Mary F. Kearney, Ph.D.
Mary F. Kearney, Ph.D.
Dr. Kearney conducts research on the emergence of HIV drug resistance, the persistence of HIV during antiretroviral treatment (ART), and the sources of rebound viremia after stopping ART.¬† Her studies, in collaboration with the Clinical Retrovirology Section led by Frank Maldarelli, have demonstrated that a diverse population of HIV-infected cells persist during ART, that some infected cells proliferate despite ART, and that residual viremia during ART can result from viral expression from these cells. ¬†Dr. Kearney heads the Translational Research Section, which aims to understand the genetics, evolution, and persistence of HIV and other RNA viruses and to design new approaches toward targeting and killing infected cells.¬†Currently, she also serves as a member of the NIH Women Scientists Advisors (WSA) Executive Committee and as Chair of the CCR WSA Committee; these groups promote career development and address issues affecting women scientists.
1) drug resistance, 2) viral persistence, 3) HIV residual viremia, 4) HIV cure,¬†5) viral evolution, 6) viral genetics
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 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 Frank Maldarelli in the Clinical Retrovirology Section, in consultation with John Coffin of Tufts University and 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 individuals 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 donors to characterize the genetics of viremia in individuals on and off ART.
Determining the frequency of rare, drug-resistant variants in untreated individuals 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‚Äô 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 before and after exposure to ART to investigate the impacts of HIV-1 diversity, low-frequency drug-resistant variants, and effective population size on the response to treatment.
Selected Key Publications
Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors.Proc. Natl. Acad. Sci. USA. 116: 25891-25899, 2019. [ Journal Article ]
HIV infected T cells can proliferate in vivo without inducing expression of the integrated provirus.Front Microbiol. 10: 2204, 2019. [ Journal Article ]
- J. Clin. Invest. 130: 126714, 2019. [ Journal Article ]
- J. Clin. Invest. 127: 3827-3834, 2017. [ Journal Article ]
Single-cell analysis of HIV-1 transcriptional activity reveals expression of proviruses in expanded clones during ART.Proc. Natl. Acad. Sci. USA. 114: E3659-E3668, 2017. [ Journal Article ]
Dr. Kearney received her Ph.D. in Biology at Catholic University in 2007 under the direction of 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 viral genetics and expression in vivo, the sources of persistent HIV 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 drug-resistance mutations in HIV and other RNA viruses.¬† Dr. Kearney was awarded the NIH Director‚Äôs Award and NCI Group Award in 2012, the NCI Director's Award in 2015, the CCR Group Award in 2016, and the NIH Director‚Äôs 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 elected to the NIH Women Scientist Advisors (WSA) in 2018.¬† She currently serves as Chair of the CCR WSA Committee, a member of the NIH WSA Executive Committee, and an advisor to the Biomedical Science and Bioinformatics Program at Hood College.¬† Dr. Kearney is the recipient of three Bench-to-Beside Awards, three NIH Intramural AIDS Targeted Antiviral Program Awards, a U.S.‚ÄďSouth Africa Initiative U01 Grant, and an Office of AIDS Research Congressional Award. ¬†In 2019 she was promoted to Senior Scientist.
|Valerie Boltz M.S.||Research Biologist|
|Adam Capoferri||Predoctoral Fellow (Graduate Student)|
|Jennifer Groebner Ph.D.||Postdoctoral Fellow (CRTA)|
|Jenna Hasson||Postbaccalaureate Fellow (CRTA)|
|Mary Grace Katusiime Ph.D.||Postdoctoral Fellow (Visiting)|
|Andrew Musick M.S.||Research Associate II (Contr.)|
|Sean Patro Ph.D.||Postdoctoral Fellow (CRTA)|
|Jason W. Rausch, Ph.D.||Staff Scientist|
|Wei Shao Ph.D.||Programmer / Analyst (Contr)|
|Rachel Sklutuis||Postbaccalaureate Fellow (CRTA)|
|Jonathan Spindler||Research Biologist|
|Ann Wiegand M.S.||Research Biologist|
Postdoctoral Fellow, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
Ph.D. Student, Cornell University, New York, NY
Senior Manager, Alliance Management at Foundation Medicine, Cambridge, MA
Undergraduate Student, Hood College, Frederick, MD
Postdoctoral Research Associate, University of North Carolina HIV Cure Center, Chapel Hill, NC
Predoctoral Fellow, NIH-Oxford-Cambridge Scholars Program, Oxford, UK (Alex Compton's staff, HIV Dynamics and Replication Program)
Molecular Biology Technician, National Institute of Allergy and Infectious Diseases, Bethesda, MD
Undergraduate Student, Bates College, Lewiston, ME
Investigator, Swedish Institute for Infectious Disease Control, Solna, Sweden
Ph.D. Student, University of Notre Dame, Notre Dame, IN
Physician, Copenhagen University, Copenhagen, Denmark
Undergraduate Student, Hood College, Frederick, MD
Ph.D. Student, University of Maryland, College Park, MD
Production Planner, Northrop Grumman, Herndon, VA
Cofounder and Chief Executive Officer, HubHaus LLC, San Francisco, CA; Physician, Allied Pain and Spine Institute, San Jose, CA
New Investigator Scholarships, Conference on Retroviruses and Opportunistic Infections
Sean Patro and Jenna Hasson were awarded New Investigator Scholarships to present their research findings at the 2020 Conference on Retroviruses and Opportunistic Infections (CROI). Previous CROI scholarship awardees include Andrew Musick in 2017 and 2018 and Chad Coomer in 2014.
