Function of Zymogen Granule 16B (ZG16B) in Salivary Glands

Oral inflammatory conditions such as Chronic graft versus host disease (cGVHD) and Oral Lichenoid Lesions (OLL) commonly affect oral exocrine tissues including minor salivary glands (MSG) that require incisional tissue biopsy for diagnosis. Saliva, a biofluid with complex composition, is secreted by the acinar cells of salivary glands to help in important oral functions such as lubrication, digestion, and importantly, to elicit anti-inflammatory responses providing the potential to present specific biomarkers that reflect health and disease status. Being able to collect saliva through patient-friendly, non-invasive methods is an important advantage of utilizing this biofluid for oral and systemic disease diagnostics. Recent shotgun proteomic screening work from our laboratory identified a significant reduction in protein content of zymogen granule 16B (ZG16B), a jacalin-related lectin protein, at onset of salivary gland cGVHD compared to healthy donors. Lectin proteins have a carbohydrate domain and adjacent positively charged binding pocket that can facilitate cell-to-cell interactions and immunomodulation contributing to important oral cavity tissue homeostasis. Therefore, we hypothesize that ZG16B is required to coordinate the localization and release of acinar cell secretions. Changes in ZG16B levels in states of altered oral tissue homeostasis can signal salivary gland damage. Aims 1 and 2 focuses on determining the distinct binding partners of ZG16B in human salivary gland (HSG) cells and conditioned media as well as its functional consequence. This will be fulfilled by endogenous co-immunoprecipitation, mass spectrometry, loss-of-function and gain-of-function experiments followed by entire RNA sequencing analysis. Aim 3 will quantify the changes in concentration of salivary ZG16B using sex-matched samples from healthy individuals and saliva from patients with various oral inflammatory conditions damaging salivary gland (oral cGVHD and OLL). This will be fulfilled using ELISA-based salivary ZG16B screening validated with immunohistochemistry staining using tissue slides. The completion of this project will provide rigorous training in biochemistry, salivary gland biology and saliva-based diagnostics enhanced in an interinstitutional research agreement (NIH Graduate Program Partnership) between Indiana University School of Dentistry (IUSD) and National Institute of Dental and Craniofacial Research (NIDCR). This collaboration incorporates excellent mentorship in clinical and translational research to prepare the applicant for a career as a dentist-scientist. Project Number: 1F30DE034308-01A1 | Fiscal Year: 2025 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: Drashty Mody | Institution: INDIANA UNIVERSITY INDIANAPOLIS, INDIANAPOLIS, IN | Award Amount: $55,338 | Activity Code: F30 | Study Section: Special Emphasis Panel[ZDE1 JC (08)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11244471