Rothenberg CURED Lab
Current Projects

Proteases and Protease Inhibitors in Inflammation

The Rothenberg CURED Lab is pursuing the key role of proteases, both within allergens and those produced endogenously, as regulators of allergic responses. Likewise, deficiency of protease inhibitors, such as serine protease inhibitor Kazal-type (SPINK) as a key check point, is being pursued.

Esophageal Allergy as Protease-mediated Disease

 KLK5 STM graphical summary image.

An imbalance of specific proteins, proteases and protease inhibitors, in cells lining the esophagus may cause inflammation and tissue damage in people with eosinophilic esophagitis (EoE). In people with active EoE, biopsies of esophageal tissues show a near-complete lack of the protease inhibitor SPINK7, which normally damps down inflammation and helps preserve tissue structure. In this study, researchers of the Azouz Lab and Rothenberg CURED Lab found a missing link that further explains how the process works. SPINK7 normally binds with the protease kallikrein 5 (KLK5), keeping it in check. Without enough SPINK7, KLK5 is free to degrade tissues and start signals leading to inflammation. These findings highlight esophageal allergy as a protease-mediated disease, suggesting that disarming of proteases by delivering protease inhibitors has the potential to be therapeutic in allergic disease.

Current Projects

  • Role of protease inhibitors such as SPINK7 and related proteases such as kallikreins (KLKs)

Kallikreins in EoE

Our data, published in Mucosal Immunology, suggest that kallikrein (KLK) expression is dysregulated in the esophagus of patients with active eosinophilic esophagitis (EoE) and in interleukin 13 (IL-13)-treated esophageal epithelial cells. Read more