Frank Maldarelli, M.D., Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 535, Room 108E
- Frederick, MD 21702-1201
- 301-846-5611
- fmalli@mail.nih.gov
RESEARCH SUMMARY
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.
Areas of Expertise
Frank Maldarelli, M.D., Ph.D.
Research
Clinical Studies of HIV Drug Resistance
The Clinical Retrovirology Section 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.
In the first of three 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 (ART). 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 Section 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 ART 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 gut-associated lymphoid tissue (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.
Publications
Dynamic shifts in the HIV proviral landscape during long term combination antiretroviral therapy: Implications for persistence and control of HIV infections
Combined HIV-1 sequence and integration site analysis informs viral dynamics and allows reconstruction of replicating viral ancestors
No evidence of ongoing HIV replication or compartmentalization in tissues during combination antiretroviral therapy: Implications for HIV eradication
Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo
HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells
Biography
Frank Maldarelli, M.D., Ph.D.
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 the HIV Dynamics and Replication Program in 2015) in the National Cancer Institute (NCI) as a Staff Clinician and Head of the In Vivo Biology Group, which was later renamed the Clinical Retrovirology Section. In 2012 he was appointed as a Tenure-Track Investigator, and he was promoted to a tenured Senior Investigator position in 2018. Representing the clinical research arm of the HIV DRP, Dr. Maldarelli 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. He is an Attending Physician in the NIAID/CCMD HIV service, the NCI Liaison to the Leidos HIV Molecular Monitoring Core, and a Scientific Committee Member of the International Workshop on HIV Drug Resistance. He served on the NIAID Institutional Review Board (as Chair and Vice-Chair), NIH Infectious Disease Advisory Board, Scientific Advisory Committee of the American Federation for AIDS Research, and Review Panel for the Henry M. Jackson Foundation for the Advancement of Military Medicine. He was 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 a lecturer in the Washington D.C. community outreach PACT Program. His awards include the NCI Leading Diversity Award in 2010, NIH Director’s Group Award in 2015, Center for Cancer Research (CCR) Group Award in 2016, and multiple Staff Recognition, NIH Bench-to-Bedside, and Intramural AIDS Targeted Antiviral Program (IATAP) awards. Dr. Maldarelli is a member of a number of committees, and he chairs the CCR Non Human Primate Scientific Review Committee, Data Safety Monitoring Board for the GRAVITY Study, and Tenure Track Selection Committee for Critical Care Medicine. He currently serves on the Editorial Board of the Journal of Virology.
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Team
News
New Investigator Scholarships, Conference on Retroviruses and Opportunistic Infections
Kristi Huik was awarded a New Investigator Scholarship to present her research findings in the 2020 Conference on Retroviruses and Opportunistic Infections (CROI). CROI scholarship awardees in previous years include Elizabeth Anderson and Camille Lange in 2018 and 2017, Sarah Watters in 2015, and Francesco Simonetti in 2014.
2019 Presentation Award in Microbiology, Annual Biomedical Research Conference for Minority Students
Natalie Lindo received a 2019 Presentation Award in Microbiology for presenting her research findings at the Annual Biomedical Research Conference for Minority Students.
Scholarship Award, International Workshop on HIV Drug Resistance and Treatment Strategies
Kristi Huik was awarded a scholarship to attend the 2018 International Workshop on HIV Drug Resistance and Treatment Strategies in Johannesburg, South Africa, to give an oral presentation on the latest findings of her research project ("Mechanism of Emergence of Resistance of T97A during Dolutegravir Therapy").
Young Scientist Sponsorship, 68th Lindau Nobel Laureate Meeting
Kristi Huik was awarded a full sponsorship by the Estonian Academy of Sciences to participate in the 68th Lindau Nobel Laureate Meeting in June 2018. She received this award based on her outstanding research on the role of host genetic factors in HIV acquisition, HIV drug resistance, and molecular epidemiology of other infections while she was a Ph.D. student at the University of Tartu before joining the Maldarelli lab. The annual Lindau Nobel Laureate Meeting is a prestigious gathering of around 30 Nobel Laureates and 500-600 young scientists — including postdoctoral fellows, Ph.D. students, and undergraduates — who convene to communicate leading issues in physiology and medicine in a forum that includes lectures, panel discussions, poster sessions, master classes, Agora talks, and science walks.
Travel Awards, HIV DRP Think Tank Meeting
Elizabeth Anderson received a $1000 travel award from the HIV DRP for one of the two best presentations by NCI fellows at the 2018 HIV DRP Think Tank Meeting. Francesco Simonetti received this Travel Award for his presentation at the 2014 HIV DRP Think Tank Meeting.
Travel Award, Fall HIV/AIDS & Cancer Virology Think Tank Meeting
Paula Rote won a $1000 travel award for her outstanding talk at the 2017 Fall HIV/AIDS & Cancer Virology Think Tank Meeting. This annual Think Tank meeting on the NIH-Bethesda campus provides a venue for students, postdoctoral fellows, and staff scientists to present emerging work and hypotheses in the field of cancer virology. The Think Tank travel awards are provided by the Center of Excellence in HIV/AIDS & Cancer Virology, Center for Cancer Research, NCI.
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.).
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.