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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Micro-Physiological Systems Seminar
Date and Time: November 12, 4:00 to 5:00 pm
BlueJeans link: http://bluejeans.com/283259977/8540
Hannah Viola
Title: Developing a functional assay of neutrophil recruitment and activation for immunomodulatory drug screening
Abstract: Neutrophil-driven pulmonary inflammation drives tissue damage in COVID-19, cystic fibrosis, acute respiratory distress syndrome, and many other life threatening diseases. High numbers of neutrophils crowd the lower lungs where they over-produce inflammatory cytokines and tissue-damaging proteases, Dnases, and neutrophil extracellular traps. This neutrophilic damage can't be controlled with current therapeutics, largely because patients with the same disease have widely different inflammation patterns that can't be controlled with the same drugs for each patient. Therefore, there is an urgent need to identify which patients require which drugs to target neutrophilic inflammation. To do this, animal models are inadequate because they cannot replicate patient-specific physiology and inflammatory patterns. Therefore, we developed a cell-based in vitro assay for testing neutrophil-targeted therapeutics. The assay is designed to study patient-specific differences in response to drugs that target neutrophil infiltration and activation in the deep lungs. The assay consists of the two cell types critical to the air-blood barrier: lung tissue epithelial cells and capillary endothelial cells. These two cell types are modeled with NCI-H441 epithelial cells on a membrane, sandwiched opposite a layer of human umbilical vein endothelial cells. Primary blood-derived neutrophils are placed on the endothelial cell layer, where they migrate through both the endothelium and epithelium into patient-derived lung fluids called tracheal aspirate. This patient-specific fluid programs neutrophils towards an activated state similar to how they behave in the patient. Therefore, our assay is suited to study patient-specific neutrophil programming and drug responses.
Camila Camargo
Title: Adhesion analysis for enrichment of CD8+ T cells with enhanced tumor homing capability for adoptive cell therapy
Abstract: Adoptive cell therapy (ACT) has emerged as a powerful treatment option for patients with metastatic melanoma. Despite encouraging results with this treatment modality, responses are seen in only a minority of patients. It is now known that low patient rates of response are due to poor tumor-infiltrating lymphocytes (TIL) survival post transfer as well as poor trafficking of transferred cells to relevant tissues. In order for TILs to infiltrate disease tissue from the blood vasculature, they utilize a highly orchestrated adhesion cascade that begins with selectin-mediated rolling adhesion to endothelial cells, followed by integrin mediated firm adhesion and subsequent extravasation. These adhesion ligand-receptor interactions have been implicated in TIL homing, however, an outstanding problem in the field is a lack of understanding how TIL’s surface adhesion ligands initiate and sustain adhesion interactions with the tumor vasculature, and how this may lead to improved engraftment of TILs to the tumor microenvironment. As such, the overall objective of this my work is to utilize engineered microfluidic devices that enable the interrogation of adhesive behavior of cells under relevant hemodynamic forces to 1) determine what adhesion receptors, cytokines, and activation markers are present in highly adhesive cells and 2) how in vitro adhesion predicts in vivo homing. This work will provide insight into which TIL’s subpopulation is the most appropriate for enhanced tumor homing for ACT.
