Cell Surface Phenotyping Human Primary Cells

人类原代细胞的细胞表面表型分析

基本信息

项目摘要

 DESCRIPTION (provided by applicant): Heart failure is an epidemic syndrome affecting 5.7 million Americans in which the weakened heart is unable to supply sufficient blood flow to the body. Approximately 10% of these patients will fail to respond to medical therapy and progressively worsen to develop advanced heart failure, for which the only definitive therapy is cardiac transplantation. As the supply of suitable donor hearts is limited to ~2000 per year in the US, the current and future care of advanced heart failure patients requires therapeutic alternatives. For some patients, mechanical circulatory support in the form of an implantable pump device can provide short- or long-term support, and in 1-2% of recipients, the heart improves to the point where the pump can be removed, termed myocardial recovery. Currently, it is not possible to predict which heart failure patients will respond to medical therapy alone, which will benefit from device support, and which have no potential for recovery. For device recipients, quantifying myocardial recovery to inform if, and when, to explant the device requires invasive testing. Thus, our long range goals are to develop novel strategies to identify patients with potential for recovery and develop non-invasive methods to monitor disease progression and recovery more precisely. In the short-term, our focus is on the development of novel cell surface markers to address these goals. Our previous studies of human cells in culture have successfully applied a mass spectrometric approach to capture and identify extracellular domains of cell surface glycoproteins, termed Cell Surface Capture (CSC). The proposed work extends these efforts and focuses on the implementation of innovative approaches to improve the CSC to enable identification and quantitation of cell surface proteins from live patient cells, as for many human diseases and syndromes like advanced heart failure, it is not possible to model the disease phenotype in vitro, and access to primary cells is severely limited. The current CSC requires 100 million cells. The studies outlined in this application are designed to develop a "microscale-CSC (µCSC)" to reduce the amount of starting material required by 10-fold. The specific goals of this application are to use new bioconjugation reagents and an innovative processing pipeline to develop µCSC and to expand its scope to capture a broader class of cell surface proteins with greater sequence coverage for improved quantitation (Aim 1); apply µCSC during in vitro cardiomyocyte differentiation from pluripotent stem cells and on cells isolated from human hearts (Aim 2); and apply µCSC to primary heart cells from patients with varying degrees of myocardial recovery (Aim 3). The identification of new markers and generation of reagents for identifying human cardiomyocytes with distinct developmental phenotypes will enable future mechanistic studies to determine the stages and molecular characteristics of cells amenable to repair. Once validated on primary heart cells derived from clinical samples, the technological advances resulting from the proposed studies will be widely applicable to researchers across a wide range of fields, from stem cell biology to cancer and patient diagnostics.


项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cell Surface Proteomics of N-Linked Glycoproteins for Typing of Human Lymphocytes.
  • DOI:
    10.1002/pmic.201700156
  • 发表时间:
    2017-10
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Haverland NA;Waas M;Ntai I;Keppel T;Gundry RL;Kelleher NL
  • 通讯作者:
    Kelleher NL
Cell-autonomous lipid-handling defects in Stargardt iPSC-derived retinal pigment epithelium cells.
  • DOI:
    10.1016/j.stemcr.2022.10.001
  • 发表时间:
    2022-11-08
  • 期刊:
  • 影响因子:
    5.9
  • 作者:
    Farnoodian, Mitra;Bose, Devika;Khristov, Vladimir;Susaimanickam, Praveen Joseph;Maddileti, Savitri;Mariappan, Indumathi;Abu-Asab, Mones;Campos, Maria;Villasmil, Rafael;Wan, Qin;Maminishkis, Arvydas;McGaughey, David;Barone, Francesca;Gundry, Rebekah L.;Riordon, Daniel R.;Boheler, Kenneth R.;Sharma, Ruchi;Bharti, Kapil
  • 通讯作者:
    Bharti, Kapil
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Rebekah L. Gundry其他文献

