CORE D - Proteomics Core

Information

  • Research Project
  • 10171427
  • ApplicationId
    10171427
  • Core Project Number
    P01HL131474
  • Full Project Number
    2P01HL131474-06
  • Serial Number
    131474
  • FOA Number
    PAR-18-405
  • Sub Project Id
    9964
  • Project Start Date
    7/15/2016 - 7 years ago
  • Project End Date
    5/31/2026 - a year from now
  • Program Officer Name
    SARKAR, RITA
  • Budget Start Date
    5/1/2021 - 3 years ago
  • Budget End Date
    4/30/2022 - 2 years ago
  • Fiscal Year
    2021
  • Support Year
    06
  • Suffix
  • Award Notice Date
    8/26/2021 - 2 years ago

CORE D - Proteomics Core

SUMMARY The Proteomics Core facility (Core D) will support the proposed projects to address the central hypothesis of the program; protein glycosylation and glycoprotein remodeling alter the coagulopathy and inflammation of sepsis. Core D uses state-of-the-art mass spectrometry to analyze plasma and cellular proteomes in sepsis. Core D has made essential contributions to the progress of the P01 during the first funding cycle, providing important findings in support of all three research projects, and findings that led to two publications, one in Nature Communications. The Specific Aims of Core D are to: 1) Assess time and pathogen-dependent changes to the Plasma Proteome resulting from sepsis, 2) Characterize the time and pathogen-dependent remodeling of the vascular surface proteome, and 3) Determine the molecular basis of enhanced consumption coagulopathy exhibited during Gram- negative sepsis. Aim 1 focuses on plasma proteomics for all three projects. Project 1 will use plasma proteomics to identify specific glycosidases, their glycoprotein substrates, and endocytic lectin receptors and determine their impact of their homeostatic regulation on the coagulopathy and inflammation of sepsis. Project 2 will use plasma proteomics to identify components and mechanisms of both the pathogen and host determining virulence and sepsis pathogenesis and determine their utility in the stratification and prognosis of experimental and human sepsis. Project 3 will use plasma proteomics to determine vascular surface marker shedding into circulation in murine models of sepsis, and their impact in the coagulopathy and inflammation of sepsis while identifying mechanistic links that may enable human disease stratification and prognosis. Aim 2 focuses on characterizing the vascular surface proteome in support of Project 3. This work will characterize organ-specific changes to vascular cell surface proteomes and determine their impact in the coagulopathy and inflammation of sepsis and their utility in the stratification and prognosis of human disease. Aim 3 will support Project 2 in seeking to characterize the enhanced consumption coagulopathy exhibited during Gram-negative sepsis. This work will use activity-based proteomics and standard protein fractionation analysis to identify bacterial function(s) responsible for the observed FXI-stimulatory activity present in SC/ST/EC supernatants; and determine its role in the elevated consumption coagulopathy in Gram-negative sepsis and possible utility in the stratification and prognosis of human disease.

IC Name
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
  • Activity
    P01
  • Administering IC
    HL
  • Application Type
    2
  • Direct Cost Amount
    391947
  • Indirect Cost Amount
    215672
  • Total Cost
  • Sub Project Total Cost
    607619
  • ARRA Funded
    False
  • CFDA Code
  • Ed Inst. Type
  • Funding ICs
    NHLBI:607619\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    HLBP
  • Study Section Name
    Heart, Lung, and Blood Initial Review Group
  • Organization Name
    SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
  • Organization Department
  • Organization DUNS
    020520466
  • Organization City
    LA JOLLA
  • Organization State
    CA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    920371005
  • Organization District
    UNITED STATES