The development of accurate models that permit prediction of biological responses upon perturbation has the potential to increase our mechanistic understanding of pathophysiology and contribute to the development of improved therapeutics. The human immune system provides an excellent context for developing such systems biology approaches: many immune cells and molecular components are readily accessible from blood, permitting collection of samples from individuals across multiple time-points, followed by in depth data generation and analyses. Furthermore, there is an increasing understanding that the immune system and inflammation contribute to the pathogenesis of multiple disorders. These include not only those classically considered to involve the immune system such as autoimmune and infectious diseases, but also cancer, cardiac disease, diabetes, obesity, neurodegeneration, and other chronic illnesses affecting a large segment of the population (Germain and Schwartzberg, Nat Immunol. 2011). Thus, a more comprehensive and quantitative understanding of how immune responses are orchestrated, together with identification of predictive molecular and cellular parameters of effective vs. damaging responses, could have major implications for the prevention and treatment of diverse diseases. To this end, I helped coordinate one of the initial studies from the NIH Center for Human Immunology designed to help build a data base of normal human variation (the human immunome) and understand how variation in immune states contributes to immune reponses and disease (Tsang, Schwartzberg et al, Cell 2014; DIckler, H. et al, Ann New York Acad Sci, 2013). We are now conducting analyses from a follow-up study comparing responses to both an unadjuvented and an adjuvented vaccine against Influenza H5N1. To complement our work, we have added new assays characterizing follicular T helper cells, a key T cell population that helps B cells make long-term antibody responses. We are using these approaches to look at responses to immunization in greater depth and to optimize technical and scientific approaches to better understand what generates productive responses to vaccines. We are completing the first set of bioinformatic analyses of these data and preparing a paper on this topic.
| Olnes, Matthew J; Kotliarov, Yuri; Biancotto, Angélique et al. (2016) Effects of Systemically Administered Hydrocortisone on the Human Immunome. Sci Rep 6:23002 |
| Tsang, John S; Schwartzberg, Pamela L; Kotliarov, Yuri et al. (2014) Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell 157:499-513 |
| Dickler, Howard B; McCoy, J Philip; Nussenblatt, Robert et al. (2013) The National Institutes of Health Center for Human Immunology, Autoimmunity, and Inflammation: history and progress. Ann N Y Acad Sci 1285:133-47 |
