Identification and Characterization of Nutrient-Sensing Metabolite GPCRs

我的研究方向是分子内分泌学：细胞在分子水平上相互交流的方式。为了生存并发挥其预期的功能，邻近的细胞必须不断地感知环境条件和营养可用性的变化，并通过细胞功能的精细调整做出反应。营养状态信号，如蛋白质、脂肪、糖、代谢物和激素，通过激活细胞表面的特殊受体来协调这种动态通信。G蛋白偶联受体（GPCR）超家族由超过800个独特的细胞表面受体组成，这些受体能够检测这些不同的信号，从而不断适应环境条件和需求。我和我的学生试图了解这些受体在营养缺乏和营养过剩时如何控制细胞功能。在短期内，我们专注于这些受体的一个子集，即所谓的代谢物gpcr。我们的问题是(1)这些受体对细胞存活和代谢功能至关重要吗？(2)这些受体调节细胞功能的细胞机制是什么？为了回答这些问题，我们使用受体删除或添加技术研究多种激素分泌和敏感细胞类型（例如，肝脏，胰腺，大脑），并结合标准分子生物学实验室分析来测量不同代谢应激条件下的细胞健康和功能。利用这些手段，我们将回答生物学问题：细胞表面gpcr如何在环境胁迫下促进细胞营养感知和生存？这是细胞和整个动物生存的基本功能。通过比较和对比受体在各种细胞类型中的使用，这些研究将提供对营养检测的组织特异性机制的见解，并将强调那些跨越多个组织的基本机制，并代表代谢调节的基本过程。

***My research investigates molecular endocrinology: the ways in which cells communicate with one another on a molecular level. In order to survive and perform their intended functions, neighboring cells must continuously sense changes in environmental conditions and nutrient availability and respond through finely tuned alterations in cellular function. Nutrient status signals such as proteins, fats, sugars, metabolites, and hormones orchestrate this dynamic communication through activation of specialized receptors on the surface of cells. The G protein-coupled receptor (GPCR) superfamily constitutes greater than 800 unique cell-surface receptors capable of detecting these diverse signals in order to continuously adjust to environmental conditions and demand. My students and I seek to understand how these receptors control cell function during nutrient shortage and nutrient excess. In the short term, we are focusing on a subset of these receptors, the so-called metabolite GPCRs. We ask (1) are these receptors essential for cell survival and metabolic function? (2) What cellular mechanisms do these receptors use to modulate cell function? To answer these questions, we study multiple hormone-secreting and sensitive cell types (e.g., liver, pancreas, brain) using receptor deletion or addition techniques, in combination with standard molecular biology lab analyses to measure cellular health and function under different metabolic stress conditions. Using these means, we will answer the biological question: How do cell surface GPCRs contribute to cellular nutrient sensing and survival during environmental stress? a fundamental function for cells and whole animal survival. By comparing and contrasting receptor use in a variety of cell types, these studies will provide insight into tissue-specific mechanisms of nutrient detection and will highlight those essential mechanisms that span multiple tissues and represent fundamental processes in metabolic regulation.