John P. Cooke, Houston Methodist Research Institute - Radiation-Induced Skin Damage and Telomerase Therapy

On Houston Methodist Week: What are free radicals, and how are they affecting our cells?

John P. Cooke, professor of cardiovascular sciences, discusses this.

Faculty Bio:

Dr. John P. Cooke is the Chair of the Department of Cardiovascular Sciences at the Houston Methodist Research Institute, Director of the Center for Cardiovascular Regeneration, and Medical Director of the RNA Therapeutics Program in the Houston Methodist DeBakey Heart and Vascular Center in Houston, Texas.

He trained in cardiovascular medicine and obtained a Ph.D. in physiology at the Mayo Clinic. He was recruited to Harvard Medical School as an assistant professor of medicine. In 1990, he was recruited to Stanford University to spearhead the program in vascular biology and medicine, and was appointed professor in the Division of Cardiovascular Medicine at Stanford University School of Medicine, and associate director of the Stanford Cardiovascular Institute until his recruitment to Houston Methodist in 2013.

Dr. Cooke’s research program is focused on vascular regeneration, vascular cell identity and cell fate. The Cooke group aims to understand the mechanisms underlying epigenetic plasticity that are required for functional adaptation to cellular challenges. Innate immune signaling causes global changes in the expression and activity of epigenetic modifiers with metabolic coupling that favors an open chromatin configuration. The translational output of this work is vascular regeneration via therapeutic transdifferentiation using small molecules or mRNA.

Transcript:

Every day our cells are under attack from an enemy within – reactive oxygen species, also known as free radicals. Free radicals are generated by cell metabolism, by the very nature of burning calories. The DNA in a single cell takes tens of thousands of hits per day.

The good news is that our cells have outstanding DNA repair systems that fix the damage. They have to fix the damage, as the DNA is the code for the identity of the cell, and for its functions. In a surprising twist, we found recently that one such DNA repair protein is the enzyme called telomerase.

You may know it! Telomerase repairs the ends of the chromosome. These ends are a bit like the ends of a shoelace, holding the chromosome together. As cells divide, the telomere gets shorter, and at some point, the cells can’t divide anymore and become aged. Telomerase can repair the ends so that the cells can keep going.

Recently, we found that telomerase can also repair DNA damage throughout the length of the chromosome. We found that telomerase could repair the DNA damage caused by free radicals generated during aging.

Then we gave telomerase a tougher test. Could telomerase repair DNA damage due to radiation. We treated human skin cells, and human skin, with mRNA encoding telomerase. We saw that telomerase was generated by the skin cells and protected them from radiation induced DNA damage. That protection prevented radiation-induced aging and death of the skin cells. This work indicates that the unexpected effect of telomerase to repair DNA throughout the length of the chromosome can protect human cells from free radicals, aging, and radiation.

Read More:

[Houston Methodist] - New study shows mRNA therapy could protect patients from radiation-induced skin damage caused by cancer treatment