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
Education:
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
Education:
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
Dr. Dulanto Chiang obtained his M.D. in 2011 from the Cayetano Heredia University in Lima, Peru, after which he completed an internal medicine residency at Washington Hospital Center followed by an Infectious Diseases Fellowship and Advanced Infectious Diseases and Genomics Fellowship at NIAID.
Jessie Ellis, Ph.D. (She/Her/Hers)
Post-Doctoral Fellow
Education:
Ph.D., Tufts University
Soma Ghosh, Ph.D. (She/Her/Hers)
Staff Scientist, Laboratory of Clinical Immunology and Microbiology
Education:
Ph.D., 2015, Indian Institute of Science, Bangalore, India
Languages Spoken: Hindi, Bengali
Abraham (Jon) Moller, Ph.D. (He/Him/His)
Post-Doctoral Fellow
Education:
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)
Dr. Moller’s research in the BPARU focuses on understanding within-host evolution of Gram-negative opportunistic pathogens through population genomic and evolutionary biological approaches.
Prashant Prabhakar Patil, Ph.D. (He/Him/His)
Post-Doctoral Fellow
Languages Spoken: Hindi
Dr. Patil’s research in the BPARU focuses on novel mechanisms of resistance to advanced generation cephalosporins and cephalosporin beta-lactam inhibitor combination antibiotics in P. aeruginosa. These questions are investigated with a combination of in vitro adaptive evolution, genetic engineering, genomic sequencing, gene expression analysis with RNA-seq, and analysis of clinical isolates.
Former Research Group Members
Jung-Ho Youn, Ph.D.
Genomics Scientist
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.
Assistant Professor
UT Southwestern Medical Center
Dallas, TX
Derek N. Smith, Ph.D.
Genomics Biologist
Environment and Climate Change Canada
Government of Canada
Lidia Beka, Ph.D.
Technology Transfer Center
National Cancer Institute
Chao-Jung Wu, Ph.D.
Assistant Professor
Taipei Medical University
Taiwan
Mike Tisza, Ph.D.
Bioinformatics Scientist
Baylor College of Medicine
Houston, TX
Adrien Launay, Ph.D.
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