public health research in

Genomic Epidemiology

The Grubaugh Lab is a collection of academics, professionals, and trainees researching how human and arthropod-borne pathogens evolve over space and time.

LIST OF PUBLICATIONS COMING SOON!

RESEARCH THEMES

In collaboration with the Florida Department of Health, we created phylogenetic models better understand the origin of dengue virus cases in the state.

Taylor-Salmon E, Chew YT, Lopes R, et al. Frequent introductions and climate suitability drive increasing dengue risk in Florida. Medrxiv : the Preprint Server for Health Sciences. 2026 May:2026.05.01.26352185. DOI: 10.64898/2026.05.01.26352185. PMID: 42145607; PMCID: PMC13174716.

OUTBREAK TRACKING

How can we use genomics to understand disease outbreaks?

Genomics is an important tool to track the emergence and spread of viruses. Our laboratory uses targeted and metagenomic sequencing to characterize pathogens from human, animal, and environmental samples. By analyzing how these sequences change across space and time, we can understand the mechanisms behind disease spread and create predictive models to inform public health responses.

Our first research projects aimed to deconstruct the 2016 Zika virus pandemic, investigating its importation to the US. By looking at how the virus’ genome changed over space and time, we were able to identify the sources of Zika infections occurring in the state of Florida.

At the beginning of the SARS-CoV-2 pandemic, we partnered with Yale New Haven Hospital and the CT DPH to surveil the novel SARS-CoV-2 virus in real time. Phylogenetic analysis revealed that new introductions were likely from domestic sources, rather than from international travel, as many were hypothesizing at that point. Sequencing massive numbers of samples also revealed small but consistent nucleotide differences between viral variants, giving us the key to developing a RT-qPCR assay to differentiate between circulating strains.

We continue to respond to new and circulating disease outbreaks, including but not limited to: Dengue Virus, Mycobacterium tuberculois, and Human Monkeypox Virus.


To understand how SARS-CoV-2 control efforts were impacted by viral evolution, we developed a model to correlate amino acid changes in real-world samples to mRNA vaccine efficacy in the same time period.

Kwon J, Li K, Warren JL, Pandya S, Hahn AM, et al. (2026) Utilizing virus genomic surveillance to predict vaccine effectiveness. PLOS Computational Biology 22(5): e1014329. https://doi.org/10.1371/journal.pcbi.1014329

DIVERSITY AND CONTROL

How does genetic diversity impact disease control measures?

Virus evolution and genetic diversity can significantly impact control measures, as demonstrated during the initial COVID-19 vaccine rollout. Vaccine efficacy was significantly effected by emerging viral variants, necessitating boosters to strengthen population-level immunity. As vaccines and other control measures are developed and deployed for other viruses, we continue to evaluate their efficacy in the presence of real-world genomic diversity.

Dengue virus, which has been categorized into four distinct major lineages (serotypes), has withstood many eradication attempts over the decades. Part of the challenge of controlling this virus is effectively targeting the

We are using both experimental and field-based techniques to understand how dengue virus diversity impacts different control strategies.

By exposing Wolbachia-infected mosquitoes to a diverse panel of dengue virus isolates, we identified differences in infection rates between closely-related, but distinct, genetic lineages.




Anne Hahn (left) and Rebecca Earnest (right) prepare materials for field-collecting oral and anal swab samples from field mice and deer. Their work aimed to characterize coronavirus infection in local animal populations.

Earnest, R., Hahn, A.M., Feriancek, N.M. et al. Survey of white-footed mice (Peromyscus leucopus) in Connecticut, USA reveals low SARS-CoV-2 seroprevalence and infection with divergent betacoronaviruses. npj Viruses 1, 10 (2023). https://doi.org/10.1038/s44298-023-00010-4

GENOMIC ECOLOGY
How does the environment effect pathogen evolution and transmission?

Mosquito and tick-borne viruses have complex ecologies which can define the speed and range of their spread. Several years ago, we started the WestNile4K project to sequence West Nile virus from throughout the Americas to better define “transmission zones” and the ecological barriers that define them. Our work revealed how the virus initially spread across the US and its evolution into distinct lineages.

A similar sequencing and phylogenetic study on the tick-borne Powassan Virus traced its (re)emergence into the Northeast US and revealed that transmission is limited to tight geographical foci.


Isa Gamez loads a DNA library into a nanopore flowcell. Using the MinION benchtop sequencer, we are able to quickly analyze pathogen genomes and workshop new protocols.

METHODS DEVELOPMENT

What tools are needed to best answer our research questions?

There are many challenges to working in genomic epidemiology. Viruses and bacteria evolve rapidly, and so does the technology. We are always on lookout for new tools and analysis methods, but must often create these resources for ourselves.

PrimalSeq, a technique for developing tiles amplicon DNA libraries, enables us to design custom primer schemes for developing whole genome viral sequencing assays. We have used this tool to create assays for amplifying RSV, hMPV, WNV, and DENV 1 – 4, and others. In developing a panel for Jamestown Canyon Virus using the PrimalSeq method, we found that a modified experimental design was needed for amplifying multi-segmented viruses.

We are currently exploring how amplicon-based sequencing of M. tuberculosis can be used to rapidly identify antimicrobial resistant alleles, which required the design of a massively-multiplexed PCR and specialized analysis pipelines. These methods continue to be optimized as we update the assay and optimize its use on different sequencing platforms.

While our work has direct public health implications, our research findings do not constitute as medical advice.
For background information regarding the organisms and diseases that we study, we ask that you refer to:

Centers for Disease Control and Prevention
World Health Organization

THIS research IS made possible THANKS TO our funding sources:

AgencyID#TitlePrincipal InvestigatorFunding StartFunding End
NIH/NIAIDDP2 AI176740-01Enhancing dengue virus genomic surveillance to uncover circulating genetic diversityNathan Grubaugh9/21/20228/31/2027
CDC (administered by Massachusetts Department of Health)1 NU50CK000629-01-00New England Pathogen Genomics Center of ExcellenceShirlee Wohl9/30/20229/29/2026
NIH/NIAID1R01AI179874-01Real-World Effectiveness of Perinatal RSV ImmunoprophylaxisCarlos Oliveira12/8/202310/31/2028
Yale Planetary SolutionsAcceleration GrantClimate-driven global expansion of dengue endemicityNathan Grubaugh5/1/202510/30/2026
The Ambrose Monell Foundation (administered by YSPH)Faculty seed grantAdaptive potential and dynamics of West Nile virus lineagesNathan Grubaugh, Chantal Vogels5/1/20264/30/2027
NIH/NIAID1R01AI195985-01Serotype re-emergence and vaccine impact in the era of next-generation pneumococcal vaccinesDan Weinberger4/1/20263/31/2031
MerckMISP #103622Use of genomic and EHR data to infer the diversity and burden of circulating RSV strains in young children and in older adultsVirginia Pitzer4/1/20264/1/2027
MerckMISP #103595Genomic surveillance to uncover local dynamics of co-circulating HMPV and RSVNathan Grubaugh4/1/20264/1/2027
NIH/NIAID5R01AI180209-02Evolution, transmission, and control of drug-resistant tuberculosisNathan Grubaugh5/1/202604/31/2029