CYCLOPHOSPHAMIDE AND TASTE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 环磷酰胺是最常用的化疗处方药，但与其他化疗药物一样，它也有许多副作用，如味觉能力改变或丧失，可导致营养不良和恢复较差。我们感兴趣的是什么导致了化疗导致味觉功能的变化。我们假设环磷酰胺破坏了新的味觉细胞的干细胞或前体细胞的DNA。细胞周期会停止，直到DNA修复完成。一旦修复，干细胞就会产生新的味觉细胞，味觉就会恢复。为了验证这一假设，我们提出了四个具体的目标，这些目标将使用从行为技术到分子生物学的一系列工具，使用小鼠模型。我们将使用行为和分子方法来评估环磷酰胺引起的功能障碍的广度。此外，我们建议研究该药物如何扰乱成人味觉干细胞的功能以及该系统如何恢复，包括SOX基因家族的作用。以前在这方面还没有做过任何工作。我们的工作旨在填补对化疗这种往往具有破坏性的副作用的理解方面的一些空白。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cyclophosphamide is the most commonly prescribed drug used for chemotherapy, but it like other chemotherapy drugs, has many adverse side effects such as altered or lost taste sensory abilities which can lead to malnutrition and poorer recovery. We are interested in what causes the changes in taste functions due to chemotherapy. We hypothesize that cyclophosphamide damages the DNA of stem cells or progenitor cells for new taste sensory cells. The cell cycle is arrested until the DNA repair is complete. Once repaired, new taste sensory cells are generated from the stem cells and taste sensations recover. To test this hypothesis, we propose four Specific Aims that will use a range of tools from behavioral techniques to molecular biology using a mouse model. We will use behavioral and molecular methods to assess the breadth of functional disruptions caused by cyclophosphamide. In addition we propose to study how the drug disrupts adult taste stem cell functioning and how the system recovers, including the role of the Sox family of genes. No previous work has been done in this area. Our work aims to fill some voids in the understanding of this often devastating side effect of chemotherapy.