Black Family Stem Cell Institute

Heart and Muscle Regeneration

The adult heart is one of the least regenerative organs in the human body, among other reasons due to its lack of cardiac stem cells. As a consequence, heart disease remains the leading cause of mortality for both men and women, and congenital heart defects affect one percent of the human population.

Investigators at the Black Family Stem Cell Institute (BFSCI) are working to understand the underlying causes of heart disease with the goal of developing new therapeutic strategies.

Pluripotent stem cells have emerged as a new and powerful tool to study the molecular mechanisms of the complex genetics involved in adult and congenital heart defects. Furthermore, pluripotent stem cell-derived cardiomyocytes represent an unprecedented opportunity for cardiac cell therapy and regenerative medicine.

Parallel efforts in the field of cardiac regeneration include enhancing the regenerative potential of adult cardiomyocytes and reprogramming somatic cells toward the cardiac lineage. Laboratories at the Institute study how the cardiovascular system is established during development, and how errors in this process lead to congenital disease. Taking advantage of genome-wide association studies, BFSCI investigators uncover new mutations underlying heart defects, and use in vitro and in vivo models to study their function and to design targeted therapies. Advanced technologies such as CRISPR-guided genome editing, gene delivery via modified RNA, or tissue engineering enable Institute investigators to be at the forefront of discovery and to pursue the goal of better therapies for patients with heart disease.

Investigators with a major focus in cardiac biology and regeneration include:

Nicole C. Dubois, PhD

Nicole Dubois, PhD, received her PhD in Cell and Developmental Biology from the Swiss Institute for Experimental Cancer Research and the University of Lausanne with Andreas Trumpp, PhD. She did her postdoctoral training in the laboratory of Gordon Keller, PhD, at the University Health Network in Toronto with a focus on pluripotent stem cell biology and their differentiation to cardiovascular lineages. She is currently an Associate Professor in the Department of Cell, Developmental, and Regenerative Biology at the Icahn School of Medicine at Mount Sinai, the Black Family Stem Cell Institute, and the Mindich Child Health and Development Institute. Dr. Dubois' group studies early heart development and congenital heart disease using pluripotent stem cell differentiations and the mouse embryo as model systems.

Ongoing research interests include:

  • Understanding the molecular mechanisms of atrial-ventricular development
  • Exploring pluripotent stem cell differentiation to cardiovascular lineages
  • Looking at cardiac maturation and tissue engineering
  • Investigating long non-coding RNAs during cardiac development
  • Exploring cardiac toxicity of cancer drugs (LINCS project)

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Bruce D. Gelb, MD

Bruce Gelb, MD, is the Gogel Family Professor of Child Health and Development and Professor of Pediatrics and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, and he directs the Mindich Child Health and Development Institute. He is a co-leader of a National Heart, Lung, and Blood Institute-funded training program in molecular and cellular cardiology. Dr. Gelb’s research group studies the genetic causes of cardiovascular diseases of childhood, particularly focusing on congenital heart defects and inherited disorders of the Ras/microtubule-associated protein (MAP) kinase signal transduction pathway (called RASopathies). His group, working with the then Black Family Stem Cell Institute Director, Ihor Lemischka, PhD, generated the first human induced pluripotent stem cell (hiPSC) model of a cardiovascular trait (hypertrophic cardiomyopathy for Noonan syndrome with multiple lentigines).

Ongoing research interests include:

  • Understanding the pathogenesis of hypertrophic cardiomyopathy for RASopathies
  • Discovering novel therapies for hypertrophic cardiomyopathy for RASopathies
  • Understanding congenital heart defect pathogenesis due to histone modifier mutations

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Lior Zangi, PhD

Lior Zangi, PhD, is an Assistant Professor in Cardiology at the Icahn School of Medicine at Mount Sinai. He completed his education and training at the Weizmann Institute of Science and at Harvard University. He has established a new method, mRNA based, for gene delivery to promote cardiovascular regeneration. Dr. Zangi’s laboratory investigates cellular and organ level regenerative mechanisms that can contribute to new therapeutic approaches to repair and regenerate the heart following myocardial infarction. The Zangi lab's goal is to induce cardiac regeneration after myocardial infarction using a gene therapy approach with modified mRNA. Modified mRNA is an attractive and novel in vivo gene delivery method that allows high gene expression in a variety of organs, including the heart. The Zangi Laboratory will use modified mRNA to transiently change the non-regenerative gene expression profile of adult cardiac muscle to grant regenerative capacity to the adult heart after injury. The lab plans to investigate specific genes or signaling networks on both cellular (cell specific) and tissue (whole muscle) levels, using modified mRNA and other gene delivery approaches.

Ongoing research interests include:

  • Induce cardiomyocytes proliferation and survival by manipulating cardiomyocytes metabolic pathways
  • Use cardiac reprograming to induce cardiovascular regeneration
  • Employ long non-coding RNA to induce cardiac regeneration

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