Frank Maldarelli, M.D., Ph.D.
Dr. Maldarelli heads the Clinical Retrovirology Section, which develops and implements clinical protocols to elucidate mechanisms underlying the emergence of HIV drug resistance in vivo, the dynamics of infection under treatment, and the role of resistance mutations in the efficacy and failure of subsequent treatments. Representing the clinical research arm of the HIV Dynamics and Replication Program (HIV DRP), Dr. Maldarelli is an Attending Physician in the NIH NIAID/CCMD HIV Clinic and has established extensive collaborations between the HIV DRP in Frederick and both the NCI HIV and AIDS Malignancy Branch and the NIAID HIV clinical research program in Bethesda.
Clinical Studies on HIV Resistance
The Clinical Retrovirology Section develops and implements clinical protocols to elucidate mechanisms underlying the emergence of resistance in vivo, the dynamics of infection under treatment, and the role of resistance mutations in the efficacy and failure of subsequent treatments.
In the first of four projects conducted by the Clinical Retrovirology Section, our goal is to determine the dynamics of viral replication in HIV-infected patients on suppressive antiretroviral therapy. These studies are being extended in clinical trials performed at NIH and elsewhere to determine the levels of viremia when treatment regimens are either simplified or intensified. We are also exploring new strategies to decrease reservoirs of HIV-1 in infected individuals.
In a second research project, we are investigating the genetic structure of HIV populations in infected individuals. We are using the single-genome sequencing technology developed by the Translational Research Unit to analyze and understand the accumulation of genetic variation in the gag/pol and env genes of HIV-1 in a number of different patient groups, including chronically infected patients, both naive and on therapy, as well as in primary and early HIV-1 infection. We are complementing existing single-genome sequencing and allele-specific PCR assays with next-generation sequencing and new single-cell assays for cell associated HIV RNA and DNA. We are determining precise estimates of the roles of population size, genetic drift, selection, and recombination in shaping HIV populations. The goal of this study is to understand the nature of the forces (mutation, selection, drift, recombination) that mold the genetic diversity of virus populations before and after antiretroviral therapy is introduced.
The third project is focused on elucidating the mechanisms of persistent viremia in vivo. We are conducting clinical trials of targeted interventions to characterize HIV reservoirs in individuals suppressed on ART. We are determining the role of generalized immune activation and GALT on persistence using nonabsorbable antibiotics to specifically reduce gut bacteria, and studying the effects of specific antigenic activation on HIV using immunization and sampling protocols. We are also investigating the role of target cell number on HIV reservoirs by studying the effects of cytotoxic chemotherapeutics on HIV viremia, and we are investigating the role of innate immunity in HIV persistence by studying the effects of the innate immune modulator interferon alpha 2b.
Selected Key Publications
- Proc. Natl. Acad. Sci. USA. 113: 1883-1888, 2016. [ Journal Article ]
HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells.Science. 345: 179-83, 2014. [ Journal Article ]
- PLoS Pathog. 10: e1004010, 2014. [ Journal Article ]
- J. Virol. 87: 10313-23, 2013. [ Journal Article ]
Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy.Proc Natl Acad Sci U S A. 106(23): 9403-8, 2009. [ Journal Article ]
Dr. Frank Maldarelli received his Ph.D. from the City University of New York and his M.D. from Mount Sinai School of Medicine. After completing his residency in internal medicine at The Columbia-Presbyterian Hospital, New York, he joined the Laboratory of Molecular Microbiology at the National Institute of Allergy and Infectious Diseases (NIAID) as a Medical Staff Fellow. In 1998, Dr. Maldarelli joined the HIV Drug Resistance Program (HIV DRP, renamed as the HIV Dynamics and Replication Program in 2015) in the National Cancer Institute (NCI) as Head of the In Vivo Biology Group, which was later renamed the Clinical Retrovirology Section. He was promoted to Tenure-Track Investigator in 2012. Representing the clinical research arm of the HIV DRP, he has established extensive collaborations between the HIV DRP in Frederick and both the NCI HIV and AIDS Malignancy Branch and the NIAID AIDS clinical research program in Bethesda. Dr. Maldarelli is an Attending Physician in the NIAID/CCMD HIV service, and is currently a member of the NIH Infectious Disease Advisory Board, the Scientific Advisory Committee of the American Federation for AIDS Research, and the Review Panel for the Henry M. Jackson Foundation for the Advancement of Military Medicine. He has recently served as a faculty member of the International Society of Infectious Diseases HIV Training Program, NIH Infectious Disease Consult Service, and Center for Bio-Medical Communications Infectious Disease Board Review Course, and as a lecturer in the Washington D.C. community outreach PACT Program.
|Elizabeth Anderson||Predoctoral Fellow (Graduate Student)|
|Jennifer Bell R.N., B.S., C.C.R.C.||Protocol Nurse Coordinator II (Contr)|
|Zehava Grossman Ph.D.||Scientist (Contr)|
|Pamela Jo Harris M.D.||Physician (Contr)|
|Shawn Hill M.S., M.B.A.||Research Biologist|
|Kristi Huik Ph.D.||Postdoctoral Fellow (Visiting)|
|Camille Lange Ph.D.||Postdoctoral Fellow (Visiting)|
|Paula Rote||Predoctoral Fellow (Graduate Student)|
Young Investigator Awards, Conference on Retroviruses and Opportunistic Infections
Elizabeth Anderson and Camille Lange received Young Investigator Awards to present their research findings at the 2017 Conference on Retroviruses and Opportunistic Infections. This highly selective travel scholarship is awarded to postdoctoral fellows and students whose abstracts are accepted for presentation at the conference.
Diversity Career Development Program, NIH
Camille Lange graduated from the Diversity Career Development Program (DCDP) at NIH in 2016. DCDP graduates were nominated and selected among a group of talented NIH staff for participation in this program.
Scholarship Award, 2016 Towards an HIV Cure Symposium and 21st International AIDS Conference (AIDS 2016)
Elizabeth Anderson was awarded a scholarship to attend the 2016 Towards an HIV Cure Symposium and the 21st International AIDS Conference (AIDS 2016) in Durban, South Africa. She presented the latest findings of her research project ("Intra-patient, full length analysis of HIV gag genetic variation identifies regions of variability") at both meetings.
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.).
Travel Award, HIV DRP Think Tank Meeting
Francesco Simonetti received a $1000 travel award (provided by the Center of Excellence in HIV/AIDS & Cancer Virology, Center for Cancer Research, NCI) for presenting one of the two most meritorious talks by NCI fellows at the 2014 HIV DRP Think Tank Meeting.
NIH Postbac Poster Day Award
Tiffany Tanzosh was honored for presenting one of the best posters on NIH Postbac Poster Day in 2012. Established in 2001, NIH Postbac Poster Day added a judging component in 2011 to highlight the contributions of postbaccalaureate fellows to the NIH Intramural Research Program. Awardees are recognized for having authored posters that score in the top 20% of all posters presented.