Cohen-Karni lab receives $3.1 million grant to study DNA damage in cardiac unit

If there comes a day that we can successfully space travel, it could have effects on the functioning of our organs and their components, most specifically our DNA. But how do we know if DNA is damaged? DNA damage is the subject of Associate Professor Tzahi Cohen-Karni's research, for which his lab, along with the University of Pittsburgh Aditi Gurkar lab, recently received a $3.1 million grant from the National Institute of Health's National Heart, Lung, and Blood Institute (NHLBI). The Cohen-Karni lab, in the departments of Biomedical Engineering and Materials Science and Engineering, has been working on studying DNA damage in the cardiac unit since 2014.

"Damage to the DNA in the cells could be due to, let's say, chemotherapy as as part of cancer treatment, for example. Maybe sometime in the future we will travel in space, and space travel will have some effects of the similar DNA, and this may affect functionality of organs," Cohen-Karni hypothesized in an interview with The Tartan. "So this [work is capable of influencing] two extreme ideas like life over here on Earth and our day to day living and challenges, and maybe futuristic ideas like traveling in space."

Essentially, the cardiac tissue in our bodies is composed of cardiomyocytes and fibroblasts, cells that communicate with each other through electrical activity. This electrical activity is fluxes of ions such as sodium, potassium, and calcium across the cardiomyocyte cell membranes. When ions move, it changes the cell membrane potential, which causes the cardiomyocytes, and consequently the heart, to contract. Cohen-Karni's lab hypothesizes that these ion fluxes, or transients, will change depending on the damage to the cell and its DNA.

To test this hypothesis, the Cohen-Karni lab will generate organoids, miniature mimics of organs constructed of three-dimensional tissue cultures. These organoids are made from induced pluripotent stem cells, which are skin cells that are "taken back in time" to when they were stem cells. Once a stem cell, it can then redifferentiate into any kind of cell, such as the cardiomyocytes that the Cohen-Karni lab uses in their organoids.

To test their hypothesis, the lab will then examine the healthy cells and compare them to damaged cells. The researchers are creating materials to monitor the intracellular activity, tiny electrodes that can be 20 times smaller than the size of a cell.

This project is a highly collaborative one. The Cohen-Karni lab will be working alongside Aditi Gurkar's lab, which has many biological tools that will allow them to understand which cells are involved in which processes. The lab will also be working with Associate Professor of Electrical Computer Engineering Pulkit Grover. There is also a large amount of data to be processed in this project. Just one of Cohen-Karni's chips can send gigabytes of data every hour, and to process all of the data manually would be incredibly difficult. Grover will help sift through the data using machine learning and artificial intelligence methods to find the differences and changes between undamaged and damaged cells.

Adam Feinberg, a professor of Biomedical Engineering and Materials Science and Engineering, is assisting Cohen-Karni and Gurkar in creating highly reliable and reproducible tissues and cell cultures, as well as techniques to record the electrophysiology of cardiac patients. Carmel Majidi, professor of Mechanical Engineering, will be assisting in developing the sensors used to monitor intracellular activity and the like.

Cohen-Karni believes there are many applications of this research. "I think this tool will allow us to understand disease progression, or will allow us to develop the tools to follow cardiovascular disease on a dish, for example. And it will allow us to test interventions as well as in screening for drugs."

Cohen-Karni also believes it has the potential to be applied to environmental science, such as monitoring the effect of air quality on the human body. "Sometimes the air is not that great. So you can use devices and platforms to actually learn how environmental effects are or are not detrimental to the human body, under what circumstances they are or not. So it's more than just this single-ended project, to be honest, it's more of a launch [of an] effort."