Biochemical Phenomena, Metabolism, and Nutrition Commons^™

Kras-Independent Factors Drive Pi3k Signaling And Circumvent The Necessity Of Kras-Driven Pi3k Activation In Pdac, Lucas Christopher Bialousow

MUSC Theses and Dissertations

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest five-year survival rates among cancers and is characterized by near-ubiquitous occurrence of oncogenic KRAS mutations. Oncogenic KRAS activates several downstream pathways, including ERK 1/2 MAPK and PI3K, which are critical for PDAC. However, accumulating evidence suggests that PI3K activity can be maintained independent of oncogenic KRAS. The high prevalence of KRAS^G12R in PDAC challenges the prevailing model of KRAS-driven PI3K activation, as this mutant is defective in direct engagement with PI3Kα. These observations raise important questions regarding how PI3K signaling is sustained in PDAC. Here, we investigated KRAS-independent mechanisms that …

Titanium Dioxide: An Inquiry Into The Mechanisms And Implications Of Exposure In Gut Dysbiosis And Metabolic Disorders, Meghan Gardiner

Senior Honors Theses

Titanium dioxide (TiO₂) is one of the most prevalent food additives utilized in commercial products in the United States. While TiO₂ was originally hailed as a nontoxic and cost-effective additive, studies are beginning to reveal that TiO₂ is not as safe as it once seemed. TiO₂ may contribute to the development of insulin resistance and metabolic disorders through direct and indirect mechanisms. The compound induces gut dysbiosis, leading to alterations in bacterial metabolites and pro-inflammatory cytokines, which results in the selective resistance of glucocorticoid receptors. Additionally, TiO₂ itself can translocate from the gut to …

Impaired Mitochondrial Magnesium Transport Induces Genome-Wide Transcriptional Changes In Hepatic Steatosis, Inflammatory Signaling, And Detoxification Pathways During High-Fat Diet Feeding, Abhishek Shastry, Thiruvelselvan Ponnusamy, Asha Parveen Sakkarai Mohamed, Marianne Assogba, Natarajaseenivasan Kalimuthusamy, Shanmughapriya Santhanam

Rowan-Virtua Research Day

Calcium overload during fatty diet consumption induces oxidative stress and mitochondrial apoptosis. Intramitochondrial magnesium inhibits calcium uptake into mitochondria; therefore, modulating the activity of the mitochondrial magnesium transporter Mrs2 may regulate calcium-induced hepatocellular stress. As previous work demonstrates that liver-specific Mrs2 inhibition increases hepatic lipid deposition, RNA-sequencing was performed to identify potential transcriptional mechanisms for hepatocellular stress.

Mrs2 knockout (Mrs2^KO) mice were generated by crossing male Mrs2^fl/fl mice with liver-specific-Cre transgenic mice. Eight-week-old wild-type (Mrs2^WT) and Mrs2^KO mice were placed on chow or high-fat diet (HFD) for 12 months (n=3/group). Whole liver was collected …

Mechanistic Insights Into Enterolactone-Mediated Glut4-Dependent Glucose Uptake, Merritt Smith

Senior Honors Theses

Type 2 diabetes mellitus (T2D) is one of the leading causes of morbidity and mortality in the United States, with approximately 25% of healthcare expenditures directed toward its management and associated metabolic complications. In response to the urgent need for novel therapeutic strategies, recent research has focused on bioactive compounds derived from dietary sources. In light of that, we identified the plant lignan matairesinol (MA) and its gut-derived metabolite, enterolactone (ENL), as agents capable of enhancing glucose uptake in 3T3-L1 differentiated adipocytes. These results suggest that enterolactone may represent a promising dietary supplement for improving glycemic control in patients with …

Investigating Sertraline‑Mediated Modulation Of Succinate Dehydrogenase To Sensitize Tmz‑Resistant Glioblastoma Cells, Supraja Mallapuram

Create@State

Glioblastoma (GBM) is one of the deadliest and most common brain tumor which remains highly resistant to temozolomide (TMZ), contributing to poor patient outcomes. Literature suggests that sertraline, a widely used SSRI, disrupts mitochondrial metabolism in cancer cells. Because GBM depends heavily on succinate dehydrogenase (SDH) for oxidative phosphorylation, sertraline‑mediated SDH inhibition may increase metabolic stress and reduce functional TMZ resistance. This poster presents a literature‑based rationale and proposed experimental design to evaluate sertraline‑induced SDH modulation and its potential to sensitize TMZ‑resistant T98G glioblastoma cells. These findings will guide future experimental work.

