Exploration of the cellular citrullome using novel mass spectrometry tools

使用新型质谱工具探索细胞瓜氨酸组

基本信息

批准号：
10248287
负责人：
Ari Salinger
金额：
$ 1.18万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2020-11-25
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10248287
关键词：
Abate Address Affinity Alzheimer&apos s Disease Amino Acids Arginine Autoimmune Process Biochemical Biological Markers Biomedical Research Biotin Cancer Center Cancer Model Cancerous Cells Charge Chemicals Citrulline Collaborations Crohn&apos s disease Detection Directories Disease Early Diagnosis Environment Event Goals Heart Diseases Histones Human Inflammatory Intestines Lesion Link MCF10A cells Malignant Neoplasms Mass Spectrum Analysis Massachusetts Methods Modeling Mus Patients Pattern Peptides Play Positioning Attribute Post-Translational Protein Processing Protein-arginine deiminase Proteins Proteome Proteomics Recurrence Regulation Research Role Sampling Science Scientist Screening for cancer Series Signal Pathway Signal Transduction Site Survival Rate Synthesis Chemistry Testing Therapeutic Thrombosis Tissue Banks Tissue Sample Tissues Tumor Bank Ulcerative Colitis Universities Up-Regulation Variant Visualization Xenograft Model base cell type citrullinated protein disease diagnosis early detection biomarkers extracellular human tissue innovation malignant breast neoplasm medical schools neutrophil novel novel diagnostics novel marker personalized medicine response specific biomarkers tandem mass spectrometry tool

项目摘要

ABSTRACT There is growing evidence linking cancers and other diseases to the dysregulation of arginine deimination, or citrullination. This small post-translational modification (PTM) abates the charge on the arginine sidechain changing the local chemical environment. I hypothesize that citrullination patterns are variant among cell types, including cancerous and inflamed tissue lines, and therefore represent specific biomarkers. On that account, the long-term goal of this proposal is to determine specific citrullinated arginine residues in order to make inferences on the role this PTM plays on various forms of breast cancer tissue and, consequently, to uncover unambiguous biomarkers for novel diagnostics. To explore this, I have synthesized various chemical probes which will select for citrulline residues. These probes are unique in that they can then be used to enrich, visualize, and quantify citrulline-containing peptides. Concerning the identity of specific sites of citrullination, this probe will be used in conjunction with tandem mass spectrometry. Proteomic samples will be prepared using tissue samples supplied by my collaborators as well as the University of Massachusetts Medical School Tissue and Tumor Bank. From here, I will begin to compile a directory of markers associated with various cancers, autoimmune, and inflammatory diseases.

抽象的越来越多的证据表明癌症和其他疾病与精氨酸脱亚胺调节失调有关，或瓜氨酸化。这种小的翻译后修饰 (PTM) 减少了精氨酸侧链上的电荷改变当地的化学环境。我假设瓜氨酸化模式在细胞类型之间是不同的，包括癌变和发炎的组织系，因此代表特定的生物标志物。就此而言，该提案的长期目标是确定特定的瓜氨酸精氨酸残基，以便做出推论该 PTM 在各种形式的乳腺癌组织中发挥的作用，从而明确揭示用于新型诊断的生物标志物。为了探索这个问题，我合成了各种化学探针，它们将选择对于瓜氨酸残基。这些探针的独特之处在于它们可以用于富集、可视化和量化含有瓜氨酸的肽。关于瓜氨酸化特定位点的身份，该探针将用于与串联质谱联用。将使用提供的组织样本制备蛋白质组样本由我的合作者以及马萨诸塞大学医学院组织和肿瘤库提供。从在这里，我将开始编制与各种癌症、自身免疫性疾病和癌症相关的标记物目录。炎症性疾病。