A McAllister team from Li Qian’s Lab has published new research in Cell Stem Cell that holds promise to “mend a broken heart” by describing how to directly reprogram human fibroblasts into cardiomyocytes. The research described in the paper, “Single Cell Transcriptomic Analyses of Cell Fate Transitions during Human Cardiac Reprogramming”, is the first to develop a stable, reproducible, minimalistic platform for this reprogramming. Moreover, by taking advantage of the latest single-cell technologies and mathematical modeling, Li Qian, PhD, and her group have produced a high-resolution molecular roadmap to guide precise and efficient reprogramming.
The work is a crucial advance because fibroblasts form scar tissue that leads to permanent loss of heart function after a heart attack, while cardiomyocytes form the heart muscle that pumps blood throughout the body. A long term therapeutic goal is to be able to quickly reprogram fibroblasts in human patients with myocardial infarction so that new heart muscle forms to recover heart function. Victoria Bautch, PhD, Co-Director of MHI and Chapin Distinguished Professor of Biology, says that “It is intriguing and important that the process of reprogramming human fibroblasts differs in significant ways from murine reprogramming, as shown in the new work from the Qian lab. Qian and her team’s cutting-edge research embodies the mission of McAllister Heart Institute to integrate basic cardiovascular scientific discoveries with translational and clinical outcomes to improve human health.”
The supportive, team-oriented research environment at McAllister fosters such innovative research and helps support the next generation of young scientists. Qian is Associate Director of MHI and Associate Professor of Pathology and Laboratory Animal Medicine, and has made numerous seminal discoveries since setting up her independent research program in MHI 7 years ago. The paper’s first author, Yang Zhou, PhD, started this year as Assistant Professor at the University of Alabama at Birmingham. Another co-author, Ben Keepers, initially worked on the project during a rotation at Qian Lab 3 years ago. His enjoyable and productive work led him to join Qian Lab long-term, where he is now working on the next step– generating a “foot-print free” approach using CRISPRi system rather than viral delivery of GMT133 for human cardiac reprogramming. Ben is currently a trainee in MHI’s Integrative Vascular Biology Training Program, an NIH-funded initiative that exposes students to the latest concepts in cardiovascular biology in collaboration with faculty from 12 UNC departments.
McAllister creates an environment where researchers can thrive in obtaining key funding to support their work. The Cell Stem Cell research was supported by National Institutes of Health, National Heart, Lung, and Blood Institute, the American Heart Association, a Jefferson Pilot Award, as well as internal UNC funds and generous gifts from Dr. Hugh “Chip” McAllister and Cecil Sewell. MHI faculty and trainees have successfully acquired outside funding from the NIH, the American Heart Association, the National Science Foundation (NSF), and the Dept. of Defense, that totals almost $7M for 2019.
McAllister Heart Institute is a center for innovation in cardiovascular research. The vibrant, multidisciplinary environment at MHI supports faculty, postdocs, and other trainees to perform cutting-edge research and help translate these innovative discoveries into clinical practice.