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Investigating antigen specific adaptive immune cells to better design vaccines and therapeutics
The Seattle Hub for Synthetic Biology is a collaboration between Allen Institute, Chan Zuckerberg Initiative and the University of Washington.
The Pepper Lab
In the Pepper Lab, researchers study how cells of the adaptive immune system, called CD4+ T cells and B cells, form immunological memory by visualizing their differentiation, retention, and function in both mice and humans. They accomplish this by using novel tetramer-based enrichment strategies to study small populations of antigen specific CD4+ T and B cells in both complex infectious diseases, such as malaria as well as during allergic asthma using a house dust mite model. They additionally use transgenic mice with various genetic ablations to interrogate the underlying molecular mechanisms involved in memory cell development and function.
Lead Investigator: Dr. Marion Pepper
Dr. Marion Pepper earned her Ph.D. in Immunology in 2006 from the University of Pennsylvania School of Medicine. Her work there focused on the development of the CD4+ T cell response to the eukaryotic parasite, Toxoplasma gondii in the laboratory of Dr. Christopher A. Hunter. She continued to study the adaptive immune response as a postdoctoral scholar, specifically focusing on memory lymphocyte differentiation and function in Dr. Marc K. Jenkins’ lab at the University of Minnesota.
In 2011, she joined the faculty of the Department of Immunology at the University of Washington in Seattle as an Assistant Professor. The overarching goals of her laboratory are to understand how to regulate immune cell differentiation such that memory responses against infections can be optimized, while those against allergy can be suppressed. Her studies have revealed key differentiation programs and functions of both memory CD4+ T cells and B cells in response to pathogens and allergens. In 2017, she was awarded the Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Diseases Award and was promoted to Associate Professor. In 2021, she was awarded the International Cytokine and Interferon Society ICIS-Luminex John R. Kettman Award for Excellence in Interferon & Cytokine Research. In 2022, she was named Chair of the University of Washington School of Medicine Department of Immunology, and in 2023, she was promoted to Professor.
The Pepper Lab studies the adaptive immune system with the goal of generating protective T and B cells in response to a variety of infectious diseases including those caused by parasites, viruses and bacteria. Research in the Pepper Lab during the COVID pandemic found that “certain ‘memory’ cells that were produced following infection with the coronavirus [were functional and could] persist for at least three months in the body,” (New York Times, 2021).
The Pepper lab also is working on understanding how to dampen immune memory responses in allergic diseases. Research on dust mite allergy in the Pepper Lab has shown that “lung-resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4(+) T cells,” (Immunity, 2016). Her lab is now focused on understanding the persistence and function of these cells in an effort to create novel therapeutic targets for allergic disease.
The SeaHub project draws on the Pepper Lab’s expertise in immune memory and creating novel tools and techniques to enhance scientists’ understanding of the cells that determine health or disease. They will focus on developing immune cells that can record signals sequentially and longitudinally. This will allow researchers to better understand how T cells that are pathological or optimally protective are generated such that they can be eventually targeted by novel therapeutics.
Dr. Pepper also leads the SeaBridge Fellowship Program, whose goal is to train future scientists and boost commercialization of technology by expanding the application of technologies from the Seattle Hub for Synthetic Biology. SeaBridge Fellows apply SeaHub science to their own postdoc research.
