Dave Rasko Laboratory
The Rasko Laboratory was established in July 2008 and is dedicated to the study of pathogenic bacteria through comprehensive genomic analysis. Our research emphasizes the molecular mechanisms of pathogenesis with the goal of informing the development of novel therapeutics and diagnostic tools. We are an integral part of the collaborative research environment at the Institute for Genome Sciences (IGS), within the University of Maryland School of Medicine.
GCID
A project currently funded in the laboratory is under the Genomic Centers for Infectious Diseases (U19) awarded to the Institute for Genome Sciences at the University of Maryland entitled the “Host, Pathogen, and the Microbiome: Determinants of Infectious Disease Outcomes”. The Rasko lab has a leading role in the Microbial Project titled “Examination of Enteric Pathogens with Multi-Omic Approaches” where we are examining the pathogen populations, microbiome and metagenomic and metatranscriptomic samples from two human challenge studies that were conducted at the University of Maryland on either enterotoxigenic E. coli or Vibrio cholerae. These will be some of the first studies to examine these pathogens in samples from humans to directly examine the impact of these pathogens on the microbiome and hosts.
Please refer to the website on the IGS homepage for descriptions of other projects and available data.
ETEC
The Rasko lab has been working on enterotoxigenic E. coli (ETEC) since its inception in 2008, and even before that with the publishing of the first and second ETEC genomes, E24377a and B7A in 2008 (Rasko I&I, 2008). Those initial studies were extended in 2011 to include a number of additional ETEC references (Sahl et al, I&I, 2011) and further extended in collaborative projects with the Wellcome Trust Sanger Institute which resulted in a publication in Nature Genetics by von Mentzer et al. Further work on the genomics of ETEC in a collection from Bangladesh identified that multiple isolates can be identified in individual subjects, resulting in it being very difficult to assign which isolate may be the actual etiological agent. The paper describing this variation can be found here.
We are continuing to examine the variation among ETEC isolates from human samples, see the description of the GCID project above. Within that project we have the opportunity to examine variation as the pathogen travels through the host. This work is underway and stay tuned for future publications.
AEECs (EPEC & EHEC)
In 2013 we published a study describing the genomes of 114 attaching and effacing E. coli (AEEC) in PNAS that can be found here. This study included newly sequenced genomes of enteropathogenic E. coli (EPEC) and also O157:H7 and non-O157 enterohemorrhagic E. coli (EHEC). Also, as an aim of the UMB ERIN CRC Project lead by Dr. James Kaper we investigated the genomic diversity of typical EPEC from study sites in the Global Enteric Multicenter Study (GEMS). This resulted in a manuscript published in Nature Microbiology in 2016, located here. Following these studies we used comparative genomics to investigate the diversity of the AEEC virulence plasmids in a study that can be found here.
EIEC
The Rasko Lab, in collaboration with researchers at the FDA and University of Florida, recently published a paper describing enteroinvasive E. coli (EIEC) genomes compared with representative Shigella genomes. This analysis identified three distinct clades of EIEC that can be used as references of EIEC genome diversity. The paper can be found here.
Shigella
Shigella species isolates have long been suggested to be close relatives to E. coli. We demonstrated in a paper by Sahl et al. that Shigella isolates have evolved from E. coli in approximately 3 radiations, but not necessarily only three times. The genomic differences in global collections of Shigella isolates were cataloged and could be used as a molecular diagnostic for the Shigella species into different genomic groups.
We also recently characterized a collection of S. boydii genomes, which had not been examined in detail previously. The majority of those isolates were obtained from the Global Enteric Multicenter Study (GEMS) collection and to date represent the largest collection of S. boydii isolates to be examined. The paper can be found here.
In addition to the genomic comparisons we also demonstrated the utility of combining genomics and transcriptomics into the study of the pathogenesis of these organisms. We identified genes that were genomically common in the S. flexneri and expressed in a series of microarray and RNA-seq experiments. This gene was identified as a growth regulator and was characterized though classic microbial pathogenesis and identified to be a negative regulator of multiple virulence genes and pathways. This important paper can be found here.
Ongoing Shigella work includes the further examination of isolates from the Global Enteric Multicenter Study (GEMS) sites and comparative genomics and transcriptomics among the isolates of this important human pathogen.
Antimicrobial Resistance
As with many other groups we have expanded our studies onto the global problem of antimicrobial resistance. Our early genomic studies have focused on Klebsiella species and their evolution, as well as a collection of >200 Acinetobacter baumannii isolates from the University of Maryland Medical Center. These papers can be found on the publications pages here.
Additional transcriptional and functional studies are being followed up on in the lab. Stay tuned for future publications on these topics.
Laboratory Personnel
Dave Rasko, PhD
Bernadette Hritzo
Bernadette Hritzo
Assistant Professor, Principal Investigator
I am a Professor in the Department of Microbial Pathogenesis and a member of the Institute for Genome Sciences. During my career I have developed expertise in comparative microbial genomics, bioinformatics and functional genomics. I have led comparative genome sequencing and analysis projects fo
Assistant Professor, Principal Investigator
I am a Professor in the Department of Microbial Pathogenesis and a member of the Institute for Genome Sciences. During my career I have developed expertise in comparative microbial genomics, bioinformatics and functional genomics. I have led comparative genome sequencing and analysis projects for important human diarrheal pathogens, focusing on Escherichia coli and Shigella species as well as Bacillus cereus group isolates. I have developed comparative bioinformatics tools designed to characterize the genetic diversity in closely related bacterial isolates. Also, I was the first to publish a comparative genomic study that included a genome reference from a true commensal, each of the six diarrheagenic E. coli pathogenic variants (pathovars) as well as representatives of the urinary tract and avian derived E. coli to total 17 genomes. This resulted in the first description of the E. coli pangenome as “open” and identified a core gene set of ~2200 genes present in all E. coli. This comparative work has laid the framework for the continued functional study of the evolution of these pathogens, which has recently been expanded to include Shigella spp., as well as functional studies of these unique and conserved gene features.
Past Members
Michael Sikorski – Graduate Student
Tracy H. Hazen, Ph.D. – Research Associate
Taylor Richter, Ph.D. – Post Doctoral Fellow
Lanie Wallace – Graduate Student
Jason W. Sahl, Ph.D. – Post Doctoral Fellow
Susan R. Leonard (aka Susan Steyert), Ph.D. – Post Doctoral Fellow
Julia C. Redman – Lab manager
Carolyn R. Morris – Ph.D. Graduate Student
Jeticia Sistrunk – Ph.D. Graduate Student
Dane Kania – M.S. Graduate Student
Past Rotation Students
Jing Han – Graduate Student
Jennifer Emberger – M.D. Student
Lauren Hittle – Ph.D. Graduate Student
Justin Taylor – Ph.D. Graduate Student
Alexandria Reinhardt – Ph.D. Graduate Student
Emily Flowers – Ph.D. Graduate Student