Mast Cell Biology and Therapeutics
Exploring novel therapeutics targeting mast cells in allergic disease
Technology Overview
Dr. Adrian M. Piliponsky
Mast cells are a type of immune cell that are key drivers of allergies and asthma and play important roles in many other diseases, including several autoimmune diseases. Pediatric immunologist Adrian M. Piliponsky, PhD, is an expert in mast cell biology. His research has uncovered previously unknown roles for receptors and transporters on the mast cell surface, characterizing how these molecules regulate mast cell function.
When mast cells are activated, they release granules that contain histamine and other pro-inflammatory molecules. This activity is important in pathogen defense and other normal immune reactions, but the immune response can go awry and lead to overactive, acute reactions and chronic inflammation, such as anaphylaxis and allergies. Although clinical researchers historically have shied away from treatments that delete mast cells entirely because of concerns about negative side effects, some studies have found that deleting mast cells can lead to improvements in asthma and urticaria (also known as hives).
In collaboration with protein engineer Jason Price, PhD, at Seattle Children’s Research Institute, Dr. Piliponsky is developing immunotherapy approaches to target other proteins, called Siglec proteins, on the mast cell surface in the hopes of eliminating mast cells. The research team currently is exploring this approach for mast cell leukemia, which is a rare and aggressive subtype of acute myeloid leukemia (AML), and they hope to broaden the research to other diseases in the future.
Additionally, the Piliponsky Lab is exploring new aspects of mast cell biology, with the hopes of discovering even more potential drug targets for mast cell-related diseases. Together with pediatric immunologist Richard James, PhD, at Seattle Children’s Research Institute, Dr. Piliponsky is studying a class of proteins known as solute carrier proteins (SLCs) that control the efflux of several different kinds of molecules across cell membranes. These proteins are understudied in terms of drug discovery.
The researchers have found that one of these SLCs, CD98hc, is important for mast cell function — when it is deleted, mast cells have reduced ability to store and release histamine. The research team currently is conducting a high-throughput screen to identify other SLCs that influence mast cell function.
Dr. Piliponsky is an expert in mast cells, lung function and rational drug design/drug development. He also has deep experience in cell cultures (e.g., ex vivo human co-culture models of mast cells with airway epithelial cells from healthy and asthmatic pediatric donors) and animal models. The Piliponsky Lab has expertise in gene editing of human primary mast cells and airway epithelial cells, as well as mass spectrometry analysis of primary mast cells. He is interested in industry collaborations to further develop his novel mast cell-targeting therapeutics and explore additional drug targets on mast cells.
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
- 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.
- Saha SS, Samanas NB, Miralda I … Piliponsky AM. Mast cell surfaceome characterization reveals CD98 heavy chain is critical for optimal cell function. J Allergy Clin Immunol. 2022;149(2):685-697.
- Piliponsky AM, Acharya M, Shubin NJ. Mast cells in viral, bacterial, and fungal infection immunity. Int J Mol Sci. 2019;20(12):2851.
- Shubin NJ, Glukhova VA, Clauson M … Piliponsky AM. Proteome analysis of mast cell releasates reveals a role for chymase in the regulation of coagulation factor XIIIA levels via proteolytic degradation. J Allergy Clin Immunol. 2017;139(1):323-334.
- Piliponsky AM, Romani L. The contribution of mast cells to bacterial and fungal infection immunity. Immunol Rev. 2018;282(1):188-197.
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