My lab will engineer in vitro disease models to study how both beneficial and pathogenic microorganisms interact with the ECM to initiate pathological behavior in the human host. My diverse training in tissue engineering and the gut microbiome uniquely qualify me to achieve this goal. Read about my current and past work below.
ENGINEERING DISEASE MODELS TO UNDERSTAND THE SEQUENCE OF EVENTS IN EARLY AORTIC VALVE DISEASE
During my Ph.D. in Prof. Kristyn Masters' lab, I designed in vitro models that mimicked the features of the ECM in early calcific aortic valve disease, an illness for which there is currently no treatment other than total valve replacement. Specifically, I sought to capture the glycosaminoglycan enrichment I had previously observed in a swine model of early valve disease through complementary bottom-up (biomaterials) and top-down (gene delivery) approaches. Using these models, I was able to identify a previously unknown cascade of pathological events.
Aortic valves in ex vivo culture enriched for hyaluronic acid (brown staining) at day 0 (left) versus day 7 (right).
EXPLORING THE EFFECT OF GEOGRAPHIC DIFFERENCES IN GUT MICROBIOTA ON SUSCEPTIBILITY TO INFECTION
For my postdoctoral training in Dr. Ilana Brito's lab, I am studying the gut microbiome in a global context. Most microbiome studies have been based on populations in the Global North even though the human microbiome is known to vary dramatically across the world. The extent to which these population-level variations contribute to host health is unknown. Using germ-free mouse models, I am evaluating the impact of microbiota composition among populations in high- versus low-income countries on susceptibility to infection. I have identified geographic differences in resistance to infections regulated by the Th17 mucosal immune pathway.
Colons (H&E stained) from mice humanized with human stool. The mouse on the left was resistant to the infection, while the one on the right was more susceptible.
UNRAVELING THE INTERACTIONS BETWEEN THE GUT MICROBIOME AND THE EXTRACELLULAR MATRIX IN INFLAMMATORY BOWEL DISEASE
With the support of a Cornell Presidential Postdoctoral Fellowship, I am engineering in vitro platforms to study the interplay between commensal bacteria and human gut ECM in the context of IBD. I have determined that many members of the “healthy” gut microbiome secrete enzymes that degrade multiple ECM components. I am currently designing biomaterials-based culture platforms to explore the impact of these bacterial modifications of the matrix on macrophage and fibroblast activation. My research program will continue to build on this work studying the interactions between microorganisms and human ECM that lead to pathological outcomes.
Culturing gut microbes in the anaerobic chamber.
The Internationalization of Gut Microbiome Research
Porras AM, Brito IL. The Internationalization of Gut Microbiome Research. Current Opinion in Microbiology, 50:50-55, 2019.
Creation of Disease-Inspired Biomaterial Environments to Mimic Pathological Events in Early Calcific Aortic Valve Disease
Porras AM, Westlund JA, Evans AD, Masters KS. Proceedings of the National Academy of Sciences of the United States of America, 115(3):E363-E371, 2018.
Robust Generation of Quiescent Porcine Valvular Interstitial Cell Cultures
Porras AM*, Engeland N*, Marchbanks E, McCormack A, Bouten C, Yacoub MH, Latif N, Masters KS. JAHA: Journal of the American Heart Association, 6(3):e005401, 2017. *Denotes equal contribution by authors
Calcific Aortic Valve Disease: A Battle of the Sexes
Porras AM, McCoy CM, Masters KS. Circulation Research, 120(4):604-606, 2017.
Engineering Approaches to Study Fibrosis in 3-D in Vitro Systems
Porras AM*, Hutson HN*, Berger AJ, Masters KS. Current Opinions in Biotechnology, 40:24-30, 2016. *Denotes equal contribution by authors.
Development of Aortic Valve Disease in Familial Hypercholesterolemic Swine: Implications for Elucidating Disease Etiology
Porras AM, Shanmuganayagam D, Meudt JJ, Kreuger CG, Rahko PS, Reed JD, Masters KS. JAHA: Journal of the American Heart Association, 4(10):e002254, 2015.
Wave Mice: a New Tool in the Quest to Characterize Aortic Valvular Disease Etiologies
Porras AM, Masters KS. Journal of Thoracic Disease, 7(9):E332-334, 2015.
Gene Expression Profiling of Valvular Interstitial Cells in Rapacz Familial Hypercholesterolemic Swine
Porras AM, Shanmuganayagam D, Meudt JJ, Krueger CG, Reed JD, Masters KS. Genomics Data, 1(2):261-263, 2014.
Manipulation of Valve Composition to Elucidate the Role of Collagen in Aortic Valve Calcification
Rodriguez KJ, Piechura LM, Porras AM, Masters KS. BMC Cardiovascular Disorders, 14(29), 2014.