The development of mass spectrometry for Clinical Glycomics

描述（由申请人提供）：我们将开发方法和工具来分析人体体液中的聚糖，从而发现疾病的标志物。癌症是一种已知伴随异常糖基化的疾病。由病变细胞脱落的糖蛋白将被收集其多糖含量，并被分析以获得疾病标志物。这种方法代表了疾病标志物发现的新范式。它将主要关注作为疾病标志物的聚糖，而首先忽略相关蛋白的身份。这种方法将是多方面的，主要是糖中心的；它对比和补充了目前广泛研究的以蛋白质组为中心的方法。在这个过程中，我们将开发一套基于质谱的临床糖组学工具。这些工具将用于观察两种人体液体，血清和泪液中疾病糖基化的变化。这些液体是根据我们的合作者的需要选择的，这些疾病包括卵巢癌和眼红斑痤疮，但对乳腺癌和前列腺癌的血清和其他干眼病的泪液有直接的影响。虽然疾病标志物将是这些研究的未来成果，但它们不会是本项目的唯一重点。相反，我们还将开发工具，供我们的合作者使用，以发现这些疾病的标志物，并为在临床中使用质谱法进行糖糖分析奠定基础。

DESCRIPTION (provided by applicant): We will develop the methods and tools that will profile glycans in human fluids to enable the discovery of markers for diseases. Cancer is a disease known to accompany aberrant glycosylation. Glycoproteins shed by diseased cells will be harvested for their glycan content and profiled to obtain disease markers. This approach represents a new paradigm for disease marker discovery. It will focus primarily on the glycans as disease markers while neglecting, at first, the identity of the associated proteins. This approach will be multifaceted and primarily glycocentric; it contrasts and complements the proteome-centered approaches currently under extensive investigations. In this process, we will develop a set of mass spectrometry-based tools for clinical glycomics. These tools will be used to observe changes in glycosylation of diseases in two human fluids, sera and tear. The fluids are chosen by the needs of our collaborator in diseases that include ovarian cancer and ocular rosacea but will have direct implications in breast cancer and prostate cancer for sera and other dry eye diseases for tear fluids. While disease markers will be the future outcome of these studies, they will not be the only focus of this project. Instead we will also develop the tools that will be used by our collaborators to discover markers for these diseases and lay the foundation for the use of mass spectrometry in clinics for glycomic analyses.