that harbor HIV-1 genomes and express viral RNA during ART are likely long-lived, proliferating cells that were infected prior to initiating therapy. By investigating the genetics of HIV-1 plasma RNA and cellular HIV-1 DNA and RNA, the TRS aims to reveal sources of persistent virus production on ART and the sources of rebound viremia after stopping ART. The TRS developed the gold-standard assays that allow for sequencing of HIV RNA and DNA in single virions and in single infected cells. These assays are applied to blood and tissues from HIV-1-infected donors to characterize the genetics of viremia in patients on and off ART.
Determining the frequency of rare, drug-resistant variants in untreated patients can provide important insights into the emergence of drug resistance and into the effective population size of HIV-1. The TRS previously developed an allele-specific PCR (ASP) assay capable of detecting specific drug resistance mutations present in 0.1-0.001% of the total virus population. More recently, the TRS developed an ultrasensitive single-genome sequencing (uSGS) assay that provides sequence information from thousands of HIV variants present in donors’ plasma, providing templates to investigate the linkage of drug resistance mutations and to perform studies on HIV-1 evolution. Ongoing studies include applying these and other ultrasensitive methods under development to samples collected from women before and after exposure to single-dose nevirapine (NVP) and in patients initiating standard-of-care ART to investigate the impacts of HIV-1 diversity, low-frequency drug-resistant variants, and effective population size on the response to ART.
Dr. Mary Kearney received her Ph.D. in Biology at Catholic University in 2007 under the direction of Drs. John Coffin, Sarah Palmer, and Venigalla Rao. She received The Benedict T. DeCicco Award for Excellence in Graduate Research in 2008. In 2001 she joined the HIV Drug Resistance Program (renamed the HIV Dynamics and Replication Program in 2015) as a Biologist in the Virology Core. In 2008 she was promoted to Head of the Translational Research Unit (renamed the Translational Research Section in 2020), where she oversees a team that investigates HIV genetics and expression in vivo, the sources of persistent viremia during antiretroviral therapy (ART), the sources of rebound viremia after stopping ART, the mechanisms for maintaining the HIV reservoir, and the mechanisms for the emergence of HIV drug resistance mutations. Dr. Kearney was awarded the NIH Director’s Award and NCI Group Award in 2012, the NCI Director's Award in 2015, the CCR Group Award in 2016, and the NIH Director’s Award in 2019. She was a consultant to the World Health Organization from 2010 to 2016, was the keynote speaker for the launch of the Bioinformatics Program at Hood College in 2015 and for the Center for AIDS Research Symposium at the University of Pennsylvania in 2019, and was appointed to the NIH Women Scientist Advisors (WSA) in 2018. She currently serves as Chair of the WSA Executive Committee and as an advisor to the Bioinformatics Program and Biology Department at Hood College. Dr. Kearney is the recipient of three Bench-to-Beside Awards, three NIH Intramural AIDS Targeted Antiviral Program Awards, and a U.S.–South Africa Initiative U01 Grant. In 2019 she was promoted to Senior Scientist.
Bale MJ, Kearney MF. Review: HIV-1 phylogeny during suppressive antiretroviral therapy. Curr Opin HIV AIDS. 2019;14(3):188-193.
Capoferri AA, Bale MJ, Simonetti FR, Kearney MF. Phylogenetic inference for the study of within-host HIV-1 dynamics and persistence on antiretroviral therapy. Lancet HIV. 2019;6(5):e325-e333.
McManus WR, Bale MJ, Spindler J, Wiegand A, Musick A, Patro SC, Sobolewski MD, Musick VK, Anderson EM, Cyktor JC, Halvas EK, Shao W, Wells D, Wu X, Keele BF, Milush JM, Hoh R, Mellors JW, Hughes SH, Deeks SG, Coffin JM, Kearney MF. HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy. J Clin Invest. 2019;130.
Van Zyl GU, Katusiime MG, Wiegand A, McManus WR, Bale MJ, Halvas EK, Luke B, Boltz VF, Spindler J, Laughton B, Engelbrecht S, Coffin JM, Cotton MF, Shao W, Mellors JW, Kearney MF. No evidence of HIV replication in children on antiretroviral therapy. J Clin Invest. 2017;127(10):3827-3834.
Wiegand A, Spindler J, Hong FF, Shao W, Cyktor JC, Cillo AR, Halvas EK, Coffin JM, Mellors JW, Kearney MF. Single-cell analysis of HIV-1 transcriptional activity reveals expression of proviruses in expanded clones during ART. Proc Natl Acad Sci U S A. 2017;114(18):E3659-E3668.
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Microbiology and Infectious Diseases
This page was last updated on September 1st, 2020