2019 NIH Director's Award
Mary Kearney received a 2019 NIH Director's Award as a member of the NIH Women Scientists Advisors (WSA) Executive Committee. Nominated by the NIH Office of the Director, the Executive Committee members received this team award for leadership of the WSA in promoting recruitment, retention, and recognition of women scientists and fair treatment with respect to salary and work environment.
2018 Leidos Outstanding Achievement Award
Wei Shao received a Leidos Outstanding Achievement Award in 2018 for developing the Retroviral Integration Site Database (https://rid.ncifcrf.gov) and the Proviral Sequence Database (https://pvsdb.cancer.gov).
2015 NCI Director's Award
Members of the NCI HIV Integration Sites Analysis (ISA) team received a group award at the NCI Director's Award ceremony in November 2015 "for discoveries on HIV survival during antiretroviral therapy, revealing the importance of integration site and clonal expansion." The ISA group award recipients included Stephen Hughes, Andrea Ferris, Shawn Hill, Mary Kearney, Frank Maldarelli, Wei Shao, and Jonathan Spindler (HIV DRP); Francesco Simonetti (University of Milan); John Coffin (Tufts University); John Mellors (University of Pittsburgh); and David Wells, Ling Su, and Xiaolin Wu (Leidos Biomedical Research, Inc.).
XMRV Working Group Received NIH Director's Award
Presentations at the 2009 Cold Spring Harbor Retroviruses Meeting in May 2009 suggested that xenotropic murine leukemia virus-related virus (XMRV), a novel gammaretrovirus with a potential link to prostate cancer and chronic fatigue syndrome, might be present in ~3% of the U.S. population, raising both public health issues and concern for contamination of the nation's blood supply. In response, the Intramural Research Program (IRP) of the National Cancer Institute immediately formed a multidisciplinary XMRV Working Group and charged the group with developing, implementing, and making available diagnostic reagents for rapid, accurate, and reliable detection of XMRV nucleic acids, antigens, and infectious virus. The group developed an action plan, and within three months, the SAIC Protein Expression Laboratory reported construction of 40 recombinant clones expressing all XMRV antigens and their subsequent purification for use as immunological reagents in December 2009. Importantly, these reagents were also made available (through the NIH AIDS Reagent Program) to the extramural community to accelerate XMRV research and allow sharing of a common set of reagents. A parallel effort in the HIV Dynamics and Replication Program resulted in establishing an assay to quantify XMRV DNA (from tissue) and RNA (from plasma) in November and December 2009, respectively. Since ultrasensitive XMRV nucleic acid detection methods were not available, this required in-house development and standardization, using the existing manpower and financial resources of the HIV DRP. In response to the need for "authentic" viral antigens for the development and standardization of immunological reagents by the Viral Technology Laboratory, the large-scale virus culture facilities of the SAIC AIDS and Cancer Virus Program were recruited for XMRV production. Finally, researchers of the HIV DRP developed the DERSE indicator cell line for detection of infectious XMRV. In contrast to traditional virological methods, this novel assay reduced the time needed to detect low levels of replicating XMRV in cell culture from months to a matter of weeks.
