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 Bacterial Pathogenesis and Antimicrobial Resistance Section (BPARS), 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 BPARS 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.
Senior Investigator
Lasker Clinical Research Scholar
Chief, Bacterial Pathogenesis and Antimicrobial Resistance Section
Specialty(s): Pathology, Clinical, Pathology, Medical Microbiology
Education:
M.D., Harvard Medical School
Ph.D., Harvard University
Dr. Dekker received his M.D. from Harvard Medical School and Ph.D. from Harvard University through the NIH Medical Scientist Training Program. He completed pathology residency and fellowship training in medical microbiology at Massachusetts General Hospital and is board-certified in clinical pathology and medical microbiology through the American Board of Pathology. In 2013, he joined the NIH...
Soma Ghosh, Ph.D.
Staff Scientist
Education:
Ph.D., 2015, Indian Institute of Science, Bangalore, India
Languages Spoken: Hindi, Bengali
Dr. Ghosh received her Ph.D. in 2015 from the Indian Institute of Science, Bangalore, India, where she used Systems Biology approaches to study host-pathogen interactions in the context of iron acquisition by M. tuberculosis. She joined Johns Hopkins University, Baltimore, in 2015 as a postdoctoral research fellow with Dr. Tamara O’Connor in the department of biological chemistry. There, she...
Grace Morales, Ph.D.
Postdoctoral IRTA Fellow
Education:
Ph.D., 2024, Vanderbilt University, Nashville, TN
Dr. Morales received her Ph.D. in 2024 from Vanderbilt University. Her work was largely focused on connecting microbial genotypes to clinical phenotypes, with an emphasis on uropathogenic E. coli and the development of UTI and asymptomatic bacteriuria. This work employed a combination of genomics and host-pathogen interaction work in the context of UTIs. Dr. Morales joined BPARS in October 2024...
Prashant Prabhakar Patil, Ph.D.
Postdoctoral Fellow
Languages Spoken: Hindi
Alexander Sastokas, B.S.
Postbaccalaureate IRTA Fellow
Education:
B.S., 2025, Arizona State University, Tempe, AZ
Alexander Sastokas joined the BPARS as a Postbaccalaureate IRTA fellow in August 2025. He is using a combination of genomic, metabolomic, and phenotypic approaches to study clonal evolution in a set of clinical Burkholderia vietnamiensis isolates to understand host adaptation.
Rahul Sehgal, B.S.
Postbaccalaureate IRTA Fellow
Education:
B.S., 2024, University of California San Diego, La Jolla, CA
Rahul Sehgal joined the BPARS as a Postbaccalaureate IRTA Fellow in September 2025. His research focuses on investigating antibiotic resistance in clinical Bacteroides fragilis isolates mediated by epigenetic mechanisms, including DNA methylation. He brings prior research experience with single-cell RNA sequencing and is currently using Oxford Nanopore and Illumina short-read sequencing approaches...
Nick Vereecke, Ph.D., ir.
Postdoctoral Visiting Fellow
Education:
Ph.D., 2023, Ghent University, Ghent, Belgium
Languages Spoken: Dutch, French
Dr. Vereecke received his Ph.D. in 2023 from Ghent University, Ghent, Belgium, where he studied the use of long-read sequencing for viral and bacterial diagnostics in veterinary medicine. While his work focused on sequencing-driven diagnostics, it also shed new light on the use of genomics in the context of antimicrobial resistance in Mycoplasmopsis bovis, Brachyspira hyodysenteriae, and...
Former Research Group Members
- Jung-Ho Youn, Ph.D., Genomics Scientist, Department of Laboratory Medicine, NIH Clinical Center
- Jonathan Ho, M.D., Attending Physician, Brown Health, Rhode Island
- Jamie Lemon, Ph.D., Director of Infectious Disease Diagnostics, Northwell Health Laboratories, New York, New York
- Andrew Clark, Ph.D., Assistant Professor, UT Southwestern Medical Center, Dallas, Texas
- Derek N. Smith, Ph.D., Genomics Biologist
- 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., Assistant Professor, Baylor College of Medicine, Houston, Texas
- Adrien Launay, Ph.D., Chief, Bioinformatics, Endogenomiks, Mexico
- Augusto Dulanto Chiang, M.D., Assistant Professor, Vanderbilt University Medical Center, Vanderbilt, Tennessee
- Abraham (Jon) Moller, Ph.D., Bioinformatics System Analyst, CARD, NIA, NIH
- Jessie Ellis, Ph.D., Scientist III, The HNRCA at Tufts University, Boston, Massachusetts
- Arthi Ramkumar, B.S., Clinical Research Coordinator, Brigham and Women’s Hospital, Boston, Massachusetts
- Tommy Yoon, B.A., graduate student, Cornell University, New York