Life Sciences Seminar: Role of long-non-coding-RNAs controlling vascular cell fate in response to genotoxic stress

Life Sciences Seminar
Role of long-non-coding-RNAs controlling vascular cell fate in response to genotoxic stress

Dr. Cristina Espinosa-Diez
Postdoctoral Associate at the Vascular Medicine Institute
University of Pittsburgh

Abstract:
Cancer survivors have an 80% risk of developing cardiovascular disease associated with radiotherapy, including major vascular events such as hypertension, atherosclerosis, thrombosis, and impaired vascular remodeling. Radiotherapy's off-target effects on the normal vasculature are caused by genotoxic stress and DNA damage accumulation. But how does radiation initiate the chronic response that leads to vascular events years after therapy? What is the role of vascular cells (endothelial and smooth muscle cells) in initiating cardiovascular disease associated with radiotherapy? Previous studies focused on understanding the significance of increased radiation-induced oxidative stress and inflammation. But they overlooked the potential of epigenetic changes – genome changes that do not alter the DNA sequence – leading to chronic cardiovascular disease. Epigenetic regulatory mechanisms involve different molecular processes, including DNA methylation, histone modifications, and long-non-coding-RNAs (lncRNAs). My work has established that radiation-induced-genotoxic stress leads to changes in epigenetic modifications, such as DNA methylation and differentially expressed lncRNAs in vascular cells. However, only a handful of lncRNAs have been functionally evaluated in vascular disease states, and the crosstalk between DNA methylation and lncRNAs is still unexplored. As an independent researcher, I propose a new approach to understanding how genotoxic stress influences epigenetic modifications and a platform to test lncRNAs as therapeutic targets to prevent chronic endothelial dysfunction.

Intended Audience:
Beginners, undergraduates, graduates. Those with interest in the topic.
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