Louise H. Moncla, PhD, is an assistant professor in the Department of Pathobiology who started her lab in September 2022. Dr. Moncla performed her undergraduate studies at Penn State University, where she received bachelor’s degrees in biology and music (trumpet performance). During her undergraduate research, Dr. Moncla worked with Dr. Beth Shapiro to study polar bear evolution. While classified as distinct species, polar bears and brown bears increasingly interact due to climate change and receding sea ice, and opportunistically mate to produce fertile offspring (dubbed “grolars” or “pizzlies”). Some evidence suggests that polar bears and brown bears may have intermixed during ancient periods of deglaciation, providing a mechanism by which polar bear diversity could be maintained during climate stress. During her undergraduate research, Dr. Moncla isolated and sequenced nuclear genes from polar bears and brown bears sampled near Alaska and built phylogenetic trees to infer the evolutionary relationship between these two species. This experience introduced Dr. Moncla to research and led her to pursue a PhD in microbiology.
Dr. Moncla completed a PhD at the University of Wisconsin-Madison under the mentorship of Dr. Thomas Friedrich. Her PhD work focused on developing methods for generating and analyzing next-generation sequencing data to understand viral within-host diversity and the ways that transmission bottlenecks influence viral evolution. RNA viruses have short generation times, large population sizes, and high mutation rates, allowing them to rapidly diversify within individual, infected hosts. Dr. Moncla and her colleagues pioneered early work showing that antigenic variants may arise during seasonal influenza infections but fail to become fixed. In a separate study that traced the evolution of an avian influenza virus as it adapted to mammals, Dr. Moncla discovered that selection on the receptor binding protein was critical for avian influenza virus replication and transmission and that transmission bottlenecks may propagate host-adapting mutations. This work resulted in an Institut Pasteur Young Investigator Award, launching a collaborative project to characterize how avian influenza viruses evolve within naturally infected humans and domestic birds in Cambodia.
Carrying this project into her postdoc with Dr. Trevor Bedford (Fred Hutchinson Cancer Center), Dr. Moncla worked to combine within-host diversity metrics with new analytic approaches from phylogenetics to understand how viruses evolve and transmit across host groups. By characterizing how highly pathogenic avian influenza viruses evolve during natural infections, she showed that these viruses generate human-adapting mutations during natural spillover infections, but that these mutations stayed at low frequencies within-host and were absent from many human infections (Moncla et al, PLOS Pathogens, 2020). Together, these results showed that our understanding of the genetic factors that drive human infection is poorly understood. To fill these gaps in knowledge, Dr. Moncla developed a public visualization of global avian influenza virus evolution and circulation built on the Nextstrain platform and hosted on Nextstrain.org/flu/avian. Dr. Moncla curated ~20,000 genomes sampled globally from 1996 to the present, from a broad range of host species, and developed additional visualizations that show pathogenicity determinants, genetic classifications, and epidemiologically relevant metadata. Dr. Moncla updates this website monthly to provide real-time data on global avian influenza evolution and transmission patterns, which has been particularly useful during the ongoing avian influenza outbreak in North America. Dr. Moncla plans to continue developing new features for this website in her new lab.
With this resource and dataset in place, and funding from a Life Sciences Research Foundation postdoctoral fellowship and a K99/R00 Pathway to Independence Award, Dr. Moncla began working on the genetic and ecological factors that drive avian influenza cross-species transmission. Avian influenza viruses naturally circulate in wild, migratory birds, but can become endemic in domestic bird populations, where they facilitate sporadic human infections. When humans are infected with these viruses, case fatality rates can be as high as 60%. In 2021, these viruses were introduced into North America, sparking an uncontrolled outbreak in which hundreds of thousands of wild birds have died, nearly 60 million domestic birds have been culled, and mammals have been infected (foxes, stone martens, mink, seals, sea lion, and three humans) at an unprecedented rate. These developments highlight the need to better understand the factors driving transmission and how to evaluate the risk these viruses pose to humans. Towards this end, the Moncla lab is now working to develop novel, genomic approaches to identify mutations that enhance the likelihood of mammal infection, which can then be phenotypically validated in the lab. This work could allow us to better understand the risk that currently circulating viruses pose to humans. Others in the group are leading work to use novel phylogenetic models to reconstruct how these viruses have evolved historically, and the role that distinct classes of birds have played in driving transmission. By partnering with Drs. Lisa Murphy and Eman Anis in the Avian Diagnostic Laboratory at New Bolton Center, the Moncla lab is now sampling and sequencing viruses from positive birds and mammals in Pennsylvania to reconstruct transmission patterns locally and nationally. These studies are critical for designing surveillance and outbreak response strategies, and for prioritizing populations to target for vaccination.
In addition to her work on avian influenza, Dr. Moncla is also broadly interested in using viral genomics to reconstruct viral outbreaks. In 2019, through a collaborative project with the Colombian NIH, she showed that the Zika virus epidemic in Colombia was sparked by multiple introductions, but sustained primarily by within-country transmission, suggesting that improved surveillance and mosquito control should be prioritized over border closures (Black and Moncla et al., BMC Infectious Diseases, 2019). Following the start of the SARS-CoV-2 pandemic, Dr. Moncla led a study of 133 acutely infected individuals in Wisconsin to show that novel variants generated during infection are rarely transmitted onward, either within the broader community or among members of the same household (Braun et al., PLOS Pathogens, 2021). These findings suggest that short infection times and narrow transmission bottlenecks limit the selection and propagation of novel mutations, which may slow the evolution of new traits like immune escape.
Finally, in 2020, Dr. Moncla partnered with the Washington State Department of Health to investigate an unusual mumps outbreak in Washington State. By employing a novel synthesis of detailed epidemiologic data, feedback from community health advocates, and new phylogenetic methods, she found that a person’s social network can be the primary risk factor for respiratory virus infection and transmission, even when a vaccine is effective and widely used (Moncla et al., eLife, 2021). These findings highlight that addressing economic and health disparities will remain important, even in a setting with high vaccine availability and use, with clear implications for SARS-CoV-2 mitigation strategies. In her new lab, Dr. Moncla is now expanding on these findings through a CDC contract that aims to investigate how a person’s geographic setting (urban vs. rural), immune history (vaccination and infection histories), and access to health resources, impact SARS-CoV-2 infection and transmission patterns. Quantifying the contribution of these factors to infection risk is important for evaluating vaccination efforts (like where to prioritize clinic sites) and designing new public health policies.