Silencing Mast Cells
A novel platform enables new insights into mast cell function in allergic disease
Technology Overview
Dr. Adrian M. Piliponsky
Mast cells are key players in the immune system, but their dysregulation or overactivation can result in allergic reactions and other allergic diseases, including asthma, chronic urticaria (hives), mastocytosis and mast cell activation syndrome (MCAS). These cells contain granules that are rich in histamine and other pro-inflammatory molecules that they release upon mast cell activation.
Mast cells contain many proteins on their surfaces that interact with other cells and molecules and regulate mast cell functions, either by activating or suppressing them. One such class of mast cell surface proteins are sialic acid-binding immunoglobulin-type lectins (also known as “Siglecs”). Pediatric immunologist Adrian M. Piliponsky, PhD, has found that one of these Siglecs, Siglec-9, inhibits mast cell activation when it is bound to its ligands, implying that this protein could be a potential drug target to reduce erroneous mast cell activation that is present in diseases such as allergy and asthma.
In an animal model of asthma, Dr. Piliponsky found that Siglec-9 is important to reduce bronchial constriction when the animals are exposed to dust mites, which are an asthma trigger. Additionally, in collaboration with pediatric pulmonologist Jason Debley, MD, at Seattle Children’s Research Institute, the Piliponsky Lab has developed a unique cell model to study human mast cells in vitro. This model is a co-culture of mast cells and airway epithelial cells (AECs) and is the first system of its kind to study these two cell types together.
Additionally, Dr. Piliponsky is studying the role of Siglec-9 in innate immunity in two areas: pediatric asthma and maternal infection by group B streptococcus (GBS), which is the main pathogen associated with preterm birth. In collaboration with pediatric infectious disease researcher Lakshmi Rajagopal, PhD, at Seattle Children’s Research Institute, Dr. Piliponsky has demonstrated in in vitro studies that Siglec ligands displayed by the vaginal epithelium can stop immune cells from killing GBS.
Dr. Piliponsky is interested in industry partnerships to further explore therapeutics based on Siglec activation for allergy, asthma and other mast-cell related diseases, including designing or identifying small molecules that bind Siglec proteins, and performing in vitro tests to explore their potential as therapeutics. His novel platform for studying mast cells and epithelial cells in co-culture can be utilized in collaborative research.
Stage of Development
- Preclinical in vitro
- Preclinical ex vivo
- Preclinical in vivo
Partnering Opportunities
- Collaborative research and development
- Sponsored research agreement
- Consultation agreement
- Tissue sample access
- Cell line access
- Animal model access
Publications
- Miralda I, Samanas NB, Seo AJ … Piliponsky AM. Siglec-9 is an inhibitory receptor on human mast cells in vitro. J Allergy Clin Immunol. 2023;152(3):711-724.e14.
- Murphy RC, Chow YH, Lai Y … Piliponsky AM, Hallstrand TS. Identification of mast cell progenitor cells in the airways of individuals with allergic asthma. Allergy. 2023;78(2):547-549.
- Piliponsky AM, Sharma K, Quach P … Rajagopal L. Mast cell-derived factor XIIIA contributes to sexual dimorphic defense against group B streptococcal infections. J Clin Invest. 2022;132(20):e157999
- Gendrin C, Shubin NJ, Boldenow E … Rajagopal L, Piliponsky AM. Mast cell chymase decreases the severity of group B Streptococcus infections. J Allergy Clin Immunol. 2018;142(1):120-129.e6.
- Gendrin C, Vornhagen J, Ngo L … Piliponsky AM, Rajagopal L. Mast cell degranulation by a hemolytic lipid toxin decreases GBS colonization and infection. Sci Adv. 2015;1(6):e1400225
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