Bacterial pathogens may undergo dramatic evolution in the context of chronic infection, facilitating host adaptation and the development of antibiotic resistance. In some cases, elevated mutation rates due to evolved mismatch repair and proofreading deficiencies have been shown to contribute to accelerate this evolution. An important insight from studies of within-host adaptation has been that genetic modifications that occur during chronic infection may parallel those that underlie the emergence of human-restricted pathogens from broad-host range generalists over longer evolutionary periods. In the BPARU, we apply a systems biology approach to understand selection dynamics and host-pathogen interactions in the context of defined genetic immunodeficiency diseases. This approach integrates genomics, transcriptomics (RNA-seq), and metabolomic methods to identify and characterize specializations that occur during within-host adaptation. In these studies, we seek to address (1) the role of bacterial hypermutation and other forms of genome plasticity in within-host evolution, (2) the roles that host immune deficiencies can play in shaping the within-host evolution in persistent infections, and (3) the evolution of antimicrobial resistance in the context of acute and chronic infection.
Another linked area of focus within the BPARU are the evolutionary mechanisms by which antibiotic resistance emerges in Gram-negative bacterial pathogens in the context of acute and chronic infection. The approaches applied include genomic sequencing of current and historical clinical bacterial isolates, transcriptome analysis with RNA-seq, proteomics, metabolomics, and in vitro adaptive evolution. This work aims to reveal novel mechanisms of resistance to broad spectrum antibiotics, with implications for clinical treatment of Gram-negative infections.
John P. Dekker, M.D., Ph.D., FCAP
Lasker Clinical Research Scholar
Chief, Bacterial Pathogenesis and Antimicrobial Resistance Unit
Director, Genomics Section, Microbiology Service, Department of Laboratory Medicine, NIH Clinical Center
Specialty(s): Pathology, Clinical, Pathology, Medical Microbiology
M.D., Harvard Medical School
Ph.D., Harvard University
Augusto Dulanto Chiang, M.D. (He/Him/His)
Assistant Research Physician
Specialty(s): Infectious Disease, Internal Medicine Provides direct clinical care to patients at NIH Clinical Center
Infectious Diseases Fellowship and Advanced Infectious Diseases and Genomics Fellowship, 2019, NIAID
Internal Medicine Residency, Washington Hospital Center
M.D., 2011, Cayetano Heredia University, Lima
Languages Spoken: Spanish
Jessie Ellis, Ph.D. (She/Her/Hers)
Ph.D., Tufts University
Soma Ghosh, Ph.D. (She/Her/Hers)
Staff Scientist, Laboratory of Clinical Immunology and Microbiology
Ph.D., 2015, Indian Institute of Science, Bangalore, India
Languages Spoken: Hindi, Bengali
Abraham (Jon) Moller, Ph.D. (He/Him/His)
Ph.D., Microbiology and Molecular Genetics (MMG), 2021, Emory University
M.S., Cell, Molecular, and Structural Biology (CMSB); B.A., Chemistry; B.S., Microbiology, 2016, Miami University (Ohio)
Prashant Prabhakar Patil, Ph.D. (He/Him/His)
Languages Spoken: Hindi
Former Research Group Members
Jung-Ho Youn, Ph.D.
Department of Laboratory Medicine
NIH Clinical Center
Jonathan Ho, M.D.
Internal Medicine Resident
Brown University, RI
Jamie Lemon, Ph.D.
Director of Infectious Disease Diagnostics
Northwell Health Laboratories
New York, NY
Andrew Clark, Ph.D.
UT Southwestern Medical Center
Derek N. Smith, Ph.D.
Environment and Climate Change Canada
Government of Canada
Lidia Beka, Ph.D.
Technology Transfer Center
National Cancer Institute
Chao-Jung Wu, Ph.D.
Taipei Medical University
Mike Tisza, Ph.D.
Baylor College of Medicine
Adrien Launay, Ph.D.