The human immune monitoring core (HIMC) at the Icahn School of Medicine at Mount Sinai (ISMMS) is a novel research center spearheaded by Dr. Merad and colleagues in 2011 and funded by the Dean of ISMMS to promote the development of novel immune profiling tools to help identify novel biomarkers of diagnosis, prognosis, and response to therapy. One of the main challenges to studies of the immune system has been the limited availability of human samples reducing our ability to perform in-depth comprehensive analysis of immune functions in patients. The goal of this application is to develop novel immune profiling tools and functional assays to identify novel targets and novel biomarker of diseases and response to therapy in two clinical areas: food allergy and IBD. The initial focus on these two disease areas reflects the extraordinary ISMMS clinical recruitment of allergic and IBD patients, yet any technological development obtained in this grant will be applied to other inflammatory disease such as atherosclerosis, and skin inflammatory disease including psoriasis and atopic dermatitis for which ISMMS is also a referral center. Food allergy is a common disease of childhood for which there are no treatment or prevention strategies. The Pediatric Allergy and Immunology division at ISMMS has built one of the most active clinical research programs in food allergy in the country. Mechanistic insights have lagged behind clinical gains due to the difficulty of profiling allergen-specific cells, particularly given the challenge of small blood volumes available from pediatric patients. Thus one of the goals of this proposal is to develop novel immune and genomics tools to identify and profile allergen-specific T cells at the single-cell level. The ISMMS Inflammatory Bowel Disease (IBD) Center is unique in its close, integrated collaborations between world-leaders in clinical, genetic, microbiome and immunology-based IBD research. While efforts to explore immune regulators causative of disease has focused on exploiting GWAS data and exploring systemic dysregulation, little effort has been devoted to comprehend the nature of the immune dysregulation that occurs at the tissue site mainly due to limited availability of gastrointestinal tissue.
Thus Aim 2 of this projet proposes to leverage the extraordinary tissue samples obtained by the ISMMS IBD Center to develop novel immunological assays to profile immune cell compartments that infiltrate and contribute to IBD lesions in early diagnosed patients and at different time after initiation of immunodulatory agents.

Public Health Relevance

The goal of this application is to develop novel immune profiling tools to assess the dysregulation of allergen- specific T cells in food allergic childrenas well as dissect the nature and functional state of the immune cell compartment that infiltrate and contribute to inflammatory gut tissue lesions in IBD patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
1U24AI118644-01
Application #
8935201
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Davidson, Wendy F
Project Start
2015-06-30
Project End
2020-05-31
Budget Start
2015-06-30
Budget End
2016-05-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Amir, El-Ad David; Guo, Xinzheng V; Mayovska, Oksana et al. (2018) Average Overlap Frequency: A simple metric to evaluate staining quality and community identification in high dimensional mass cytometry experiments. J Immunol Methods 453:20-29
Chiang, David; Chen, Xintong; Jones, Stacie M et al. (2018) Single-cell profiling of peanut-responsive T cells in patients with peanut allergy reveals heterogeneous effector TH2 subsets. J Allergy Clin Immunol 141:2107-2120
Hectors, Stefanie J; Wagner, Mathilde; Bane, Octavia et al. (2017) Quantification of hepatocellular carcinoma heterogeneity with multiparametric magnetic resonance imaging. Sci Rep 7:2452
Goswami, Ritobrata; Blazquez, Ana Belen; Kosoy, Roman et al. (2017) Systemic innate immune activation in food protein-induced enterocolitis syndrome. J Allergy Clin Immunol 139:1885-1896.e9
Stern, Alan D; Rahman, Adeeb H; Birtwistle, Marc R (2017) Cell size assays for mass cytometry. Cytometry A 91:14-24
Agashe, Charuta; Chiang, David; Grishin, Alexander et al. (2017) Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells. J Immunol Methods 449:23-27
Lavin, Yonit; Kobayashi, Soma; Leader, Andrew et al. (2017) Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses. Cell 169:750-765.e17
Rahman, Adeeb H; Tordesillas, Leticia; Berin, M Cecilia (2016) Heparin reduces nonspecific eosinophil staining artifacts in mass cytometry experiments. Cytometry A 89:601-7
Tordesillas, Leticia; Rahman, Adeeb H; Hartmann, Boris M et al. (2016) Mass cytometry profiling the response of basophils and the complete peripheral blood compartment to peanut. J Allergy Clin Immunol 138:1741-1744.e9