Abstract

This is a resubmission for the K24 Midcareer Investigator Award in Patient-Oriented Research (POR). The applicant, Dr. Phillip Yang, is a physician-scientist and Associate Professor of Medicine (Cardiovascular Medicine) at Stanford University. Over the past 10 years, Dr. Yang has developed an interdisciplinary translational expertise at the intersection of molecular/cellular imaging and stem cell biology. He has consolidated his expertise to train in POR in regenerative medicine, develop an independent POR career, and mentor the junior clinical investigators. To accomplish this objective, he has received independent research awards from the NIH, AHA, and CIRM related to clinical application of stem cells. Most notably, he received the NIH/NHLBI UM1 Cardiovascular Cell Therapy Research Network (CCTRN) grant, which is a 7-year (2012- 2019) $73M effort, consisting of 7 academic sites to design multi-center clinical trials of novel cell therapy. CCTRN will provide the overall framework to conduct POR and to mentor junior clinical investigators. Dr. Yang leads the effort at Stanford to conduct the CCTRN sponsored parent clinical trial, Combination Of c- kit cells and mesenchymal cells: a Novel, dual Cell study Evaluating Regenerative properties for Treatment in Chronic Heart Failure (CONCERT). CONCERT is a multi-center, randomized, double-blinded clinical trial designed to study the effects of 3 stem cel populations in 144 ischemic cardiomyopathy patients: 1) mesenchymal stem cells (MSCs), 2) ckit+ cardiac progenitor stem cells (CPCs), 3) combined MSC/CSCs, and 4) placebo. The CCTRN UM1 Award provides $350,000 per year in direct costs for POR in addition to the cost of conducting CONCERT. This K24 is designed to leverage the resource and infrastructure of CONCERT to allow an invaluable opportunity for Dr. Yang to augment his POR and mentor the junior investigators. In addition to conducting the CONCERT trial, Dr. Yang will recruit the CONCERT patients to undergo two ancillary studies to investigate the clinical utility of manganese-enhanced MRI (MEMRI) and iPSC-derived cardiomyocytes (iCMs). The MEMRI study will assess the direct effects of cell therapy on the peri-infarct region (PIR). The MEMRI data will be correlated with the clinical outcome to determine the ability to visualize the direct therapeutic effects of stem cells in real-time. The iCM study will assess the direct in vitro response of the patient-specific iCMs to cell therapy. Functional assays of the patient-specific iCMs will provide a high- resolution assessment of the individual response to cell therapy and potentially correlate with MEMRI. The K24 proposal will provide support for Dr. Yang's 25% FTE and supplies for MEMRI and iCM studies. Dr. Yang has over 10-year history of mentoring junior clinician scientists, postdoctoral fellows, medical students, graduate students, and undergraduates - all performing POR. This funding will provide protected time to augment and enhance Dr. Yang's ongoing POR and mentor new clinical investigators.

Public Health Relevance

This Award will enable the candidate to leverage the framework of NIH/NHLBI funded Cardiovascular Cell Therapy Research Network to advance his patient-oriented research career and training to mentor junior clinical investigators. The proposed research investigates the efficacy of a novel imaging technique and stem cell biology to better understand the role of regenerative medicine in heart failure, which is the leading diagnosis of hospital admission in the United States. Novel imaging technology, manganese-enhanced MRI, and pioneering stem cell biology, iPSC-derived cardiomyocytes, are investigated to assess their clinical diagnostic and predictive roles in cardiovascular regeneration.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL130553-02
Application #
9257462
Study Section
Special Emphasis Panel (MPOR (JA))
Program Officer
Huang, Li-Shin
Project Start
2016-04-15
Project End
2021-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
2
Fiscal Year
2017
Total Cost
$118,635
Indirect Cost
$8,788

  Institution

Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304