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Miriam Stoeber is an Associate Professor in the Department of Cell Physiology and Metabolism at the University of Geneva. She started her SNSF Eccellenza-funded research group as an Assistant Professor in July 2019.
Miriam received her master’s degree at the École Supérieure de Biotechnologie de Strasbourg and obtained her PhD in biochemistry & cell biology at the ETH Zurich. As a master’s student in Prof. Sandy Schmid’s lab at The Scripps Research Institute in San Diego and during her time as a graduate student in Prof. Ari Helenius’ group at ETH, she identified new proteins that regulate cellular entry pathways (i.e. endocytosis) and developed a deep fascination for cellular organization and membrane trafficking.
In 2013, Miriam joined Kay Grünewald’s group at the University of Oxford for a short-term postdoc where she combined biochemical methods and cryo-electron microscopy to characterize the assembly and architecture of an endocytic protein coat termed caveolae. In 2014, she moved to the University of California San Francisco (UCSF) where she worked as a postdoc in the group of Prof. Mark von Zastrow. Here, she investigated the interplay between receptor trafficking and signaling of opioid receptors and developed novel nanobody-based biosensors and reporters to detect receptor activation with subcellular precision. Her group’s current research activities is about subcellular control of receptor signaling.
Subcellular Control of Receptor Signaling
G protein-coupled receptors (GPCRs), also called seven-transmembrane receptors, comprise nature’s largest receptor family and are activated by a remarkable diversity of ligands that include neurotransmitters, hormones, odorants, ions, and photons. GPCRs play essential roles in physiology and disease and represent the most common class of therapeutic targets.
An emerging principle in GPCR biology is that chemically distinct ligands that activate the same cognate receptor can produce different signaling responses. Ligand-selective signaling is motivating ongoing drug development campaigns, however, it remains largely unknown how exactly distinct ligands drive discrete signaling pathways in the cellular context.
In our laboratory, we are studying how the precise subcellular location of receptor signaling defines ligand-selective effects. In particular, we focus on the physiologically and pharmacologically important GPCR family called opioid receptors. Opioid receptors are the target of opioid drugs (e.g. morphine or fentanyl) that are the most effective agents known for alleviating pain but produce significant toxicity and have high abuse potential. Previously we have shown that opioid drugs differ from endogenous peptides in the cellular location at which they drive receptor activation. It suggests that some drug-specific effects and abuse responses may be explained by what cellular receptor pool a certain drug is interacting with.
Now we aim to unravel how location-specific signaling contributes to drug action and pathology. We combine cutting edge live-cell microscopy, novel nanobody-based biosensors, pharmacology, neurobiology, and genomic approaches to dissect clinically important GPCR signaling systems in the cellular context.