Aditi Gurkar, PhD, Awarded NIH R01 Grant to Study Telomere Damage and Heart Health
August 15, 2024
Aditi Gurkar, PhD, principal investigator of the Gurkar Laboratory at the University of Pittsburgh Aging Institute was awarded a National Institute’s of Health R01 grant in March 2024 to study “Telomere Dysfunction Driven Molecular Outputs in the Cardiac Unit.”
The research is designed to better understand how damage to telomeres in the cardiomyocytes and other cells of the heart caused by environmental factors affect heart health and drive cardiovascular disease processes.
Dr. Gurkar is an assistant professor of Medicine in the UPMC Division of Geriatric Medicine. Dr. Gurkar's lab studies biological aging and aims to understand mechanistically how and why individuals age differently at the molecular and cellular level. The goal of the lab’s research is to be able to predict how an individual will age biologically, and armed with this knowledge, allow for the design of personalized interventions and programs for more healthy aging and an extended healthspan.
About the Study and Its Objectives
Telomeres are protective caps at the ends of chromosomes that prevent damage to genetic material during cell division. Over time, and due to environmental exposures, telomeres can become damaged, leading to cellular aging and dysfunction.
Cellular oxidative stress is one important driver of telomere damage. Oxidative stress occurs when there is an imbalance between free radicals and the body's ability to neutralize them with antioxidants. This type of stress, particularly when it persists over long periods, has been shown to affect heart and vascular health, and can be a contributor to the formation of heart disease.
Dr. Gurkar's research is designed to investigate the mechanisms by which oxidative stress-induced telomere damage affects the function of heart cells, particularly the cardiomyocytes and cardiac fibroblasts.
Prior work on the subject by Dr. Gurkar and her collaborators suggests that oxidative stress leads to cellular aging in the heart, which is not solely due to telomere shortening but also due to direct oxidative damage to the cells and their functional capacity.
“This has been very difficult to study in the past because we did not have a precise and repeatable way to create telomere damage for specific durations and in specific types of cells,” says Dr. Gurkar. “However, we’ve come up with a new approach that allows us to do just that.”
To study this, Dr. Gurkar's team along with collaborators Patricia Opresko, PhD, from the University of Pittsburgh, and Marcel P. Bruchez, PhD, and Bruce Armitage, PhD, both from Carnegie Mellon University, developed a new chemoptogenetic tool that can create oxidative damage directly at the telomeres. This will allow Dr. Gurkar’s team to see how such damage impacts heart cells over time.
“We have also developed the means by which we can study how telomere damage in one type of cell – in this case the cardiomyocytes – may impact the function of the cardiac fibroblasts, and overall heart health and functionality,” says Dr. Gurkar. “The tools and research we are doing will better represent the cellular complexity of the heart and how the processes of oxidate stress and telomere damage can lead to dysfunction.”
At a high level, Dr. Gurkar’s research project will investigate three primary aims:
- How oxidative telomere damage affects mitochondrial function and cellular aging
- How damage or stress affecting one type of heart cell may lead to dysfunction or changes in other cell populations, and
- The specific role that telomere repair may play in maintaining heart health.
“Our team includes an array of experts from the University of Pittsburgh and Carnegie Mellon University (including Tzahi Cohen Karni, PhD) in telomere biology, mitochondrial function, cellular aging, and heart tissue engineering,” says Dr. Gurkar. “We’re attempting to better understand how environmental factors that individuals are exposed to over their lifespan contributes to telomere damage and ultimately heart disease. Understanding these mechanisms could lead to new treatments and prevention strategies for one of the most prevalent conditions in the United States and around the world.”
Study Reference Link
Telomere Dysfunction Driven Molecular Outputs in the Cardiac Unit. Project Number: R01ES035733.
About Dr. Gurkar
Dr. Gurkar joined the division and Aging Institute in 2017. She is a prior recipient of an NIH K99/R00 Pathway to Independence grant from the National Institute on Aging. Before joining the University of Pittsburgh and the Aging Institute, Dr. Gurkar was a postdoctoral researcher at Massachusetts General Hospital/Harvard Medical School and Broad Institute of MIT and Harvard, and at the Scripps Research Institute in Florida. Dr. Gurkar earned her doctorate from Boston University School of Medicine.
Further Reading
The paper below from the Gurkar Laboratory was published in March 2024 and provides evidence for the molecular fingerprint of biological aging, uncovering blood-based biomarkers linked with healthy and rapid aging.
Other Recent Articles in the Press About Dr. Gurkar’s Research
