The Endocrine Neoplasia Research Lab employs a combination of molecular, murine modeling, and live-cell imaging approaches to examine the underlying mechanisms of disrupted biochemical sensing behaviors in human endocrine tumors. Recently, in contrast to the prevailing clonal origin model, our group has shown that parathyroid adenomas driving primary hyperparathyroidism are comprised of functionally discrete and separable cellular subpopulations that respond differentially to extracellular calcium stimulation and which arise in many cases following polyclonal expansion of multiple independent progenitor cells within the parathyroid gland.

We are employing dynamic calcium response imaging at both the single cell and intact tissue level, in combination with transgenic mouse modeling to study how these newly identified cellular subpopulations drive the failure of appropriate calcium sensing in parathyroid disease. To examine cell-signaling behaviors in the native context of viable tumor tissue, we have developed a novel ex vivo imaging system that enables direct provocative testing of tumor reactivity to physiological agonist engagement at single-cell resolution. These methods form the foundation for our laboratory’s ongoing efforts to understand how perturbed biochemical signaling can contribute to the development of preneoplastic lesions in human endocrine neoplasia.