STAR Scholars Abstract

Socioeconomic Status, Perceived Control, and Inflammation Among Cancer Survivors

Background: Recent research suggests that perceived control, or the belief that one has control over one's life outcomes, may mediate the association between socioeconomic status (SES) and inflammation. However, little is known about whether this association persists among cancer survivors. The goals of this study were three-fold: 1) to examine SES differences in perceived control, 2) to test SES differences in inflammation, and 3) to examine differences in inflammation based on perceived control.  
Method: Data are from 298 cancer survivors (87.54% white; Mean age = 63.6) who participated in the Midlife in the United States (MIDUS) study wave 2 and Refresher. SES was measured by participant education, and the two markers of inflammation were interleukin-6 (IL-6) and c-reactive protein (CRP). Hypotheses were tested using a series of independent sample t-tests.
Results: Relative to those with bachelor's degrees, participants with lower education showed lower perceived control and elevated inflammation. Furthermore, lower perceived control was associated with elevated inflammation.
Discussion: Our findings provide early evidence that perceived control may mediate the association between SES and inflammation among cancer survivors.   

In 2023, the Centers for Disease Control and Prevention declared cancer as the second leading cause of death in the United States. Globally, liver cancer is deemed one of the most commonly diagnosed. Hepatitis B is a severe liver disease caused by a Hepatitis B virus (HBV) infection; a chronic HBV infection increases the likelihood of developing hepatocellular carcinoma (HCC), the most common form of liver cancer. Long noncoding RNAs (IncRNAs) are RNA transcripts classified by their greater than 200 nucleotide length and ack of protein-coding abilities. Although once believed to have no vital cellular function, they are now known to play critical roles in HCC development. We determined that IncRNA FAM99A is highly expressed in healthy hepatocytes but of negligible levels in liver cancer HepG2 cells and HCCs, thus hypothesized to function as a tumor suppressor. We used western blotting to assess expression of proteins that regulate apoptosis, such as Bax, Bcl-2, and cleaved caspase-3, when FAM99A was overexpressed in transformed liver cell lines, to determine if FAM99A affects apoptotic signaling pathways. A better understanding of FAM99A could provide further insight on HCC development and defining novel therapeutic targets.

Assessment of Neonatal Brachial Plexus Nerves Post Stretch Injury
Lindsay Hager1, Virginia Orozco1, Anita Singh2, Sriram Balasubramanian1 1Drexel University, Philadelphia, PA, 2Widener University, Chester, PA
Currently, only adult human and animal models exist for the understanding of brachial plexus morphology post stretch injury. The brachial plexus is a group of nerves around the shoulder, which when damaged can cause a loss of movement in the arm. The objective of this study was to assess neonatal piglet brachial plexus tissue for blood vessel and fiber disruption post stretch. Fifty-four H&E-stained slides from two piglets (3-5 days old) were imaged using a Leica DMI 4000 B microscope at 5x and 10x along the length of the nerve. Each image was scored by two independent observers using an adaptive scoring system. The observers were unaware of the extent of injury each nerve had previously undergone. By looking at the average scores per slide, it is evident that stretched nerves showed an increase in blood vessel rupture and fiber disruption than non-stretched nerves. This provides results exhibiting the structural changes of the brachial plexus nerves post stretch.  Conducting these experiments and analyzing the results can lead to a better understanding of the injury mechanism of neonatal brachial plexus palsy.

Title: Extent of Vascular Damage at Varying Degrees of Stretch in Hypoxic Neonatal Brachial Plexus

Abstract: In complex birthing scenarios, the brachial plexus (BP) nerves may be overstretched with additional complications of hypoxia. Characterizing extent of vascular damage in hypoxic neonatal BP at varying degrees of stretch can further our understanding of BP injury thresholds. All procedures were approved by Institutional Animal Care and Use Committee. Eleven neonatal piglets (3-5 days old) were anesthetized and exposed to FiO2 of 7% for 1 hour to induce hypoxia and re-perfused to FiO2 of 21%. BP nerves were exposed and stretched at a rate of 500 mm/min to predetermined low (<15%) and high (>15%) strains. Post-stretch, BP nerves were harvested and OCT-embedded. Ten-µm-thick serial longitudinal sections were stained with Hematoxylin-Eosin. Using Olympus BX53 motorized microscope, stained slides were imaged at 10x magnification along nerve length. Using a custom MATLAB script, each stitched image was split into regions of interest (ROI). An independent-blinded observer scored each ROI for vascular damage on a scale of 0-2 (0-no damage, 1-torn vessel, 2-scattered blood cells). Preliminary results show vascular damage increases with increasing stretch and similar degrees of damage were observed in central and peripheral regions. 

Title: Invisible threads in the cosmic tapestry: A study on neutrinos with the Deep Underground Neutrino Experiment 

Abstract: Neutrinos are invisible elementary particles that travel nearly at the speed of light, filling our surroundings at all times. These particles possess intriguing quantum properties and hold the distinction of being the most abundant particles with mass in the universe, playing a foundational role in cosmic processes. The Deep Underground Neutrino Experiment (DUNE) holds the key to understanding the fundamental properties of neutrinos. Operating within the Long-Baseline Neutrino Facility, DUNE employs a high-intensity neutrino beam created by a proton accelerator. After protons collide with a target, the resulting charged particles are directed into a decay pipe to decay into muons and muon neutrinos. The muon beam, which is much easier to measure than the neutrino beam, passes through three muon alcoves. This poster presentation focuses on quantifying and investigating the flux and energy of the muon beam through simulations and data analysis, making contributions to the DUNE mission. Through this analysis, we aim to deepen our understanding of neutrinos and advance our comprehension of the universe.

