We make new computational immunology methods, and collaborate with experimental biologists to make broad insights in adaptive immunity.
New computational methods development
The core focus of the Hoehn lab is to develop new computational methods that use single B cell sequencing to understand adaptive immune responses in humans and model systems. These are almost always inspired by techniques from molecular evolutionary biology, such as phylogenetics. Our grand vision is to be able to study B cells responding to immune stimuli in the same way that virologists study viruses evolving during epidemics. Our past work solved the sub-problems leading to this vision, including building B cell phylogenetic trees, measuring B cell evolution over time, and detecting B cell migration between tissues. These techniques have been implemented in our open-source packages IgPhyML and Dowser. Our current work focuses on creating a phylogenetic framework for inferring all of these processes from sequencing data.
Infection and vaccination
B cells produce antibodies, which neutralize invading viruses and other pathogens. During infection, B cells mutate their antibody-producing genes to make better antibodies. Vaccines usually attempt to trigger this process to produce long-lived memory B cells. A major focus of our collaborative work is in using computational immunology to understand infections and make better vaccines. This ranges from influenza vaccination to Lyme disease. We have also worked extensively to understand immune reactions related to COVID-19, including distinguishing mild and severe cases, understanding COVID-19 in the upper-respiratory tract, and associated autoimmune pathologies.
Autoimmune disease
While antibodies are supposed to bind to pathogens, they sometimes attack our own tissues, causing types of autoimmune disease. Much of our collaborative work in this area focuses on myasthenia gravis, in which B cells produce antibodies that bind to the neuromuscular junction, causing loss of skeletal muscle function. Our work has helped understand where pathogenic B cells arise from and why relapses occur after B cell depletion therapy. We also have projects with collaborators aiming to understand unique B cell populations that drive the development of lupus.
Food allergies
B cells also cause food allergies by producing IgE antibodies, which can bind to food particles and cause allergic symptoms. In an ongoing collaboration, our goal is to understand how these pathogenic IgE-producing B cells arise, including how they are maintained over time.
Cancer
B cells have dual roles in cancer. Recent work has shown that B cells can fight tumors, and could potentially be used as a form of immunotherapy. A major focus of our current work is in understanding the mechanisms of how B cells respond to tumors and immunotherapies. On the other hand, B cells can themselves become cancerous and develop into lymphomas, and we have worked with collaborators to show how subtle changes in B cell evolutionary dynamics can drive lymphoma development.