Dr. Gunn completed her PhD at the University of North Carolina in Chapel Hill in the laboratory of Mark Heise, PhD. Her thesis work focused on identifying both viral and host factors in the disease pathogenesis of the alphavirus, Ross River Virus, and demonstrated a role for viral glycosylation in disease pathogenesis. Dr. Gunn went on to do her post-doctoral fellowship at the Ragon Institute of MGH, MIT, and Harvard in Cambridge, MA in the laboratory of Galit Alter PhD, where she studied how antibodies use innate immune cells to provide protection against Ebola virus infection.
I joined the faculty at the Paul G. Allen School of Global Animal Health as an assistant professor in February 2020.
I am originally from northern Australia but have lived most my life in the US. Having survived a malaria infection as a small child while traveling in Papua New Guinea, I’ve always been motivated to help develop vaccines and therapeutics against infectious diseases. I began my research career as a high school student in New York City dissecting mosquito salivary glands to isolate malaria parasites at New York University. It was fascinating for me as a young student to be in a lab, so I continued lab work as an undergraduate at Washington University in St. Louis, working with Dr. Roy Curtiss III on developing recombinant attenuated Salmonella vaccines. I moved on to studying viruses for my PhD and worked on understanding how Ross River Virus, a mosquito-borne alphavirus present in Australia, causes disease. We found that much of the arthritis and muscle damage associated with infection was actually caused by the innate immune system, highlighting the critical need for the immune system to balance protection and pathology.
Figuring that I needed to learn a lot more about the immune system, I began studying antibodies with Dr. Galit Alter as a post-doctoral fellow. I studied how antibodies interact with and activate innate immune cells to protect against viral infection and became really interested in the breadth of antibody functions and the ability of antibodies to orchestrate antiviral immunity in multiple ways.
Outside of lab, I like to spend my time birding with my husband, which brings us to beautiful and unexpected places. When not out exploring, I enjoy being at home testing recipes and spoiling my cat Squiggles.
2000-2004 BA; Washington University in St. Louis, St. Louis MO USA
2007-2013 PhD; University of North Carolina at Chapel Hill, Chapel Hill NC USA
2013-2019 Post-doctoral fellow; Ragon Institute of MGH, MIT, and Harvard University, Cambridge MA USA
The emergence and reemergence of zoonotic viral diseases into the human population accounts for over half of infectious diseases worldwide. Diseases such as Ebola virus disease (EVD), Middle East Respiratory Syndrome (MERS), Lassa Fever, and the recent coronavirus outbreak in China have demonstrated the explosive nature of zoonotic viruses and highlight the need for vaccines and therapeutics to prevent and treat infection. Antibodies have been shown to mediate protection against the highly pathogenic Ebola virus for both monoclonal antibody therapeutics and vaccination, and emerging data from other zoonotic viruses suggest that passive transfer of monoclonal antibodies can provide protection. Thus, antibody-based therapeutics may be critical in the treatment of people infected with these viruses.
Antibodies are the effector molecules of the humoral immune system. While antibody production against a pathogen is often used as a marker of protective immunity, our understanding of how antibodies contribute to protection against a variety of pathogens is constantly expanding. Antibodies recognize pathogens with the Fab domain, and Fab-mediated neutralizing activity is often regarded as the primary function of antibodies. Yet, antibodies engage many different innate immune cells, including NK cells, macrophage, monocytes, neutrophils, and dendritic cells to elicit effector functions, such as phagocytosis and cellular cytotoxicity, through the antibody Fc domain that can contribute to protection and resolution of infection. We most recently showed a critical role for the induction of these effector functions in the context of protective monoclonal antibodies against the highly pathogenic Ebola virus.
My work in the Ebola virus field began in 2014, right in the middle of the 2013-2016 epidemic of Ebola virus disease (EVD) in West Africa. With no approved vaccines or therapeutics, the epidemic spurred the rapid evaluation of promising candidates, including the antibody cocktail ZMapp and the VSV-ZEBOV vaccine, which relied on antibodies for efficacy. While neutralizing activity is undoubtedly a key component of protection, neutralization alone could not fully explain the protective efficacy of either the vaccine or ZMapp. During my post-doc at the Ragon Institute, I began evaluating non-neutralizing functions of Ebola-specific antibodies to determine if protective antibodies leverage the innate immune system to help control and clear virus.
Using a high-throughput comprehensive “Systems Serology” antibody profiling platform, we were able to identify the specific antibody features that contribute to monoclonal antibody-mediated protection against Ebola virus. Working with the Viral Hemorrhagic Immunotherapeutics Consortium, we analyzed a large panel of Ebola virus-specific monoclonal antibodies to identify features that tracked with in vivo protection, and found that recruitment of innate immune effector functions is associated with antibody-mediated protection not only for antibodies without neutralizing activity but also for antibodies with strong neutralizing activity. These results have helped in the design of new monoclonal therapeutics and have changed how the filovirus field views mechanisms of antibody-mediated protection against these highly pathogenic viruses.
Following on these findings, we have analyzed the antibody response in human survivors of the 2013-2016 EVD epidemic in West Africa and found that their humoral responses are characterized by highly functional long-lived antibodies. We are now leveraging antibody-engineering tools to generate monoclonal antibodies that can induce specific effector functions to understand how different functions control viral infection in order to aid in the design of highly effective therapeutic antibodies.
My research lab is interested in understanding how antibodies use different innate immune cells to provide protection from viral infection, and whether specific antibody functions modulate outcome of disease in both human and animal hosts. Understanding how the antibody Fc-domain leverages different innate immune cells may lead to the development highly effective antibody therapeutics as well as uncover novel mechanisms by which antibodies can limit viral dissemination throughout the body, prevent transmission, and lead to long-term protective immunity.
To do this, we use a series of high-throughput assays using both primary innate immune cells and cell lines to evaluate the ability of antibodies to induce different effector functions. We use recombinant monoclonal antibodies and serum samples from humans and animals to dissect the role of antibodies in protection against viral infection and use antibody-engineering tools to help generate next-generation therapeutic antibodies against emerging zoonotic viruses. We work with a fantastic group of collaborators from many different fields, and we firmly believe that an interdisciplinary approach is needed to tackle these pathogens.