Future Faculty Career Exploration Program Seminar: A "lnc" between endothelial cell fate & genotoxic stress
Future Faculty Career Exploration Program
A "lnc" between endothelial cell fate & genotoxic stress
Dr. Cristina Espinosa-Diez
Gomez Lab, Department of Medicine, Division of Cardiology
Heart, Lung, and Blood Vascular Medicine Institute
University of Pittsburgh
Dr. Espinosa will be discussing her work looking at Radiotherapy and its impact on cancer patients. Specifically, looking at the increased risk of cardiovascular disease after radiotherapy. She will discuss her work with Epigentic modfications and discuss her findings during the presentation.
Radiotherapy is used in more than 50% of cancer patients. Since therapeutic improvements have led to extended cancer patients' survival, new research focuses on the chronic effects of radiation on normal tissue. Cancer survivors have up to an 80% risk of developing a cardiovascular disease related to radiotherapy, including major vascular events such as atherosclerosis, thrombosis, hypertension, and peripheral artery disease (PAD). But how does radiation initiate the chronic response that leads to vascular events years later? Studies have focused on understanding the significance of increased radiation-induced oxidative stress and inflammation, overseeing the potential of epigenetic changes leading to chronic vascular toxicity. Epigenetic modifications are heritable genome changes without altering the DNA sequence, including DNA methylation, histone modifications, and non-coding-RNAs (ncRNAs). Long-non-coding-RNAs (lncRNAs) are a subtype of ncRNAs that work as epigenetic modifiers and control gene expression. LncRNAs are essential for vascular adaptation to radiotherapy, and several studies, including ours, have identified a functional role for lncRNAs in vascular disease. However, only a handful of lncRNAs has been functionally evaluated in response to radiotherapy over different vascular disease stages. My work has established that radiation leads to the induction of different ncRNA from the DLK1-DIO3 cluster, including the lncRNA MEG9. We observed that MEG9 loss-of-function decreased cell proliferation and correlated with an increase in caspase-3-dependent cell death. Furthermore, MEG9 inhibition diminished sprouting angiogenesis while increased vascular permeability in vitro. To further understand the functional role of MEG9 in the vascular endothelium, we performed an endothelial-specific gene array, followed by gene ontology analysis. These results suggested that the most affected genes after MEG9 loss-of-function were involved in blood coagulation and thrombosis. Indeed, we confirmed that MEG9 inhibition in HUVECs promotes fibrin formation in human plasma. My work illustrates how epigenetic changes on specific ncRNA loci may affect the long-term cardiovascular function after exposure to genotoxic stressors such as radiotherapy. Our data suggested that the lncRNA MEG9 could have a potential protective role on maladaptive responses to genotoxic stress and that DNA methylation may be a mechanism to modulate vascular injury in response to stressors. As an independent researcher, I propose a new perspective to define lncRNA's importance in response to radiotherapy and their contribution to chronic vascular toxicity.
Cristina is a 5th year Postdoctoral Associate at the Vascular Medicine Institute. She obtained her Ph.D. (2015) in Molecular Biology and Biochemistry in the “Universidad Complutense” in Madrid, Spain and she did a previous postdoc at OHSU in Portland, OR. Cristina is passionate about non-coding-RNAs and she is currently focused on how small and long-non-coding-RNAs influence vascular cell identity in response to stress. Cristina recently relocated to Pittsburgh to work on the Gomez lab to study the crosstalk of different epigenetic mechanisms (histone modifications, DNA methylation, and non-coding-RNAs) in vascular smooth muscle cells. Before moving to Pittsburgh, Cristina was a board member of the OHSU Postdoc Association and she is currently involved with ECUSA (Spanish Scientist in the USA) enhancing the visibility of early-career scientists
Beginners, undergraduates, graduates. Those with interest in the topic.
This event is co-sponsored by The Office of Faculty Diversity and Recruitment
To request an interpreter, please visit https://myaccess.rit.edu
When and Where
Open to the Public