Differential expression and processing of CABS1 across tissues and fluids and its location-specific functions.

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In 2015, our research group at the University of Alberta discovered that calcium binding protein, spermatid-associated 1 (CABS1) is detected in human saliva. Previously, CABS1 protein had been found in other species and almost exclusively in the testes. Thus, little was known about CABS1 and its biology. Two years later, a subsequent study by our group showed that CABS1 was involved in control of inflammation and is under neurogenic regulation, with one form of CABS1 in human saliva up-regulated by psychological stress, while smaller sized forms were associated with resilience to stress. This duality of CABS1 ignites many intriguing questions regarding its relevance. My long-term objectives are basic science driven, stemming from a desire to unravel how CABS1 is regulated at the cellular level and determine its functions. In the short term, my objectives are to define epithelial sources of CABS1 production and its processing into multiple forms, as well as the effect of CABS1 on neutrophil biology. Aim 1 of this program will identify CABS1 expression in different tissues and body fluids of rat and human origin, Aim 2 will elucidate the signaling pathways that regulate CABS1 production and release, and Aim 3 will characterize the anti-inflammatory roles of CABS1 on the biology of human neutrophils. I am highly qualified to conduct this research on CABS1 based on my extensive research experience on inflammatory pathways of epithelial and immune cells. My current MSc student and I have already made significant contributions in validating our polyclonal antibodies to CABS1 and we are currently establishing best methodologies for this work, including 2-dimensional electrophoresis coupled with mass spectrometry analysis that will help us carry out components of Aims 1 and 2. I have established strong collaborations with professors with expertise in proteomics and neutrophil biology, who can provide support and advice on our experiments. The foundation of this basic research on CABS1 regulation and function will garner insight on how CABS1 contributes to anti-inflammatory processes. My research may reveal other unrecognized roles of CABS1. This program on CABS1 aligns well with the role of NSERC in helping researchers "produce world-firsts in knowledge". Being the first to elucidate the regulation of CABS1, a curious yet emerging protein with promising results, is an exciting prospect. Establishing a Canadian program for CABS1 research is a step towards global excellence in the field of neuro-endocrine pathways that regulate salivary and other epithelial physiology.