Systems immunology to understand host-pathogen interactions
Tuberculosis: TB is a major cause of global morbidity and mortality, killing up to 1.5 million people every year. Despite tremendous progress in our understanding of TB, infections are increasing, multidrug resistant bacterial strains are on the rise, and impoverished people with little access to long, expensive treatments continue to bear the brunt of disease. The only existing vaccine against TB was developed more than 90 years ago and is largely ineffective in certain populations and against pulmonary TB. The largest barrier to development of an effective TB vaccine is our failure to understand the fundamental characteristics of a protective immune response.
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Immune dynamics: The goal of our lab is to understand the cellular and molecular regulators of immunity in barrier tissues. We study the dynamics of the host response to infection - how cells respond to changes in their environment, including soluble mediators, cellular interactions, and changes in antigen, nutrient and oxygen availability. These cues are integrated to promote the generation of both transient and stable fates. A better understanding of this process is essential in order to improve vaccine design, particularly as different strategies may be needed for prophylactic, post-exposure or therapeutic vaccines.
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Systems Immunology: There has been a recent explosion of single cell techniques for investigating transcriptional responses at an unbiased single cell level as well as multiplexed microscopy approaches to identify and quantify cellular spatial relationships. In addition, we have established a novel approach to address the differentiation and plasticity of immune cells and their progeny ex vivo, using time-lapse microscopy. By applying these single cell technologies we aim to advance our understanding of anti-tuberculosis immunity, using a macro-to-micro approach: we start from the whole organ, examine specific immune cell subsets, and then proceed to molecular determinants of individual cell fates and function.
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