Organic Synthesis Of A Hydrazine Functionalized Ammonium Compound For Improved Capture Of Aldehyde Metabolites From Exhaled Breath, Po'iu N. Burgo

Undergraduate Theses

Breath analysis has emerged as a non-invasive and inexpensive way to screen for respiratory diseases. This technique involves measuring concentrations of specific metabolites found in exhaled breath that serve as a biomarkers for disease. A subclass of volatile organic compounds called α,β-Unsaturated aldehydes, products of the lipid peroxidation mechanism, are underrepresented as biomarkers of lung cancer. These have been found to have relatively increased concentrations in the exhaled breath of lung cancer patients compared to a healthy patient. One of the reasons that these metabolites have been underreported is that the techniques used to measure and characterized exhaled metabolites do …

The Role Of The "Indulgent Mindset" As A Modulator For Neuropsychiatric Biomarkers And Self-Reported Mental Wellbeing, Riva Ranier, Anika Anika, Sarah Simon, Ethan Chau, Emma Monte, Madison Retzloff, Johann Luna, Susan Helm

Seaver College Research And Scholarly Achievement Symposium

The Role of the "Indulgent Mindset" as a Modulator for Neuropsychiatric Biomarkers and Self-Reported Mental Wellbeing

Objective: Limited understanding persists regarding how an "indulgent mindset" about food shapes neuropsychiatric outcomes. Building on the "milkshake study" demonstrating that mindset modulates ghrelin response independent of nutritional content, this pilot study examines whether an indulgent mindset intervention affects neuropsychiatric biomarkers and mental wellbeing.

Methods: Women ages 19-65 (n=35; intervention n=17, control n=18) completed a 6-month randomized trial with baseline and post-intervention assessments including 3-day food diaries, mental wellbeing questionnaires, and comprehensive metabolomics (Iollo panel across mental health, metabolic health, gut microbiome, brain health, …

Atp Architect - Development Of A Metabolism Boardgame, Selene J. Welch, Micah Burk, Brooklyn Gilchrist, Emma Haase, Timothy T. Jones

SACAD: Scholarly Activities

Traditional metabolism instruction often leaves students struggling with pathway interconnectedness and metabolite flux. To foster systems thinking, we are developing an educational board game where students manipulate tokens to navigate physiological constraints and achieve target energy goals. Grounded in Design-Based Research (DBR), the game undergoes iterative refinement based on player feedback. The design utilizes constructivism by allowing students to "fail safely" and revise strategies in real-time, while leveraging embodied cognition to externalize abstract flux into the physical trading of resource tokens.

A Ubiquitin Code Written In Circadian Time: Evaluating Protein Linkages In A Drosophila Model, Alejandro Damian, Elinor Harrison, Cj Dalton

Medical Student Research Symposium

Background: Ubiquitin is a small polypeptide that serves many functions within a cell, including modifying proteins, marking them for degradation through the ubiquitin-proteasome system (UPS). Circadian rhythms regulate many cellular processes, but its role on the individual linkages of ubiquitin is poorly understood. This project aims to determine whether there is a circadian pattern for the conjugation of ubiquitin. Methods: Wild-type (Oregon R) Drosophila were entrained to a circadian cycle with standard light and dark environments. The whole heads were then frozen and removed at different times and used to quantify protein linkages using western blotting and antibodies to each …

The Effects Of Body Mass Index On Fertility And In Vitro Fertilization, Morgan R. Kidd