Subsequent studies have demonstrated that XMRV does not pose a threat to public health. Despite this, events between October 2009 and October 2010 highlighted the ability of dedicated scientists of the IRP to respond very quickly to a potential public health crisis by assembling a multidisciplinary team with a single goal of rapidly preparing, standardizing, and making available reagents for diagnostic virology. In every instance, reagents were prepared with existing manpower and resources, and without a serious interruption in the normal work flow or productivity of each group involved. Their non-XMRV work continued unimpeded. The success of this effort relied on close cooperation between all groups to establish and meet important deadlines. In addition to their individual contributions, the XMRV Working Group made reagents and technologies available to the general scientific community, and performed additional diagnostic analysis of samples supplied by federal, intramural, and extramural laboratories. In February 2012, the external XMRV Working Group (the Blood XMRV Scientific Research Working Group) received a Special Recognition Award from the Department of Health and Human Services, recognizing their exemplary team performance for "evaluating XMRV, a potential threat to the blood supply." In July 2012, members of the IRP XMRV Working Group were similarly recognized for their outstanding work by receiving the NIH Director's Award.
The IRP XMRV Working Group included:
Stuart Le Grice, HIV DRP
Alan Rein, HIV DRP
Vineet KewalRamani, HIV DRP
Mary Kearney, HIV DRP
James Hartley, Protein Expression Laboratory, SAIC-Frederick
Rachel Bagni, Viral Technology Laboratory, SAIC-Frederick
Jeffrey Lifson, AIDS and Cancer Virus Program, SAIC-Frederick
The NIH Director's Award to the IRP XMRV Working Group was highlighted in an issue of The Poster newsletter (link to NIH Director's Award feature).
Award for Excellence in Graduate Research, Catholic University of America
Mary Kearney was awarded The Benedict T. DeCicco Award for Excellence in Graduate Research in 2008 by the Biology Faculty of the Catholic University of America.
The Kearney Lab
Front row (left to right): Sean Patro, Mary Kearney, Valerie Boltz, Ann Wiegand, Jennifer Groebner
Back row (left to right): Andrew Musick, Aurelie Niyongabo, Jenna Hasson, Michael Bale, John Coffin, Jonathan Spindler, Wei Shao
Not shown: Rachel Sklutuis, Mary Grace Katusiime, Adam Capoferri, Jason Rausch
Current Lab Members
Valerie Boltz, M.S., Research Biologist
Valerie earned her M.S. in biology from George Washington University. In studies on HIV drug resistance and evolution, she used two assays that she developed (Allele-Specific PCR and Ultrasensitive Single-Genome Sequencing) to demonstrate that drug-resistant variants linked on the same viral genomes are associated with antiretroviral therapy (ART) failure. She received NIH Technology Transfer Awards for this work in 2015 and 2016. Valerie is currently investigating the HIV latent reservoir to determine if there is a relationship between the level of methylation of HIV genomes and their levels of expression.
Adam Capoferri, Predoctoral Fellow (Graduate Student)
Adam earned his B.S in biochemistry from Ithaca College. After postbac training at University of Massachusetts Medical School with Dr. Trudy Morrison, he studied HIV dynamics at Johns Hopkins University under Drs. Robert Siliciano and Thomas Quinn. In 2017 Adam received a Young Investigator Scholarship for the Conference on Retroviruses and Opportunistic Infections (CROI). He is now in the Microbiology and Immunology Ph.D. Program at Georgetown University in conjunction with the NIH Graduate Partnership Program. His Ph.D. research includes investigating HIV persistence, evolution, and genetics.
Jennifer Groebner, Ph.D., Postdoctoral Fellow (CRTA)
Jenn earned her Ph.D. in cell and microbial biology from the Catholic University of America in the lab of Dr. Pamela Tuma. In 2016 she won The Benedict T. DeCicco Award for Excellence in Graduate Research. She is currently characterizing HIV-1 provirus expression in T-cell subsets from donors on ART to determine which subsets harbor transcriptionally silent proviruses and which harbor actively transcribed proviruses, a likely source of viremia. In addition to mentoring students in the Kearney lab, Jenn serves as a member of the NIH Fellows Committee and a liaison to the Women Scientists Advisors Committee.
Jenna Hasson, Postbaccalaureate Fellow (CRTA)
Jenna earned her B.A. in biology from Hood College and is currently enrolled in the M.S. Program in Biomedical Science at Hood College. Her research is focused on characterizing HIV-1 proviral genetics in children born with HIV and treated with ART early after birth. Jenna was awarded a Young Investigator Grant to attend the International Workshop on HIV Persistence during Therapy in 2019 and a New Investigator Scholarship to present her research at CROI in 2020.
