2022 Dr. Kitty Fronek and Dr. Arnost Fronek Lecture - Biomechanics and Mechanobiology of Pulmonary Arterial Hypertension

Daniela Valdez-Jasso, Ph.D.

Associate Professor

Bioengineering Department

University of California, San Diego

 

 


Seminar Information

Seminar Date
November 18, 2022 - 2:00 PM

Location
The FUNG Auditorium - PFBH

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Abstract

Pulmonary arterial hypertension (PAH) is caused by adverse idiopathic remodeling of the pulmonary arteries, is ~3X more prevalent in women, and results in 5-year survival ~50% due to right-ventricular (RV) failure. There are no therapies to prevent RV failure or reverse vascular remodeling in PAH. My lab uses multi-scale experimental and computational modeling approaches that spans from organ-scale in vivo physiology and hemodynamics to tissue-scale structural and mechanical analysis and molecular studies of cell mechano-signaling. In sugen-hypoxia rats, we showed for the first time that the progression of arterial and ventricular tissue remodeling differ significantly between in males and females. While many studies focus on smooth muscle cells in small pulmonary arteries, our new experiments and models showed that extracellular matrix (ECM) remodeling in the adventitia of large pulmonary arteries is a major contributor to decreased compliance and hypertension. In-vitro studies and computational models of mechano-signaling in pulmonary arterial adventitial fibroblasts showed that profibrotic signaling and gene expression in these cells are regulated by stretch and substrate stiffness and differ significantly between male and females.

In the heart, in-vivo measurements, and computational modeling show that while the male RV relies on hypertrophy to maintain compensated systolic function, female rats recruit increased myocyte contractility and hypertrophy less. While male rats developed increased filling pressures and profound myocardial matrix stiffening, female rats were protected from this fibrotic remodeling. In isolated cardiac myocytes, calcium handling was enhanced in females but not males, and RV fibroblasts show distinct mechano-signaling responses from left-ventricular cells. These experimental and computational results suggest a new paradigm in the pathophysiology of PAH and key differences in mechanisms and outcomes between males and females.

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.

In 2013, she was appointed as an Assistant Professor of Bioengineering at the University of Illinois at Chicago, and 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. She is the 2022 Shu Chien Early Career Lecture Awardee.

Dr. Valdez-Jasso has been an active mentor for minority students and an advocate for diversity

and inclusion at her campuses and for national professional societies. In 2020 she was the campus-wide recipient of the Faculty Inclusion Excellence Award at UC San Diego. She Chairs the Diversity and Inclusion Committee of the American Society of Mechanical Engineering Bioengineering Division, and in 2022, she was the recipient of the Galvanizing Engineering in Medicine Inclusion Initiative (GEMINI) Faculty Mentor awardee from the Institute of Engineering in Medicine at UC San Diego.