SurfaceGenie: A web-based application for prioritizing cell-type specific marker candidates
SurfaceGenie:基于网络的应用程序,用于优先考虑细胞类型特定标记候选物
  • DOI:
    10.1101/575969
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    M. Waas;S. Snarrenberg;J. Littrell;Rachel A. Jones Lipinski;P. Hansen;J. Corbett;Rebekah L. Gundry
  • 通讯作者:
    Rebekah L. Gundry
Correction to: Importance of evaluating protein glycosylation in pluripotent stem cell‑derived cardiomyocytes for research and clinical applications
  • DOI:
    10.1007/s00424-021-02566-7
  • 发表时间:
    2021-06-01
  • 期刊:
  • 影响因子:
    2.900
  • 作者:
    Maia I. Kelly;Mustafa Albahrani;Chase Castro;Ellen Poon;Bin Yan;Jack Littrell;Matthew Waas;Kenneth R. Boheler;Rebekah L. Gundry
  • 通讯作者:
    Rebekah L. Gundry
Cardiomyocyte Differentiation Promotes Cell Survival During Nicotinamide Phosphoribosyltransferase Inhibition Through Increased Maintenance of Cellular Energy Stores
烟酰胺磷酸核糖转移酶抑制期间心肌细胞分化通过增加细胞能量储存的维持来促进细胞存活
  • DOI:
  • 发表时间:
    2017
  • 期刊:
  • 影响因子:
    6
  • 作者:
    E. Kropp;Katarzyna A. Broniowska;M. Waas;Alyssa Nycz;J. Corbett;Rebekah L. Gundry
  • 通讯作者:
    Rebekah L. Gundry
The Albuminome as a Tool for Biomarker Discovery
蛋白组作为生物标志物发现的工具
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Rebekah L. Gundry;R. Cotter
  • 通讯作者:
    R. Cotter
INACTIVATION OF MANGANESE SUPEROXIDE DISMUTASE BY IRREVERSIBLE COVALENT OXIDATIVE MODIFICATION IN CARDIOVASCULAR DISEASE
  • DOI:
    10.1016/s0735-1097(20)31665-x
  • 发表时间:
    2020-03-24
  • 期刊:
  • 影响因子:
  • 作者:
    Daniel R. Anderson;Michael Duryee;Jake Walker;Johnathan H. Hall;Geoffrey M. Thiele;Lynell Klassen;Matt Zimmerman;Rebekah L. Gundry;Dahn L. Clemens
  • 通讯作者:
    Dahn L. Clemens

Rebekah L. Gundry的其他文献

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{{ truncateString('Rebekah L. Gundry', 18)}}的其他基金

Harnessing Glycoproteomics and Glycomics to Understand Cardiac Biology and Disease
利用糖蛋白组学和糖组学来了解心脏生物学和疾病
  • 批准号:
    10337288
  • 财政年份:
    2021
  • 资助金额:
    $ 38.13万
  • 项目类别:
Harnessing Glycoproteomics and Glycomics to Understand Cardiac Biology and Disease
利用糖蛋白组学和糖组学来了解心脏生物学和疾病
  • 批准号:
    10555323
  • 财政年份:
    2021
  • 资助金额:
    $ 38.13万
  • 项目类别:
Development of a next-generation glycomics platform to enable glycan structure analyses for precision medicine
开发下一代糖组学平台,以实现精准医学的聚糖结构分析
  • 批准号:
    10054508
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Development of a next-generation glycomics platform to enable glycan structure analyses for precision medicine
开发下一代糖组学平台,以实现精准医学的聚糖结构分析
  • 批准号:
    10239250
  • 财政年份:
    2020
  • 资助金额:
    $ 38.13万
  • 项目类别:
Cell Surface Proteins in Human Cardiomyocytes
人心肌细胞的细胞表面蛋白
  • 批准号:
    10037355
  • 财政年份:
    2019
  • 资助金额:
    $ 38.13万
  • 项目类别:
Cell Surface Proteins in Human Cardiomyocytes
人心肌细胞的细胞表面蛋白
  • 批准号:
    9027643
  • 财政年份:
    2016
  • 资助金额:
    $ 38.13万
  • 项目类别:
Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes
干细胞向心肌细胞分化中的表面蛋白
  • 批准号:
    8249072
  • 财政年份:
    2011
  • 资助金额:
    $ 38.13万
  • 项目类别:
Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes
干细胞向心肌细胞分化中的表面蛋白
  • 批准号:
    8449291
  • 财政年份:
    2011
  • 资助金额:
    $ 38.13万
  • 项目类别:
Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes
干细胞向心肌细胞分化中的表面蛋白
  • 批准号:
    8166085
  • 财政年份:
    2011
  • 资助金额:
    $ 38.13万
  • 项目类别:
Surface Proteins in the Differentiation of Stem Cells to Cardiomyocytes
干细胞向心肌细胞分化中的表面蛋白
  • 批准号:
    7572060
  • 财政年份:
    2009
  • 资助金额:
    $ 38.13万
  • 项目类别:

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