Honors College Theses

In-vitro fertilization (IVF) is the most widely used type of assisted reproductive technology for treating infertility arising from a number of conditions. As obesity rates continue to climb in the United States, infertility has been discovered to have a direct correlation. Individuals that fall below or above the healthy body mass index range are found to have disrupted regulation of the hypothalamic-pituitary-gonadal axis, resulting in diminished reproductive health. Those that are diagnosed as infertile due to conditions caused by the effects of low body mass index or high body mass index may seek assisted reproductive technologies to intervene in achieving …

Weaning Drives Microbiome-Mediated Epigenetic Regulation To Shape Immune Memory In Mice, Li Yang, Robert C Peery, Shirui Zhou, Xiaomin Chen, Leah M Farmer, Fabiola Gutierrez, Stephanie Fowler, Lanjing Zhang, Julia M Salamat, Karen Riggins, Jiejun Shi, Lanlan Shen

Children’s Nutrition Research Center Staff Publications

During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, …

3'Utr Mapping Reveals Alternative Polyadenylation In Right Ventricular Failure, Rahul Neupane, Kartiga Natarajan, Erik E Suarez, Henry J Pownall, Kai-Lieh Huang, Eric J Wagner, Ajay Kumar Verma, Rambabu Majji, Hari Krishna Yalamanchili, Ashrith Guha, Rajarajan A Thandavarayan

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Misregulated Alternative Splicing In Endometriosis: A Role For Aberrant Mrna Variants In Endometriotic Cell Growth, Venkata Naga Goutham Davuluri, Michelle Dias, Roxanna Llinas, Kamath Neha, Pooja Popli, Shannon M Hawkins, Chandrakant Tayade, Elise T Courtois, Hari Krishna Yalamanchili, Ramakrishna Kommagani

Children’s Nutrition Research Center Staff Publications

Endometriosis is a chronic gynecological disorder marked by the growth of endometrial-like tissue outside the uterus, often leading to pelvic pain, inflammation, and infertility. Despite its global prevalence, diagnosis remains delayed, and effective non-surgical treatments are lacking. While recent transcriptomic studies have identified mRNA transcript changes in ectopic lesions, the contribution of alternative pre-mRNA splicing, a key posttranscriptional regulatory layer, remains largely unknown. In this study, we performed a comprehensive analysis of alternative splicing (AS) events in endometriotic lesions using transcriptomic data. We uncovered distinct alterations in alternative splicing events are associated with endometriosis, highlighting a previously underappreciated layer of …

Investigating Corollaries Between Streptococcus Gallolyticus Subsp. Gallolyticus Virulence And Colorectal Cancer, Tyler G. Myers

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Streptococcus gallolyticus subsp. gallolyticus (Sgg) is a gram-positive, non-beta-hemolytic bacterium that belongs to the Lancefield group D of streptococcal pathogens. For the past several decades, associations between Sgg bacteremia and colorectal cancer (CRC) have been apparent, with gastroenterologists routinely recommending colonoscopies for positive cases of Sgg in either blood or stool samples. However, current research has not wholly established whether Sgg acts as a causative agent of CRC or if pre-existing cancers make the lumen of the colon more hospitable to its colonization. Regardless, Sgg has been implicated in the modulation of host inflammatory pathways and subsequent remodeling …

Inverse Associations Of Serum Total Omega-6 Polyunsaturated Fatty Acids And Linoleic Acid With Biomarkers Of Inflammation: A Cross-Sectional Analysis, Kevin C Maki, Xiwei Chen, Meredith L Wilcox, Carol F Kirkpatrick, Liana L Guarneiri, Orsolya M Palacios, Erika T Beidelman, Anna Lm Macagno, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Observational evidence supports associations between higher consumption of omega-6 (n-6) polyunsaturated fatty acids (PUFAs) with reduced risks for cardiometabolic diseases. However, some have hypothesized that higher n-6 PUFA intake may be proinflammatory.

Objectives: The purpose of this cross-sectional analysis using baseline data from the Aegis cohort was to examine associations of serum total n-6 PUFA and linoleic acid concentrations with biomarkers of inflammation.

