SPUR 2019: Induced pluripotent stem cell derived cardiomyocyte models of human cardiovascular disorders

Background

Advances in induced pluripotent stem cell (iPSC) technology allow for reprogramming of adult somatic cells into stem cells from which patient-specific (and thus disease-specific) cardiomyocytes (CM) can be derived. The impact of this technology has far-reaching implications, ranging from drug discovery, pre-clinical drug screening, mechanistic understanding of disease processes, and advances in personalized medicine. Specifically human iPSC-CMs offer a unique model system to study phenotypic variation in Long QT Syndrome (LQTS), by allowing for direct comparisons of gene expression in human cardiac cells derived from family members who share the same mutation, but manifest severe versus mild symptoms. However, the potential of iPSC technology to answer this and other crucial research questions is limited by several technological barriers. For example, human iPSC-CMs in culture behave more like embryonic than mature myocytes and thus may not recapitulate key features of childhood or adult-onset disease. The overall goal of this proposal is to overcome the maturational hurdles in order to design a valid iPSC-CM model system for the study human arrhythmia disorders. This proposal utilizes cutting-edge technological approaches that will advance the field of cardiovascular medicine in a very practical manner.

The stipend for this SPUR project is funded by an American Heart Association grant awarded to Dr. Stavros Drakos, MD, PhD.

Student Role

The student will be responsible for differentiating stem cells into beating myocytes and will learn basic tissue culture techniques. The student may be involved in designing systems to improve the maturation of cardiomyoyctes in culture. In addition, the student will perform biochemical and molecular biology assays, including single cell RNA-seq experiments and analyses. The student will be paired with one or two post-doctoral fellows who will provide daily mentoring and support.

Student Learning Outcomes & Benefits

The student will gain exceptional experiences in different areas of basic and translational biomedical research. She/he will have an opportunity to gain insights into arrhythmia disorders, biochemical and molecular regulation of cardiac ion channels. The student will have plenty of hands-on involvement in conducting laboratory research and learn a great deal about stem cell models of human disease. This research opportunity is well suited for student who would like to pursue a medical career and research in biomedical science (MD/PhD). The learning experience from this project will help and encourage the undergraduate student to prepare for a research related career and professional development to become a scientist and/or physician.

Martin Tristani-Firouzi
Professor

Pediatrics
School of Medicine

We will develop the student's research capabilities with several measures:

  1. Scientific Training. Our technical training of the student in this project will focus on confocal microscopy, image processing and 3D reconstruction of tissue microstructure. We will also train the student in biochemical and molecular biology techniques and analyses, including single cell RNA-Seq analyses.
  2. Presentation Skills. The student will present her/his research in the weekly lab meetings with fellow students and post-doctoral associates. She/he will report on her/his progress and present relevant publications of others on a regular basis. Also, the student will participate in the monthly Research in Progress Seminar Series at the CVRTI.
  3. Increasing Personal Responsibility. We will execute an iterative approach to increase the personal responsibility of the student. Initially, we will provide rapid feedback on all aspects of this project. We will guide design and preparation of publications and presentations. After this phase, the student will be increasingly enabled to independently perform experimental work, analyze scientific data and prepare publications.