Determining the effect of immune checkpoint blockade on macrophages against Lewis Lung Carcinoma

Description
Immunotherapy uses the body’s immune system to find and terminate cancerous cells, and has revolutionized cancer treatment. However, in certain cancers, such as lung cancer, less than 50% of patients respond to treatment. This is in part due to the

Immunotherapy uses the body’s immune system to find and terminate cancerous cells, and has revolutionized cancer treatment. However, in certain cancers, such as lung cancer, less than 50% of patients respond to treatment. This is in part due to the immunosuppressive tumor microenvironment, which is composed of factors that promote tumor growth and proliferation. Tumor cells create a highly immunosuppressive microenvironment by triggering the anti-inflammatory phenotype of myeloid immune cells, which largely consist of tumor-associated macrophages (TAMs). Anti-PD-1 and anti-PD-L1 immune checkpoint blockade therapy helps promote the T cell anti-tumor response by releasing the brakes on cytotoxic T-cells. However, it is unclear how TAMs respond to these immune checkpoint antibodies. Our lab hypothesizes that blockade of the PD-1/PD-L1 signaling pathway drives a pro-inflammatory macrophage phenotype. This hypothesis is supported by data generated in the B16F10 murine melanoma model, but it is unknown whether macrophage response to PD-L1 blockade is generalizable to other tumor contexts. Thus, the goal of the project is to determine the impact of immune checkpoint blockade on murine macrophages in the Lewis Lung Carcinoma (LLC) model. Using Flow Cytometry, macrophage phenotypes will be analyzed to confirm whether a pro- inflammatory or anti-tumor response is generated.
Date Created
2024-05
Agent

Investigating Immunomodulatory Properties of Trophoblasts on NK-92 Cells

Description

This study was conducted to determine how 3D cultured trophoblasts' secreted factors impact NK-92 activation and cytotoxicity during early pregnancy. In this study, 6 week gestational age human cytotrophoblast stem cells (iCTB) were cultured in 2D, 3D matrigel, and 3D

This study was conducted to determine how 3D cultured trophoblasts' secreted factors impact NK-92 activation and cytotoxicity during early pregnancy. In this study, 6 week gestational age human cytotrophoblast stem cells (iCTB) were cultured in 2D, 3D matrigel, and 3D synthetic hydrogels composed of 20 kDa 4-arm poly(ethylene glycol)-maleimide (PEG-Mal) modified with a GFOGR adhesive ligand (1 mM) and crosslinked with dithiothreitol (DTT), a non-degradable crosslinker. On day six, trophoblast supernatants were collected to investigate the influence of trophoblast organoid secreted factors on activated NK cell phenotype, measured by CD107a expression and levels of IFNγ secretion. Here we demonstrate that NK-92 cells possess a dNK2-like phenotype, and that supernatants of cytotrophoblasts cultured in 2D and synthetic hydrogels, but not matrigel, reduce activated NK-92 cytokine secretion.

Date Created
2023-05
Agent

Haug_PPT_Spring_2023.pdf

Description
Pelvic organ prolapse (POP) is a condition involving the weakening of the pelvic floor, with a prevalence of up to 50% of women experiencing the condition to some degree. Individuals with the condition are susceptible to multiple symptoms include vaginal

Pelvic organ prolapse (POP) is a condition involving the weakening of the pelvic floor, with a prevalence of up to 50% of women experiencing the condition to some degree. Individuals with the condition are susceptible to multiple symptoms include vaginal protrusion, dyspareunia, and difficulties with waste excretion. Risk factors are common and numerous for POP, and the economic burden of the condition poses a significant cost to nations worldwide. For many years, the primary solution to POP was the usage of transvaginal meshes, often composed of polypropylene, but rising reports of harmful side effects have led to their recall. Due to this, the space is open for novel solutions, and treatments based in regenerative medicine are on the rise. One such potential treatment is the usage of functionalized polyvinyl alcohol scaffolds to support the regeneration and strengthening of the pelvic floor. To validate the usage of this scaffold, this study focuses on the biocompatibility of the scaffolds, with specific focus on the maintenance of cell viability and proliferation on the scaffold. Through usage of metabolic assays and fluorescence microscopy, scaffolds composed of functional polyvinyl alcohol with cellulose have shown promise in supporting the cell types necessary for reconstructing the pelvic floor.
Date Created
2023-05
Agent

