Biophysical and Biomolecular Interactions of Malaria-Infected Erythrocytes in Engineered Human Capillaries
This week we profile a recent publication in Science Advances from the laboratory of Dr. Ying Zheng (pictured, front row left) at UW.
Can you provide a brief overview of your lab’s current research focus?
The focus of the Zheng lab’s research is to understand and develop models for vascular growth and remodeling for different vascular beds. We are working on understanding organ-specific endothelial cell heterogeneity, developing organ-specific vascular structure, and exploiting different hemodynamic responses mimicking different vascular beds in vivo. We have several organs of interest, primarily heart, kidney, brain, as well as liver and lungs .
What is the significance of the findings in this publication?
We made a leap in generating microvessel models. We are able to generate robust 5-10 um capillaries with high fidelity and reproducibility. This is important for the community to be able to study small vascular diseases that is hardly possible to image in vivo, which has been a critical challenge in the engineering and vascular biology fields, in particular for microvascular occlusion in diseases such as malaria and sickle cell disease. It is known that capillaries in vivo are often blocked or obstructed in these diseases, which block blood flow to cause organ damage. There is no good understanding or effective treatment. One big barrier has been the inability to test new desquestration strategies in physiological in vitro models that faithfully mimic the microcirculation. Previous models have used narrow glass or plastic devices that lack key attributes of blood vessels. Our study made it possible to model the interactions of red blood cells with capillaries that mimic in vivo structures, and demonstrated the sequential role of biochemical and biophysical factors of infected RBCs in their sequestration and microvascular occlusion in the capillaries.
What are the next steps for this research?
We are working on developing organ-specific vascular beds with their unique structure, and apply the specific hemodynamics to fully mimic organ-appropriate vascular beds to model diseases and develop vascularized tissues for regeneration.
This work was funded by:
This work is supported by the National Institutes of Health (NIH) grant RO1 HL130488-01, and partially by R01HL141570, UG3TR002158 and UH2/UH3 DK107343.