We study the cell biology of endocrine and neuroendocrine cells, focusing on the mechanisms of biosynthesis and intracellular trafficking of peptide hormones and neuropeptides and their processing enzymes, the regulation of dense-core secretory granule biogenesis, and the enzymatic and non-enzymatic roles of the prohormone processing enzyme carboxypeptidase E (CPE). We discovered novel molecular mechanisms of protein trafficking to the regulated secretory pathway and identified players and mechanisms that control secretory granule biogenesis and transport in endocrine and neuroendocrine cells and neurons. Furthermore, my lab has identified a new trophic role of CPE in neuroprotection, anti-depression, neurogenesis and stem cell differentiation, independent of its enzymatic activity. Recently, we discovered a novel N-terminal truncated isoform of carboxypeptidase E (CPE-ΔN) that is expressed primarily during embryonic brain development in mice, and highly expressed in metastatic tumor cells. We found that CPE-ΔN acts in the nucleus and promotes expression of genes involved in proliferation and migration of embryonic neurons and cancer cells. We are currently studying the role of CPE and CPE-ΔN in neurodevelopment. Both CPE and CPE-ΔN mRNA levels are higher in malignant tumor cells, and CPE mRNA is elevated in secreted exosomes of cancer patients compared to healthy controls, suggesting its potential use as a biomarker. Using cell lines, primary cell cultures, and mouse models, our research has provided a better understanding of diseases related to defects in hormone and neuropeptide targeting, neurodegenerative diseases, memory and learning, diabetes, obesity and cancer.

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