Mechanics and Tissue Remodeling Integrating Computational and Experimental Systems (MATRICES)

National Institute Of Biomedical Imaging And Bioengineering, Bethesda

Investigators

Abstract

MATRICES lab has been purchasing equipment and supplies to setup our wet lab experimental space so that we can continue our research activities on sickle cell disease, proteolytic networks, and cancer metastasis. Due to collaborations we have made since arriving at NIH, we have been able to host two BETA Center Summer Interns that applied through the NIH SIP and have them work on two different projects under the guidance of Staff Scientist Hannah Song Lee and Lab Manager Russell Knutsen. Kingsley Garrett worked in collaboration with BEPS to develop a microfluidic artery comprised of fibrin gel matrix and seeded in the lumen with human aortic endothelial cells (HAECs). Fluorogenic gelatin was doped into the fibrin gel to provide a substrate susceptible to cleavage by proteases released from the HAECs that would serve as an indicator of activation. Since this fabricated artery would be used as an analog model to study the inflammation induced by sickle cell disease and its effects on activating proteolytic networks in endothelium, these cells were also stimulated with TNF-alpha or vehicle to quantify a difference in fluorescence between TNFalpha treated microfabricated vessels compared to vehicle controls. Jarrod Burns was another summer student who worked on determining the geometric differences between the internal carotid artery, middle cerebral artery, and anterior cerebral artery in mice homozygous for sickle cell disease (SS) or heterozygous for sickle cell disease (AS). Mice were obtained from our collaborator Dr. Fitzhugh and had their cerebrovasculature injected with Microfil to be imaged by micro computed tomography. Russell Knutsen completed these procedures, then Jarrods goal was to use the Analyze software to take geometric measurements of the main cerebral arteries implicated in humans for having increased blood velocities. Four mice from each genotype were prepared, imaged, and analyzed by Jarrod and Russ with more planned to be completed. These studies will be continued and expanded once our own mouse colony has been established and additional protocols for bone marrow transplantation, the only functional cure for sickle cell disease currently, has been approved.