Presnell & Altman Laboratory

Amongst other projects, our lab works within 3 groups, funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health: the Inner-City Asthma Consortium (ICAC), the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) and the Immune Tolerance Network (ITN). In studies with these collaborators, we use network analysis techniques such as cell-deconvolution and modular analysis to reduce the dimensionality of complex data, while simultaneously focusing on the salient elements of the immune response (Chaussabel, Baldwin 2014; Obermoster et al 2013; Li et al 2014). Collaborations like these help understand complex diseases while laying the groundwork for the discovery of new treatment approaches.

Inner-City Asthma Consortium

The Inner-City Asthma Consortium (ICAC) is a NIAID sponsored multi-center initiative studying causes of the urban asthma epidemic and developing treatments to improve control of asthma in this population and for children in general. The Presnell-Altman lab applies transcriptomic, multi-omic and computational approaches to investigate mechanisms of disease within the ICAC clinical and translational studies. Since 2014, we have been investigating mechanisms of asthma inception within the Urban Environment and Childhood Asthma (URECA) birth cohort of more than 500 children at high risk for asthma. In this study, ICAC investigators are able to closely follow the natural history of asthma development and better understand who develops asthma, why, and what subtypes of asthma exist in the population (Altman et al 2018).

Figure 1: Natural Killer Cell gene network from atopic URECA subjects

In two paired studies, Mechanisms Underlying Asthma Exacerbations Prevented & Persistent with Immune-Based Therapy: A Systems Approach (MUPPITS), part 1 and part 2, we are defining detailed inflammatory mechanisms of asthma exacerbations in school-aged children (Altman et al 2019). In MUPPITS-1 we defined the pathways in both respiratory virus induced and non-viral exacerbations, as well as genetic and environmental contributors to exacerbations. In MUPPITS-2 we are investigating the efficacy and mechanisms of exacerbation prevention with an anti-IL5 monoclonal antibody targeting eosinophilic inflammation.

Figure 2: Eosinophil activation in asthma exacerbations in the MUPPITS-1 study

Immunophenotyping Assessment in a COVID-19 Cohort

As part of the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC), we are studying approximately 1,000 COVID-19 patient responses to SARS-CoV-2 infection longitudinally in order to identify immunophenotypic, virologic and genomic features of COVID-19-related susceptibility and/or disease progression and severity. Specifically in phase I of the study, we are detailing the airway transcriptome response in the context of COVID-19 to better understand the immunologic impact of the virus at the primary site of infection. In phase II of the study, we will integrate our transcriptome data with detailed clinical and molecular data across the cohort to understand a broader view of the host response to virus. The goal of IMPACC is to generate hypotheses for effective host-directed therapeutics and to optimize timing for administration of these host-response directed interventions.

Immune Tolerance Network

The Immune Tolerance Network (ITN) is a collaborative network for clinical research, funded by NIAID. Its mission is to accelerate the clinical development of immune tolerance therapies. The ITN’s allergy and asthma portfolio has focused on modifying validated desensitization protocols to induce durable tolerance. We are studying transcriptome changes in the airway that are responsible for allergic sensitization and the immunologic mechanisms by which immune tolerance to allergens is achieved.