Date(s) - 08/26/2019
3:00 pm - 4:00 pm
Anjelica Gonzalez, Ph.D.
Donna L. Dubinsky Associate Professor of Biomedical Engineering,
Yale School of Engineering and Applied Science
Engineering Human Microvasculature in Inflammatory and Fibrotic Disease
Microvascular dysfunction and disintegration is key to the genesis and progression of many diseases of capillary rich organs. Such organs include skin, kidney, heart and lungs, each abundant in microvasculature, and enriched in microvascular mural cells known as pericytes. The pericyte-elaborated basement membrane, while considered an important regulator of microvascular stability, has been inadequately characterized in the healthy, inflamed or fibrotic state. Further, in vivo systems have demonstrated that pericytes are capable of vascular destabilization and migration for the microvessel into the interstitial tissue during fibrosis, though mechanisms driving this activity have not been well elucidated.
Using engineered models of the composite microvasculature, in conjunction with engineered human lung and skin, we have explored the extent to which pericytes respond to proinflammatory and profibrotic signals, matrix protein composition, and signals generated by mechanotransduction in mechanically altered tissue. We have used such engineered models to determine the extent to which vascular and mural cells can contribute to leukocyte recruitment, vascular destabilization and tissue remodeling to progress and sustain a diseased microenvironment. Lastly, we have used such models in conjunction with human cells to determine the efficacy of currently approved and novel therapeutics to inhibit development, slow progression and potentially revers the matrix remodeling events facilitated by pericytes, fibroblasts and myofibroblasts in the skin and lung. Future transformation of our engineered system into high-throughput platforms will provide an excellent and efficient means of understanding the role of understudied cells, like pericytes, in disease initiation and progression. Similarly, the development of a high throughput platform will facilitate drug screening for orphaned or incompletely characterized drugs that would be effective in treating inflammatory and fibrotic disease.
Anjelica Gonzalez’ appointment as Associate Professor in the Department of Biomedical Engineering at Yale University has provided a platform for her research, focused on the development of biomaterials for use as investigational tools and therapeutic testing systems. Anjelica’s group focuses on the investigation of cellular and extracellular matrix contribution to microvascular immunoregulation and diseases that result from acute and chronic inflammation. Anjelica attended Utah State University, earning a B.S. in Irrigational and Biological Engineering and continued on to Baylor College of Medicine to pursue a PhD in Computational Biology.
Anjelica’s translational research interests have led to the development of new technologies that are being deployed in underserved and low-infrastructures settings across the world. PremieBreathe, a low-cost, mobile neonatal respiratory device invented by Anjelica, has been supported by the US Agency for International Development (USAID), Bill and Melinda Gates Foundation and NCIIA/Venturewell for development and deployment in Ethiopia.
Within Yale, Anjelica has been recognized for her dedication to exceptional teaching, having been awarded the Provost’s Teaching Award, the top prize awarded for teaching across all of Yale University, including Yale College, Yale School of Medicine, School of Management, and Yale Law School. Her efforts in education and public inclusion in science is noted by her opinion pieces published in Science and the New York Times.
To date, Anjelica’s research and social efforts have been acknowledged by national organizations, including the National Institutes of Health, NBC, Biomedical Engineering Society, Microcirculation Society, American Society for Investigative Pathology, the American Physiological Society and The Hartwell Foundation.