The calcium sensor dream contributes to pollutant induced pancreatic stress

The National Institute of Environmental Health Sciences awarded the California State University Long Beach Research Foundation $138,202 on August 1, 2026, under the Environmental Health program (CFDA 93.113) to investigate how calcium signaling disruption induced by environmental pollutants alters pancreatic cell function and glucose homeostasis.

The project examines the role of the calcium-sensitive protein DREAM (Downstream Regulatory Element Antagonistic Modulator) in pancreatic health outcomes following exposure to polychlorinated biphenyls, bisphenol A, and tetrabromobisphenol A. The research uses zebrafish models—both wildtype and DREAM knockout strains—to detail the impact of calcium signaling disruption in pancreatic alpha and beta cells and connect cellular responses to organismal physiology. The Foundation's prior work in this area demonstrated that calcium signaling disruption exposure alters DREAM-regulated transcription in neuroendocrine cells and that pancreatic tissue displays greater toxicity markers than brain tissue in exposed organisms; many toxicity signs are reduced in DREAM knockout models. Current work will build on RNA sequencing data suggesting altered glucose homeostasis, intracellular calcium regulation, and cell cycle markers in pancreatic tissue.

Performance occurs in Long Beach, California, with a period of performance from August 1, 2026, through July 31, 2030. The assistance type is a Project Grant.

Abstract

Pollutants such as polychlorinated biphenyls, bisphenol a, and tetrabromobisphenol a are risk factors for the development of pancreatic diseases. These pollutants all induce CA2+ signaling disruption (CSD) but how this may alter pancreatic health is unknown. Notably, CA2+ plays a pivotal role in endocrine pancreas function including glucose stimulated insulin secretion and other CA2+ mediated signaling events like transcription. For example, the CA2+-sensitive protein dream (downstream regulatory element antagonistic modulator) regulates transcription of pre-proinsulin and prodynorphin in β-cells. Additionally, dream is found in glucagon secreting α-cells but IT role has not been evaluated. Thus, our main hypothesis is that CSD exposure will alter islet cell CA2+ homeostasis causing altered CA2+ regulated process like transcription and secretion related to the CA2+ sensor dream. Importantly, our lab has recently confirmed that CSD exposuse can alter dream regulated transcription in neuroendocrine cells and started to assess tissue specific impacts in CSD exposed zebrafish models. Our rnasequencing data in adults suggests that the pancreas displays more signs of toxicity, then the brains, of CSD exposed wildtype (WT) and that many of these signs of toxicity are reduced in CSD exposed dreamb KO (KO). Additionally, pancreatic tissue from dreamb KO zebrafish, compared to WT, display transcriptional markers of altered glucose homeostasis, intracellular CA2+ regulation, and cell cycle and prolifieration.together these findings support CSD impacts on the pancreas and that dream may contribute to CSD organismal pancreatic disease states. The goal of the current proposal is to detail the impacts of CSD in exposed pancreatic α- and β-cells and connect these cellular challenges with changes in organismal physiology in adult and larval WT and dreamb KO zebrafish. Specific aim 1 will confirm that known CSD pollutants alter pancreatic α- and β-cell CA2+ homeostasis using high-speed CA2+ imaging, connect altered CA2+ homeostasis with altered dream regulated transcription and protein secretion in exposed cells with or without dream sirna knockdown, and measure cell metabolic stress in the presence and absence of known CSD pollutants. Pancreatic diseases like diabetes are risk factors for other comlications like cardiac and skeletal muscle myopathies. Thus, specific aim 2 will assess downstream organismal impacts in adult and larval zebrafish . In adult, we will investigate blood glucose and glucagon together with tissue glycogen levels in adult WT and KO exposed to CSD chemicals. We will also investigate the appearance of other physiological complications related to altered pancreatic health by assessing glucose homeostasis, heart rate, and swimming activity in CSD exposed WT and KO larvae. This will be the first study to document CSD in pancreatic cells and to detail the role of dream in the α- and β- endocrine cells in correlation with organismal biomarkers related to pancreas health. Such work will further our understanding of how common environmental risk factors, namely CSD pollutants, contribute to pancreatic disorders like diabetes, pancreatitis, and cancer.