MicroRNA Biomarkers of Allograft Rejection and Cardiac Allograft Vasculopathy in Cardiac Transplantation

Information

  • Research Project
  • 10085675
  • ApplicationId
    10085675
  • Core Project Number
    K23HL143179
  • Full Project Number
    5K23HL143179-02
  • Serial Number
    143179
  • FOA Number
    PA-19-119
  • Sub Project Id
  • Project Start Date
    7/1/2020 - 4 years ago
  • Project End Date
    6/30/2025 - 6 months from now
  • Program Officer Name
    SCOTT, JANE
  • Budget Start Date
    7/1/2021 - 3 years ago
  • Budget End Date
    6/30/2022 - 2 years ago
  • Fiscal Year
    2021
  • Support Year
    02
  • Suffix
  • Award Notice Date
    7/7/2021 - 3 years ago

MicroRNA Biomarkers of Allograft Rejection and Cardiac Allograft Vasculopathy in Cardiac Transplantation

Project Summary This purpose of this research proposal is to support the development of Palak Shah, MD, MS into an independent investigator, and to conduct novel, transformative explorations of circulating, cell-free microRNAs (ccf-miR) in heart transplantation. Circulating, cell-free miRs may serve as non-invasive biomarkers of allograft rejection and cardiac allograft vasculopathy (CAV), two leading causes of morbidity and mortality in heart transplant recipients. The candidate, Dr. Shah, has demonstrated his long-standing commitment to academic medicine by pursuing a Masters in Clinical and Translational Research. As a junior faculty member, Dr. Shah?s early work has focused on the identification of blood-based biomarkers to better manage patients with advanced heart failure, left ventricular assist devices (LVADs), and following transplantation. The K23 award will extend initial experiences in genomic assay development and biomarker validation to include: 1) isolation of ccf-miRs from blood samples and preparation of biospecimens for next-generation sequencing; 2) sequence data alignment and bioinformatic interpretation of sequence data; and 3) the development of a clinical panel of ccf-miR biomarkers to detect allograft rejection using biostatistical analyses that combine transcriptomic and clinical data. To accomplish these goals, a comprehensive career development plan has been formulated that includes both formal coursework and mentored research under the close supervision and guidance of a senior team of experienced mentors. The mentorship team includes multiple thought-leaders with detailed expertise relevant to the career goals of the applicant: Christopher O?Connor, MD (clinical validation of heart failure biomarkers and trial design), Jun Zhu, PhD (RNA-sequencing and bioinformatic analyses), Hannah Valantine, MD (cardiac transplantation and genomic biomarkers), and Christopher deFilippi, MD (cardiovascular biomarker discovery and validation). The specific aims of the research are to 1) Determine the ccf-miR transcriptome of cardiac transplant recipients to identify novel miR biomarkers that distinguish cardiac allograft rejection; 2) Distinguish ccf-miR biomarkers of chronic rejection manifest as cardiac allograft vasculopathy. Previous groundwork and training have prepared Dr. Shah to successfully undertake the proposed research, and to transition him into an independent investigator. The study results are expected to establish a framework for using ccf-miRs as diagnostic biomarkers of allograft rejection and CAV. Once clinically validated in a future multicenter study, ccf-miRs can be used to non-invasively diagnose allograft rejection and CAV in heart transplant patients.

IC Name
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
  • Activity
    K23
  • Administering IC
    HL
  • Application Type
    5
  • Direct Cost Amount
    172000
  • Indirect Cost Amount
    13760
  • Total Cost
    185760
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    837
  • Ed Inst. Type
  • Funding ICs
    NHLBI:185760\
  • Funding Mechanism
    OTHER RESEARCH-RELATED
  • Study Section
    MPOR
  • Study Section Name
    NHLBI Mentored Patient-Oriented Research Review Committee
  • Organization Name
    INOVA HEALTH CARE SERVICES
  • Organization Department
  • Organization DUNS
    054427455
  • Organization City
    Fairfax
  • Organization State
    VA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    220314868
  • Organization District
    UNITED STATES