Tamara Salloum, PhD

Pronouns

She/Her/Hers

Rank

Research Fellow

Institution

BWH

BWH-MGH Title

Research Fellow, PhD

Department

Division of Allergy and Clinical Immunology

Authors

T. Salloum1,2, D. F. Dwyer1,2, The Immunological Genome Consortium

Transcriptional profiling unveils the heterogeneity of constitutive and inducible mast cells in inflammation and homeostasis

WMSS 2022

My current research focuses on understanding the transcriptional changes associated with constitutive and inducible mast cells (MCs) in inflammation and homeostasis, characterizing MC heterogeneity across several experimental murine disease models and exploring to what extent changes in candidate genes are reflected in human MC transcriptomes. As a mother of two, I find it particularly challenging to make new connections at work while balancing personal and professional responsibilities and expectations. I believe that this is a great opportunity to connect with women faculty and trainees sharing similar research interests and to become part of a bigger community of women in STEM.

Background

Mast cell (MCs) activation and expansion is a common feature of human diseases driven by type 2 (T2) inflammation, including asthma, food allergy and eosinophilic esophagitis. While discrete MC phenotypes are recognized based on protease expression profiles, the full degree of MCs heterogeneity is poorly understood.

Methods

Here, we use transcriptomics to comprehensively characterize MC heterogeneity in steady state, including skin, heart, palate, tongue, adipose tissue, peritoneal cavity, bone marrow and spleen. To assess MCs phenotype during inflammation, MCs were isolated from Nippostrongylus brasiliensis infected lungs and subcutaneous adenocarcinoma tumors. Basophils were isolated from several tissues for comparison.

Results

We find substantial MC heterogeneity across tissues and disease states. In addition to canonical MC proteases, MCs differentially expressed a range of signaling and activating receptors, and pro-inflammatory mediators. A number of transcripts upregulated within murine adenocarcinomas were similarly observed in human adenocarcinomas, suggesting a shared tumor-associated program across species. Inflammation-expanded MCs were found to retain a BM-associated transcriptional ‘fingerprint’ that included the basophil-associated transcript Mcpt8, which expression was further confirmed using a Mcpt8 reporter strain.

Conclusions

These results underline the extraordinarily transcriptional heterogeneity of MCs exhibiting tissue specific responses, providing new insights into MCs in homeostasis and T2 inflammation.