Ruth Huttenhain, PhD, Assistant Professor, Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford

Research Description: The overarching goal of Dr. Huttenhain’s research is to study mechanisms of intracellular signal integration, with a specific focus on G protein-coupled receptors (GPCRs), by employing an interdisciplinary approach to probe, model, and predict how signaling network dynamics translate extracellular cues into specific phenotypic outputs. Our cells function like miniature computers, constantly sensing inputs from the environment through receptors on the cell surface. The receptors translate these inputs into intracellular signals, which are then processed through intricate, highly dynamic, and context-specific protein signaling networks that collectively define the cellular response. Given the complexity and dynamic state of signaling networks, our current understanding of their constituents and how they are spatiotemporally regulated as a result of a specific input is incomplete. In her new lab in the Department of Molecular and Cellular Physiology at Stanford University, they develop unbiased proteomic methods to map protein interaction and signaling networks, investigate their spatial organization within the cell, and understand their dynamic adaptations to various extracellular cues. While the technologies developed in her lab are disease-agnostic and thus applicable to various biological questions, they apply them to study the activation of GPCRs by endogenous and pharmacologically relevant ligands. GPCRs can detect a wide range of inputs, including hormones, neurotransmitters, odors, and light. However, the current understanding of intracellular responses to GPCR activation primarily focuses on a small set of known signal transducers, which fail to explain the remarkable physiological specificity of GPCR signaling. Signaling is orchestrated by additional proteins and molecular events in the receptor signaling network, functioning as signal transducers, organizers, or regulators that contribute to specialization of GPCRs at the cellular level. As drugs targeting GPCRs such as GLP-1RA, glucose-dependent insulinotropic polypeptide receptor (GIPR), and melanocortin-4 receptors (MC4R) have been approved for weight management/obesity, the research of our lab can (1) facilitate the identification of molecular events upon activation of these receptors that lead to weight loss and (2) provide an unbiased technology to test novel ligands targeting nutrition/obesityrelated GPCRs.