Zimmerman Program on the Biology of VWD

齐默尔曼 VWD 生物学计划

基本信息

  • 批准号:
    10584527
  • 负责人:
  • 金额:
    $ 262.95万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-03-15 至 2025-02-28
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY: OVERALL This Program Project Grant on remaining critical issues concerning the molecular and biologic control of von Willebrand factor in von Willebrand disease. This PPG is comprised of 4 projects and 3 cores that are all focused on von Willebrand disease and mechanisms causing its dysfunction, increased clearance or increased synthesis, and the role carbohydrate modification play in VWF biology. While this represents a new PPG application, this PPG makes use of the samples and biodata from the pre-existing PPG on historically diagnosed subjects and an R01 grant on new VWD subjects recruited prospectively. Project 1 includes aims to define longitudinal changes in VWF concentration and changes in semiquantitative bleeding assessment during follow-up intervals, the fidelity of the diagnosis of type 2 VWD, the frequency of antibodies to VWF in type 3 VWD, and the development of animal models of VWD and VWD variants. Subjects with low von Willebrand factor (LVWF), and type 1 or 3 VWD with no sequence variants will be studied in Core B with full genome sequencing. Abnormalities identified will be sought in their family members through Project 1 and the mechanism studied by projects 1, 2, 3, or 4 based on candidate pathway. Project 2 will define the role of carbohydrate modification of VWF through determination of N- and O-glycan profiles, study the glycan differences in plasma, endothelial and platelet VWF, and racial differences using MS-glycomic and glycoproteomic approaches. Model systems will be set up in mice to mirror the changes found in human mechanisms. Project 3 will examine the upstream regulatory control as a mechanism causing VWD. The cell biology of VWF will be studied using BOECs obtained from patients with VWD and used to examine the role of promoters and enhancers. Genetically engineered mice will study the mechanisms by which clearance receptors alter VWF concentration. Project 4 will study the transcription regulation of VWF and the inhibition with microRNAs. This project will also examine the role of epigenetics in modulating plasma VWF and the effect of chronic inflammation on these mechanisms. There are three cores to support this PPG. Core A is the administrative core that will facilitate exchange of information, data, and patient samples and biodata. It will also oversee the 10 Primary Clinical Centers that will be following our enrolled subjects. Core B will be doing whole genome sequencing of subjects with very low or absent VWF that have had normal VWF sequencing. Core C will develop animal models for each of the projects to further their studies on VWD mechanisms. Together these studies will comprehensively study unique mechanisms that lead to reduced or abnormal VWF in VWD.
项目总结:总体

项目成果

期刊论文数量(25)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Desmopressin responsiveness by age in type 1 von Willebrand disease.
1 型冯维勒布兰德病中不同年龄的去氨加压素反应。
  • DOI:
    10.1002/rth2.12354
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    4.6
  • 作者:
    Goldberg,Nicola;Nisenbaum,Rosane;Song,Hong;Lillicrap,David;Teitel,Jerome;James,Paula;Sholzberg,Michelle
  • 通讯作者:
    Sholzberg,Michelle
Investigating the clearance of VWF A-domains using site-directed PEGylation and novel N-linked glycosylation.
  • DOI:
    10.1111/jth.14785
  • 发表时间:
    2020-06
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Fazavana J;Brophy TM;Chion A;Cooke N;Terraube V;Cohen J;Parng C;Pittman D;Cunningham O;Lambert M;O'Donnell JS;O'Sullivan JM
  • 通讯作者:
    O'Sullivan JM
New developments in von Willebrand disease.
  • DOI:
    10.1111/bjh.16681
  • 发表时间:
    2020-11
  • 期刊:
  • 影响因子:
    6.5
  • 作者:
    Fogarty H;Doherty D;O'Donnell JS
  • 通讯作者:
    O'Donnell JS
von Willebrand Factor Antigen, von Willebrand Factor Propeptide, and ADAMTS13 in Carotid Stenosis and Their Relationship with Cerebral Microemboli.
  • DOI:
    10.1055/s-0040-1715440
  • 发表时间:
    2021-01
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Murphy SJX;Lim ST;Hickey F;Kinsella JA;Smith DR;Tierney S;Egan B;Feeley TM;Murphy SM;Collins DR;Coughlan T;O'Neill D;Harbison JA;Madhavan P;O'Neill SM;Colgan MP;O'Donnell JS;O'Sullivan JM;Hamilton G;McCabe DJH
  • 通讯作者:
    McCabe DJH
Pregnancy and delivery in women with von Willebrand disease.
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ROBERT R MONTGOMERY其他文献

ROBERT R MONTGOMERY的其他文献

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{{ truncateString('ROBERT R MONTGOMERY', 18)}}的其他基金

Project 1: Molecular Impact of VWF on Clinical VWD
项目 1:VWF 对临床 VWD 的分子影响
  • 批准号:
    10113376
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Project-004
项目-004
  • 批准号:
    10584541
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Zimmerman Program on the Biology of VWD
齐默尔曼 VWD 生物学计划
  • 批准号:
    10379431
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Project-004
项目-004
  • 批准号:
    10379439
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Project 1: Molecular Impact of VWF on Clinical VWD
项目 1:VWF 对临床 VWD 的分子影响
  • 批准号:
    10379435
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Project 1: Molecular Impact of VWF on Clinical VWD
项目 1:VWF 对临床 VWD 的分子影响
  • 批准号:
    10584533
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Zimmerman Program on the Biology of VWD
齐默尔曼 VWD 生物学计划
  • 批准号:
    10113367
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Core A: Administrative Core
核心A:行政核心
  • 批准号:
    10379432
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Zimmerman Program on the Biology of VWD
齐默尔曼 VWD 生物学计划
  • 批准号:
    9891082
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:
Core A: Administrative Core
核心A:行政核心
  • 批准号:
    10113373
  • 财政年份:
    2019
  • 资助金额:
    $ 262.95万
  • 项目类别:

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