Angela Rasmussen

During her tenure at University of Washington, she studied the response of mice to ebolavirus infection. The traditional mouse model, which is derived from a uniform genetic background, dies after being infected with the virus before the classical symptoms of the disease show up, making it difficult to study the pathogenesis of the virus.[3] Instead, Rasmussen and her team took advantage of a genetically diverse collection of mice, known as the Collaborative Cross; when infecting this collection of mice with ebolavirus, they observed a wide range of disease outcomes, ranging from complete resistance to the virus to severe hemorrhagic fever.[3] They concluded that the genetic background of the mice therefore plays a role in their susceptibility to the virus.[4] By understanding which genes in mice affect the course of infection, they can better determine which genes make humans more susceptible to the disease—and why some humans die, while others survive.[5][6]

Rasmussen has continued work on understanding genetic susceptibility to Ebola, bringing this genetically diverse system of mice with her to her research group at Columbia University. There, she identified a gene expression signature that may predict the severity of Ebola infection.[7] Rasmussen and collaborators have also used human cell lines to investigate the course of infection. Upon infection, ebolavirus first targets macrophages, or white blood cells that engulf and clear away pathogens, which in turn release inflammatory cytokines that recruit more immune cells to the site of the infection to kill off infected tissue. If cytokine release goes unchecked it can lead to a profound inflammatory response—known as a cytokine storm—that can kill off healthy tissue, as is the case with an ebolavirus infection.[8] She and collaborators found that inhibiting the inflammatory response of virus-infected macrophages could be a potential therapeutic target, preventing a cytokine storm from occurring.[9]

Rasmussen's work investigating the heterogeneity in Ebola infections has translated into developing hypotheses around why some COVID-19 cases are worse than others.[10] Possible explanations include a dysfunctional immune system in the elderly and those with pre-existing conditions that more readily results in a cytokine storm, causing inflammation in the lungs that ripples out to the rest of the body, as well as genetic and environmental risk factors.

She has also been on the frontlines of communication around the novel coronavirus and COVID-19, applying her expertise in correspondence with the popular press to interpret preliminary results around how long immunity to the virus may last, how effective potential drugs may be in treating the disease, and whether biological sex plays a role in the severity of the disease.[11][12][13] Given the breakneck pace at which preliminary research results have been released—for example, through preprints—she has urged caution in reporting research findings too quickly and without the proper caveats to ensure the public is not misinformed.[14]

• "Transcriptional Correlates of Tolerance and Lethality in Mice Predict Ebola Virus Disease Patient Outcomes." Cell Reports 30(6): 1702–1713. February 11, 2020. DOI: 10.1016/j.celrep.2020.01.026
• "Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance." Science 346(6212): 987–91. November 21, 2014. DOI: 10.1126/science.1259595