Mary Grace Katusiime, Ph.D., Postdoctoral Fellow (Visiting)
Mary Grace earned her Ph.D. in medical virology from Stellenbosch University in South Africa under the mentorship of Prof. Gert van Zyl. She was awarded a Margaret McNamara Education Grant in 2018 and a CROI New Investigator Scholarship in 2019. Her research is aimed at describing the persistent HIV-1 reservoir in long-term suppressed, perinatally infected children with a focus on genetically intact viruses, rebound viruses, and immune responses during ART. She is also characterizing proviral integration sites in various cell subsets and proviral decay kinetics in early-treated, long-term suppressed children.
Andrew Musick, M.S., Research Associate II (Contr)
Andrew earned his B.S. in biological chemistry and M.S. in biomedical science with a concentration in virology from Hood College. For his thesis research, he determined levels of HIV proviral expression in infected cell clones detected in people living with HIV. He was awarded CROI Young Investigator Scholarships in 2017 and 2018. In addition, he received the Biomedical Science Faculty Award from Hood College in 2019. Andrew is currently developing a next-generation sequencing assay for near-full-length HIV and performing bioinformatic analysis for the Kearney lab.
Sean Patro, Ph.D., Postdoctoral Fellow (CRTA)
Sean earned his Ph.D. in cell and molecular biology from the University of Pennsylvania under the mentorship of Dr. Luis J. Montaner at the Wistar Institute. His current studies focus on understanding the HIV-1 reservoir during ART, including the size, genetic structure, and host integration location of intact HIV-1 proviruses. Sean published his recent observations of HIV-1 proviral reconstruction in PNAS (116:25891-25899, 2019). In addition to his research, Sean is dedicated to mentoring postbacs and graduate students in the Kearney lab.¬† He was awarded a CROI New Investigator Scholarship in 2020.
Jason W. Rausch, Ph.D., Staff Scientist
Jason received his Ph.D. in biochemistry from Case Western Reserve University. He has been a Staff Scientist for more than 20 years, studying diverse HIV-related topics such as plus-strand priming during reverse transcription, nucleoside analog interference mapping of APOBEC3G substrate specificity, and structural characterization of the viral Rev response element. He is the recipient of three NCI Director‚Äôs Innovation Awards (2007, 2009, 2020) and recently co-authored a successful CCR Technology Development FLEX Award application. Read more about Jason in his CCR investigator profile.
Wei Shao, Ph.D., Programmer/Analyst (Contr)
Wei earned his Ph.D. in molecular biology from the University of Tennessee and M.S. in computer science from Johns Hopkins University. He is a bioinformatics specialist and develops programs, pipelines, tools, and databases that are used by investigators throughout the HIV field. Wei developed and maintains the Retrovirus Integration Database (https://rid.ncifcrf.gov/), Proviral Sequence Database (https://psd.cancer.gov/), and HIVDRLink (https://github.com/Wei-Shao/HIV-DRLin). He received an NCI Group Merit Award in 2016 and a Leidos Outstanding Achievement Award in 2018.
Rachel Sklutuis, Postbaccalaureate Fellow (CRTA)
Rachel earned her B.S. in biology from Towson University and is currently enrolled at Hood College in the M.S. Program in Biomedical Science. Before joining the Kearney lab, she worked on developing and characterizing multivalent influenza virus-like particles at Medigen, assisting with the biomedical company‚Äôs efforts to develop a universal flu vaccine. Rachel is now developing an assay to detect HIV antisense transcripts in people living with HIV and is working to identify sources of continued viremia in individuals on ART by evaluating the levels of HIV-1 RNA expression in subsets of CD4+ T cells.
Jonathan Spindler, Research Biologist
Jon earned his B.S. in nutritional science at the University of Maryland at College Park. In the Kearney lab, he develops new technologies to quantify HIV proviral copy number and levels of proviral expression in single infected cells. He also conducts studies on the characterization of HIV genetics in vivo. In addition to his research, Jon is the lab manager and supervises students in the lab. He received the 2012 NCI Research Group Award and the 2015 NCI Director‚Äôs Award.
Ann Wiegand, M.S., Research Biologist
Ann earned her M.S. degree in biomedical science from Hood College. Early in her career, she developed the HIV Single-Copy Assay (SCA) for measurements of HIV viral load. More recently, Ann contributed to the development of an ultrasensitive method to investigate HIV expression in single cells, and she validated and automated a droplet digital PCR assay to quantify HIV-infected cells in vivo. She received a Federal Technology Transfer Award and an NCI Group Merit Award in 2012.