Frank Maldarelli, M.D., Ph.D.
Frank  Maldarelli, M.D., Ph.D.
Investigator
Head, Clinical Retrovirology Section

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 Drug Resistance Program (DRP), Dr. Maldarelli is an Attending Physician in the NIH NIAID/CCMD HIV Clinic and has established extensive collaborations between the DRP in Frederick and both the NCI HIV and AIDS Malignancy Branch and the NIAID HIV clinical research program in Bethesda.

Areas of Expertise
1) clinical research, 2) HIV drug resistance, 3) antiretroviral therapy, 4) computational biology, 5) infectious diseases, 6) virology

Contact Info

Frank Maldarelli, M.D., Ph.D.
Center for Cancer Research
National Cancer Institute
Building 10, Room 5A06
Bethesda, MD 20892-1403
301-435-8019
fmalli@mail.nih.gov

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.

Scientific Focus Areas:
Clinical Research, Computational Biology, Microbiology and Infectious Diseases, Virology

View Dr. Maldarelli's PubMed Summary.

Selected Key Publications
  1. Maldarelli F, Wu X, Su L, Simonetti FR, Shao W, Hill S, Spindler J, Ferris AL, Mellors JW, Kearney MF, Coffin JM, Hughes SH.
    Science. 345: 179-83, 2014. [ Journal Article ]
  2. Kearney MF, Spindler J, Shao W, Yu S, Anderson EM, O'Shea A, Rehm C, Poethke C, Kovacs N, Mellors JW, Coffin JM, Maldarelli F.
    PLoS Pathog. 10: e1004010, 2014. [ Journal Article ]
  3. Maldarelli F, Kearney M, Palmer S, Stephens R, Mican J, Polis MA, Davey RT, Kovacs J, Shao W, Rock-Kress D, Metcalf JA, Rehm C, Greer SE, Lucey DL, Danley K, Alter H, Mellors JW, Coffin JM.
    J. Virol. 87: 10313-23, 2013. [ Journal Article ]
  4. Josefsson L, Palmer S, Faria NR, Lemey P, Casazza J, Ambrozak D, Kearney M, Shao W, Kottilil S, Sneller M, Mellors J, Coffin JM, Maldarelli F.
    PLoS Pathog. 9: e1003432, 2013. [ Journal Article ]
  5. Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney MF, Proschan MA, Mican JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F.
    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.

Name Position
Elizabeth Anderson Special Volunteer
Jennifer Bell R.N., B.S., C.C.R.C. Protocol Coordinator (Contr)
Giorgio Bozzi M.D. Special Volunteer
Zehava Grossman Ph.D. Guest Researcher (Contr)
Junko Hattori Ph.D. Research Fellow
Shawn Hill M.S., M.B.A. Research Biologist
Charmaine Peters Special Volunteer
Sarah Watters M.Sc. Predoctoral Fellow

Research

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.

Scientific Focus Areas:
Clinical Research, Computational Biology, Microbiology and Infectious Diseases, Virology

Publications

View Dr. Maldarelli's PubMed Summary.

Selected Key Publications
  1. Maldarelli F, Wu X, Su L, Simonetti FR, Shao W, Hill S, Spindler J, Ferris AL, Mellors JW, Kearney MF, Coffin JM, Hughes SH.
    Science. 345: 179-83, 2014. [ Journal Article ]
  2. Kearney MF, Spindler J, Shao W, Yu S, Anderson EM, O'Shea A, Rehm C, Poethke C, Kovacs N, Mellors JW, Coffin JM, Maldarelli F.
    PLoS Pathog. 10: e1004010, 2014. [ Journal Article ]
  3. Maldarelli F, Kearney M, Palmer S, Stephens R, Mican J, Polis MA, Davey RT, Kovacs J, Shao W, Rock-Kress D, Metcalf JA, Rehm C, Greer SE, Lucey DL, Danley K, Alter H, Mellors JW, Coffin JM.
    J. Virol. 87: 10313-23, 2013. [ Journal Article ]
  4. Josefsson L, Palmer S, Faria NR, Lemey P, Casazza J, Ambrozak D, Kearney M, Shao W, Kottilil S, Sneller M, Mellors J, Coffin JM, Maldarelli F.
    PLoS Pathog. 9: e1003432, 2013. [ Journal Article ]
  5. Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney MF, Proschan MA, Mican JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F.
    Proc Natl Acad Sci U S A. 106(23): 9403-8, 2009. [ Journal Article ]

Biography

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.

Team

Name Position
Elizabeth Anderson Special Volunteer
Jennifer Bell R.N., B.S., C.C.R.C. Protocol Coordinator (Contr)
Giorgio Bozzi M.D. Special Volunteer
Zehava Grossman Ph.D. Guest Researcher (Contr)
Junko Hattori Ph.D. Research Fellow
Shawn Hill M.S., M.B.A. Research Biologist
Charmaine Peters Special Volunteer
Sarah Watters M.Sc. Predoctoral Fellow