Haug_Spring_2023.pdf

Description
Pelvic organ prolapse (POP) is a condition involving the weakening of the pelvic floor, with a prevalence of up to 50% of women experiencing the condition to some degree. Individuals with the condition are susceptible to multiple symptoms include vaginal

Pelvic organ prolapse (POP) is a condition involving the weakening of the pelvic floor, with a prevalence of up to 50% of women experiencing the condition to some degree. Individuals with the condition are susceptible to multiple symptoms include vaginal protrusion, dyspareunia, and difficulties with waste excretion. Risk factors are common and numerous for POP, and the economic burden of the condition poses a significant cost to nations worldwide. For many years, the primary solution to POP was the usage of transvaginal meshes, often composed of polypropylene, but rising reports of harmful side effects have led to their recall. Due to this, the space is open for novel solutions, and treatments based in regenerative medicine are on the rise. One such potential treatment is the usage of functionalized polyvinyl alcohol scaffolds to support the regeneration and strengthening of the pelvic floor. To validate the usage of this scaffold, this study focuses on the biocompatibility of the scaffolds, with specific focus on the maintenance of cell viability and proliferation on the scaffold. Through usage of metabolic assays and fluorescence microscopy, scaffolds composed of functional polyvinyl alcohol with cellulose have shown promise in supporting the cell types necessary for reconstructing the pelvic floor.
Date Created
2023-05
Agent

Investigating Cellular Viability and Proliferation on 3D-printed Scaffolds for the Treatment of Pelvic Organ Prolapse

Description

Pelvic organ prolapse (POP) is a condition involving the weakening of the pelvic floor, with a prevalence of up to 50% of women experiencing the condition to some degree. Individuals with the condition are susceptible to multiple symptoms include vaginal

Pelvic organ prolapse (POP) is a condition involving the weakening of the pelvic floor, with a prevalence of up to 50% of women experiencing the condition to some degree. Individuals with the condition are susceptible to multiple symptoms include vaginal protrusion, dyspareunia, and difficulties with waste excretion. Risk factors are common and numerous for POP, and the economic burden of the condition poses a significant cost to nations worldwide. For many years, the primary solution to POP was the usage of transvaginal meshes, often composed of polypropylene, but rising reports of harmful side effects have led to their recall. Due to this, the space is open for novel solutions, and treatments based in regenerative medicine are on the rise. One such potential treatment is the usage of functionalized polyvinyl alcohol scaffolds to support the regeneration and strengthening of the pelvic floor. To validate the usage of this scaffold, this study focuses on the biocompatibility of the scaffolds, with specific focus on the maintenance of cell viability and proliferation on the scaffold. Through usage of metabolic assays and fluorescence microscopy, scaffolds composed of functional polyvinyl alcohol with cellulose have shown promise in supporting the cell types necessary for reconstructing the pelvic floor.

Date Created
2023-05
Agent

Age-associated changes to lymph node stromal cell maturation

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Description

In order to determine whether the spatial organization of FRCs and their expression of maturation markers (such as Ltbr) are altered with age, I performed immunofluorescence on frozen and cryosectioned whole lymph nodes from young and aged mice. My second

In order to determine whether the spatial organization of FRCs and their expression of maturation markers (such as Ltbr) are altered with age, I performed immunofluorescence on frozen and cryosectioned whole lymph nodes from young and aged mice. My second aim was to perform RT-qPCR and flow cytometry in order to determine whether FRCs from aged mice have altered expression of maturation markers when compared to young mice. Thus, the goal of the honors thesis research was to determine whether lymph node FRCs in the aged mouse exhibit signs of impaired maturation in their protein and gene expression. As the immune system is profoundly impacted by aging, my project supports a cellular mechanism by which defects in aged tissues disrupt immune cell function. Therefore, understanding the age-associated decline in host defense could provide new avenues for the treatment of many diseases of which the elderly are most vulnerable, in particular re-emerging and novel pathological agents such as COVID-19.

Date Created
2021-05
Agent