Event
BIOE Seminar: Biomechanics and Mechanobiology of Pulmonary Arterial Hypertension
Friday, May 10, 2024
9:00 a.m.-10:00 a.m.
A. James Clark Hall, Room #2121
Alisa Morss Clyne
aclyne@umd.edu
Daniela Valdez-Jasso
Associate Professor
University of California - San Diego
Biomechanics and Mechanobiology of Pulmonary Arterial Hypertension
Abstract
Pulmonary arterial hypertension (PAH) involves adverse remodeling of pulmonary arteries, more prevalent in women, leading to a <50% 5-year survival rate due to right-ventricular (RV) failure. Current therapies can't prevent RV failure or reverse vascular remodeling. Our multi-scale approach, from in-vivo physiology to molecular studies, identified significant sex differences in tissue remodeling in sugen-hypoxia rats. Extracellular matrix remodeling in large pulmonary arteries' adventitia emerged as a major contributor to hypertension. In-vitro and computational studies revealed greater mechano-signaling responses in female pulmonary arterial adventitial fibroblasts. Male rats rely on hypertrophy for compensated systolic function, while females recruit increased myocyte contractility and hypertrophy less. Male rats develop increased filling pressures and myocardial matrix stiffening, whereas females are protected from fibrotic remodeling. Isolated cardiac myocytes in females show higher functional reserve in calcium handling than males, and RV fibroblasts exhibit distinct mechano-signaling responses. These findings suggest a novel understanding of PAH pathophysiology, emphasizing crucial differences in mechanisms and outcomes between sexes.
Speaker Bio
Dr. Daniela Valdez-Jasso is an Associate Professor of Bioengineering at the University of California San Diego. She received her Bachelor’s degree in Applied Mathematics in 2005, her Master’s degree in Applied Mathematics in 2008, and her doctorate in Biomathematics in 2010, all at North Carolina State University. Her graduate thesis was recognized for its excellence with a Lucas Research Award. During her postdoctoral training at the University of Pittsburgh School of Medicine, she was an American Heart Association postdoctoral fellow, and a member of the Vascular Medicine Institute and the McGowan Institute for Regenerative Medicine.
In 2013, she was appointed as an Assistant Professor of Bioengineering at the University of Illinois at Chicago, where she established her research laboratory in biomechanics, mechanobiology and multi-scale mathematical modeling of the heart and lung in pulmonary arterial hypertension. In 2017, she was recruited to the Bioengineering Department at the University of California San Diego. Her work has been funded by the American Heart Association, a National Science Foundation CAREER award, a National Heart, Lung, and Blood Institute R01, and the Wu Tsai Foundation. Dr. Valdez-Jasso is a faculty member of two UC San Diego NIH training grants, has been nominated and awarded departmental and national honors, including the Fronek Family Lectureship and Shu-Chien Early Career Award. Her efforts as a mentor to lower barriers and expand participation in biomedical engineering of diverse and under-represented groups have been recognized by the Institute of Engineering in Medicine Gemini Faculty Award in 2022. Her contributions to the field of biomechanics and mechanobiology are now recognized with the Richard Skalak Chancellor's Endowed Faculty Fellowship in Biomedical Engineering.
