This is a slide deck with a brief description of Benjamin Gorman's 2020 SURF project. The below is the text of an abstract submitted along the results of this project to a North Carolina research symposium.
While antiretroviral therapy (ART) has dramatically reduced human immunodeficiency virus type 1 (HIV-1) mortality, ART cannot eliminate viral reservoirs in the brain and thus HIV-1 associated neurocognitive disorder (HAND) persists in 30-50% of patients. HIV-1 proteins, such as transactivator of transcription (Tat), have been shown to contribute to synaptodendritic injuries and inflammation correlated with HAND. One potential therapeutic target is the endogenous cannabinoid system.
Activation of cannabinoid receptors (CBR), which include CB1R, CB2R, and GPR18, have been shown to induce anti-inflammatory effects in various neurodegenerative disease models. CB2R and GPR18 are expressed on microglia, which are significant HIV reservoirs and have been implicated in HAND neuropathogenesis. These receptors are activated by a relatively novel monoacylglycerol lipase (MAGL) inhibitor through upregulation of the endocannabinoid 2-arachidonoylglycerol (2-AG). Despite potential clinical viability, the relationship between microglia, HAND, and CB2R and/or GPR18 signaling is not well understood.
To elucidate the microglia-mediated indirect effects of the Tat on neuronal function, the present study uses primary microglia and prefrontal cortex neuron culture models derived from postnatal day 1 and embryonic day 15–16 CD57/BL6 mice, respectively. Microglia cultures at DIV15 are treated with Tat, ABX1431, CB2R and GPR18 antagonists. Intracellular calcium levels, dendritic morphology, and neuronal injury are measured upon exposure to secretions of treated microglia, and microglial cytokine release is quantified. We hypothesize that Tat-exposed microglia will demonstrate increased production of various proinflammatory cytokines and induce dysregulation in neuronal health, with Abx1431 treatment attenuating these effects, possibly in a CB2R- or GPR18-dependent manner.
The Pecot Lab has discovered sequences for antisense oligonucleotides (ASOs) that can target the four most common mutations of KRAS (G12C, G12D, G12V, and G13D). We may utilize this sequence to synthesize an ASO that can effectively target mutated KRAS while sparing wild-type KRAS in healthy tissue to reduce potential toxic side-effects. Our project investigated the efficacy of EFTX-016 ASO to inhibit KRAS expression by investigating the cellular uptake and knockdown capability of our ASO sequences.
SURF Presentation - Daniel Pezzi - Eigenfucntions on Hyperbolic triangles
Creator:
Pezzi, Daniel
Date of publication:
August 28, 2020
Abstract Tesim:
Presentation for a Summer Undergraduate Research Fellowship project on Eigenfunctions on Hyperbolic triangles. Summarizes problem, results, and potential impact.
Determining whether intermittent energy restriction will reverse adverse effects of obesity and advanced age on breast cancer
Creator:
Craven, Dalton
Date of publication:
August 28, 2020
Abstract Tesim:
Advanced age and obesity are two major risk factors for breast cancer (BC). This presents a significant public health concern as the aging population and the incidence of obesity are increasing worldwide. Obesity-related acceleration of BC growth is explained, in part, through the development of a proinflammatory tumor-adjacent mammary adipose and an immunosuppressive tumor microenvironment. However, the mechanisms underlying age-related BC progression remain poorly understood. We have previously demonstrated in multiple mouse models of BC that, similar to obesity, advanced age accelerates tumor progression through systemic inflammation and tumor immune suppression. Given observed inflammation and tumor immunosuppression in aged and obese mice we seek to identify interventions that will reverse these adverse effects. Herein, the purpose of this project is to test our hypothesis that intermittent calorie restriction (ICR) will reverse the adverse effects of advanced age and/or obesity on tumor burden. These findings demonstrate that ICR decreases obesity and advanced age associated mammary tumor growth as well as systemic inflammatory markers that may contribute to tumor burden. Ongoing work is investigating whether ICR improves tumor immune surveillance.
Affiliation Label Tesim:
Gillings School of Global Public Health
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/st8z-wz72
Keyword:
Calorie restriction, Obesity , Breast cancer, and Aging
Language Label:
English
ORCID:
Other Affiliation:
Person:
Hursting, Stephen, Smith, Laura, and Craven, Dalton
Metaboendocrine and Inflammatory Correlates of Tumor Growth in a Mouse Model of Breast Cancer
Creator:
McFarlane, Tori
Date of publication:
August 28, 2020
Abstract Tesim:
This project sought to compare similar and different metaboendocrine and inflammatory markers in obese mice receiving either calorie restriction (dietary intervention) or gastric bypass (surgical intervention). The beneficial outcomes of these interventions were evaluated in the context of a murine model of breast cancer.
Determining Limitations of Deep Learning Super-Resolution
Creator:
Welborn, Zachary
Date of publication:
August 11, 2020
Abstract Tesim:
This project used Generative Adversarial Network implementations in MATLAB and Python to ultimately improve the resolution of simulated widefield microscope images. In both languages, a Pix2Pix implementation was used.