Decoding LLMs: Unveiling ChatGPT's Human-Like Deception
Generative artificial intelligence (AI) has revolutionized human-AI interactions, but ethical and societal concerns arise due to deceptive AI-generated content. Our research delves into the layers of deception in Large Language Models (LLMs) like ChatGPT, exploring their ability to produce texts without factual basis and the self-deception they trigger in users. Recognizing demographic biases in deceptive word choices through literature review, our study aims to answer whether AI mimics human deception. Having synthesized false human reviews for restaurants, hotels, and doctors, we curate a dataset of over 1000 personas using ChatGPT-generated names reflecting U.S. Census demographics. Furthermore, we test and fine-tune various prompts for ChatGPT to attain human-level deception. After generating reviews for each persona via ChatGPT, we utilize machine learning and NLP techniques to analyze and extract various linguistic biases that can be leveraged for AI-generated content detection. Ultimately, our goal is to gain insights into AI’s deception and its implications and refine methods for deception detection. Following STAR, I intend to continue research with my faculty mentor as we investigate diverse contexts and more LLMs.

The treatment of children with heart failure is a formidable challenge. Heart transplantation, when available, becomes the only lifesaving option. Children could benefit from a blood pump: a medical device designed to assist the ailing heart with pumping blood. Blood pumps for children, however, lag behind those for adults. While adult devices have been employed in children, the operation of these adult pumps off-design increases the risk of blood cell damage and clotting. Pediatric patients have limited options due to the anatomy of childhood heart disease and increased cardiovascular demands of physical growth. To address this unmet clinical need, we have innovated The Dragon Heart, which uniquely integrates multiple pediatric blood pumps. This compact device (60mm x 50mm) suspends the pumps in a magnetic field, thus facilitating a long operational lifespan and lower blood cell trauma. We performed high-quality modeling of two new pump designs, which produced target performance; 40-180 mmHg for 0.5-4 L/min at 2000- 3000 RPM. Internal fluid forces were below 2.5 N, and fluid stresses were at acceptable levels. This work serves as the foundation for the next phase of prototype benchtop testing, moving toward animal studies.

Nanoparticles have been used in various biomedical applications including drug delivery. Particle size influences critical factors such as cellular uptake and drug release. However, the current laboratory protocol for poly(lactic-co-glycolic acid) (PLGA) particle synthesis yields a broad particle size distribution, leading to inconsistent results. Here we developed a protocol to isolate particles of various sizes and assessed the relation between particle size and its drug release kinetics. Particles were synthesized using the double emulsion method and separated by size via centrifugation. Using Dynamic Light Scattering (DLS), we verified that particles were separated into 50 nm increments using the newly developed method. Preliminary data show that smaller particles display a higher drug release at early timepoints than larger particles. In addition, we also observed that same-size particles with higher Molecular Weight (MW) exhibit a slower drug release. These findings improve particle synthesis and expand our ability to tune particle properties. We are currently investigating the effect of particle size, and therefore drug release kinetics, in macrophage phenotype using Drug 1, a potent anti-inflammatory drug as the cargo.

2023 STAR Scholar

Title: Identification of novel ACSS2 inhibitors in regulating breast cancer brain metastatic growth

Triple negative breast cancer is an aggressive cancer with an overall survival rate of months when it spreads to the brain. There is no effective drug treatment for brain metastasis patients, thus novel therapies are urgently needed. Breast cancer cells that metastasize to the brain are dependent on fatty acids for growth. The acetyl CoA synthetase 2 (ACSS2) enzyme converts acetate to acetyl CoA, which is critical for the fatty acid production in tumors in the brain. The Reginato lab previously showed that genetically targeting ACSS2 can reduce the growth of breast cancer brain metastasis (BCBM) cells and identified novel ACSS2 inhibitors that show promise using in vivo models of breast cancer brain metastasis. Here, we show that treating BCBM cells with new second generation ACSS2 inhibitors 2749, 7033, and 4855 was able to block BCBM growth in crystal violet assays. Using western blotting, we show that novel ACSS2 inhibitors like 4855 lead to a reduction in E2F1: a downstream protein of the ACSS2. These results identify ACSS2 inhibitor 4855 as a potent inhibitor of BCBM cell growth and supports further testing of these novel ACSS2 inhibitors as novel therapeutic agents for the treatment of breast cancer brain metastatic growth.

STAR 2021 Scholar 

Title: Uncovering motor circuits involved in sensorimotor transformations using novel electron microscopy analysis tools

Sensorimotor transformation is the process by which sensory stimulus is converted to motor response. This is essential for survival as they lead to behaviors. We know less about how motor codes are relayed to motor circuits that drive a behavior because we do not know the connectivity of circuits within the spinal cord. We overcome this limitation by investigating sensorimotor connections within the fruit fly D. melanogaster, using a complete electron microscopy (EM) dataset of the ventral nerve cord (VNC, fly "spinal cord"). The VNC is accessible in insects because there is no vertebra, and their small size allows them to be a great model for human behavior. We first examine and compare new toolkits including Fly Wire, NeuPrint, and CATMAID that can be used to analyze EM data. We apply these tools to map out key neural connections within sensorimotor circuits that drive well-defined behaviors. We identify interneurons and motorneurons postsynaptic to descending neurons that are hypothesized to drive escape behaviors, like the Giant Fiber. Tracing the connectivity of these descending neurons gives insight into the specifics of fly behaviors and provides a better understanding of how sensorimotor circuits control motor output.