1998 B.S., Biochemistry - University of Geneva - Switzerland 2000 M.S., Biochemistry - University of Geneva - Switzerland 2005 Ph.D., Biochemistry - University of Geneva - Switzerland 2005-2014 Postdoctoral Fellow, Department of Neurology - UCSF School of Medicine, San Francisco, CA

Cellular Mechanisms of Neuroendocrine Secretion The ability to regulate the secretion of proteins is crucial to physiology, behavior and development. Eukaryotic cells express a constitutive secretory pathway that enables the immediate secretion of newly synthesized proteins. Neurons and endocrine cells, among others, also express a regulated secretory pathway, which enables them to store a subset of secretory proteins (e.g., neuropeptides, peptide hormones) into a class of vesicles that accumulate intracellularly and whose exocytosis can be triggered by the appropriate extracellular physiological stimulus. The vesicles that mediate this regulated secretion are called large dense core vesicles (LDCVs). LDCVs form at the trans-Golgi network where their soluble cargo aggregates to form a dense core, but the cellular mechanisms, and in particular, the cytosolic machinery that produces these secretory vesicles have remained elusive for many years. Recently, we have identified the adaptor protein AP-3 and VPS41 as part of the first cytosolic components that are necessary for biogenesis of LDCVs. Our work suggests that AP-3 recruits and concentrates specific transmembrane proteins onto LDCVs, and that VPS41 functions as a coat protein for AP-3, but we still do not understand how these components are regulated, how they cooperate in the cell, and how they influence the properties of regulated release. Our research aims at a better understanding of the molecular mechanisms that enable the formation of LDCVs. In addition, our work will assess the importance of the biogenesis step in predetermining the release properties of LDCVs. Finally, using the hypothalamus as a model system, we will manipulate the release mode of hypothalamic neuropeptides in vivo, thus determining whether their regulated secretion contributes to normal physiology and disease states such as obesity or type 2 diabetes. Our model systems include the rat neuroendocrine cell line (PC12), isolated mouse chromaffin cells, as well as transgenic mice. The techniques routinely used in the lab include cell culture, molecular biology, RNAi, Cas9/CRISPR genome-editing, confocal and TIRF microscopy, recombinant protein production combined with standard techniques in biochemistry.

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