Methods: Serum concentrations of high-sensitivity C-reactive protein (hs-CRP), glycoprotein acetyls, serum amyloid A (SAA), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were assessed as biomarkers of inflammation. Univariate Pearson correlation coefficients …

A Case Of Autosomal Dominant Polycystic Kidney Disease With Multiple Bilateral Spontaneous Retroperitoneal Hemorrhages, Masato Mizuta, Tatsuya Suwabe, Yuki Oba, Akinari Sekine, Masayuki Yamanouchi, Hiroki Mizuno, Eiko Hasegawa, Takehiko Wada, Makoto Fukuda, Motoaki Miyazono, Naoki Sawa, Yoshifumi Ubara

Children’s Nutrition Research Center Staff Publications

We experienced a 45-year-old male with ADPKD who developed spontaneous retroperitoneal hemorrhages with hypertension in the right subcapsular renal space without trauma. After his condition worsened with conservative management, he was treated by renal transarterial embolization (TAE). Over the next eight years, he experienced bilateral bleeding at three different sites and underwent repeated endovascular treatment with renal TAE to stop the bleeding. After the fourth occurrence, the patient underwent hemodialysis. Although renal cysts and urinary tract bleeding occur frequently in ADPKD, retroperitoneal hemorrhage is rare; however, TAE is both effective and a good way to preserve renal function.

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …

Perceptions And Use Of Behaviour Change Interventions For Physical Activity In Chronic Respiratory Disease In The Republic Of Ireland, Ciara Hanrahan, Joseph G Mcveigh, Terence M O'Connor, Thierry Troosters, Julie Broderick

Children’s Nutrition Research Center Staff Publications

Objectives: Behaviour change interventions may support physical activity behaviour in people with chronic respiratory disease. The most effective interventions for long-term physical activity behaviour change in this cohort remains unclear. This aim of this study was to explore the use and perceptions of behaviour change interventions by both providers of physical activity programmes for people with chronic respiratory disease and by people living with chronic obstructive pulmonary disease (COPD) in The Republic of Ireland.

Design: Two anonymous online and paper-copy cross-sectional surveys, piloted and mapped to the COM-B model of behaviour change, were distributed via social media and relevant gate-keepers …

The Role Of Top-Down Appetite Self-Regulation In The Development Of Healthy Eating Behaviors Among Children: A Narrative Review And Socialization Framework, David J Bridgett, Sheryl O Hughes, Matthew Broussard, Daniela Mccourt, Christina M Croce, Jennifer O Fisher

Faculty, Staff and Students Publications

Appetite self-regulation (ASR) among children is thought to have a fundamental role in shaping the development of healthy eating behaviors, dietary intake, and growth during childhood. Parallel to developmental frameworks for understanding "general" self-regulation among children, ASR has been described as involving children's use of "top-down" cognitive processes to moderate "bottom-up" biological drives around food approach and avoidance in the interest of achieving desired eating behaviors or outcomes. Whereas bottom-up ASR processes during early childhood are well characterized, particularly in the context of dysregulation and obesity risk, the role of top-down ASR processes in the development of healthy eating behaviors …

Influence Of Weekend Social Jetlag On Glucose Tolerance Testing, Ariana Khzarjyan, Srushti Wagh, Graham Mcginnis

Kinesiology and Nutrition Sciences Student Research

Background: Circadian rhythms regulate physiological and metabolic functions across a 24-hour cycle. However, modern lifestyles often disrupt these rhythms. A common example is weekend schedule shifts, when people sleep and wake later than on weekdays, a phenomenon referred to as social jetlag (SJL).

Purpose: The purpose of this study was to; 1) determine whether chronic SJL leads to impaired glucose tolerance, and 2) determine if acute changes in glucose tolerance occur following a weekend of social jetlag (SJL).

Methods: Fifteen male C57BL/6 mice on a normal chow diet were used in this study. To model social jetlag (SJL), mice were …