Temporomandibular disorders are characterized by chronic orofacial pain and are strongly associated with stress, yet the underlying mechanisms remain unclear. This study investigates how chronic stress alters neural pathways to drive pain sensitization, with a focus on sympathetic nervous system involvement. We hypothesized that repeated stress enhances interactions between sympathetic and sensory neurons, leading to increased nociception. Female C57BL/6J mice were subjected to a repeated restraint stress paradigm. Pain sensitivity was assessed using von Frey filament testing and the Mouse Grimace Scale. Trigeminal ganglion neurons were labeled using FluoroGold injections to the temporomandibular joint and masseter. Immunohistochemistry was used to examine expression of CGRP, BDNF, and adrenergic receptors, while patch clamp recordings assessed neuronal excitability. Chronic stress significantly reduced head withdrawal thresholds, indicating increased pain sensitivity. Imaging revealed increased co localization of sympathetic markers with sensory neurons, along with elevated CGRP and BDNF expression. Electrophysiological recordings demonstrated heightened neuronal excitability. Pharmacological sympathectomy reduced stress induced hypersensitivity, supporting a causal role of sympathetic signaling. These findings show that chronic stress drives neuroplastic changes that enhance sympathetic sensory coupling and promote persistent pain, identifying sympathetic pathways as targets for chronic orofacial pain.

This project examines the role of diet in shaping metabolic health across the life course as part of a broader book chapter on nutrition and metabolic outcomes. Using a life course framework, it considers how dietary exposures influence health over time and how these effects are shaped by social, environmental, and structural conditions. The project focuses specifically on diet-related pathways, including dietary patterns, glucose regulation, lipid metabolism, inflammation, and the gut microbiome, and explores how these processes contribute to metabolic outcomes across stages such as pregnancy, infancy, childhood, adolescence, and adulthood. The research will be carried out through literature searches in PubMed and other academic databases, followed by review and synthesis of peer-reviewed studies. Evidence tables will be developed to organize major findings, and the final written work will summarize the diet-focused portion of the chapter while also incorporating tables or figures to present key concepts clearly. Research progress will also be presented during Undergraduate Research Week. The significance of this project lies in its emphasis on diet as a major contributor to metabolic health across the life course, while also recognizing that nutritional outcomes are shaped by broader contexts beyond individual behavior alone.

Nausea is a visceral and unpleasant sensation that serves as a protective mechanism from toxins. Past research has implicated the vagus nerve as a major component in detecting toxins in the GI tract, and it is known that some vagal neurons project to the area postrema (AP) and nucleus of the solitary tract (NTS), sites in the brain that detect circulating signals for nausea. It is hypothesized that some compounds bind to receptors on cells specific for nausea, and that signaling by these cells leads to the nausea response. This project sought to identify both natural and synthetic compounds that induce activity in the AP/NTS in order to characterize the molecular mechanisms that underlie detection of toxins by vagal neurons. Activity in vagal neurons was measured in-vitro via calcium imaging. Activity in the AP/NTS was measured in-vivo via immediate-early gene staining with cFos. In-vitro results indicate that lansoprazole and potassium p-aminobenzoate induce activity in vagal neurons. However, in-vivo activity suggested that neither compound produced activity in the AP or NTS, potentially due to issues in drug delivery/penetration. Understanding these mechanisms will benefit the development of treatments for nausea to aid in situations such as pregnancy and chemotherapy, where discomfort caused by nausea can become maladaptive.

Inclusion of modifications in mRNA decreases exonuclease cleavage and sensing by various pattern receptors, creating "immunosilent" mRNA with increased translation efficiency and thus broadening the application of the mRNA platform. However, the lack of immunogenicity necessary for a robust innate immune response results in inadequate efficacy against immunosuppressive cancers. Our solution was to build and test a novel modified RNA adjuvant to boost immune response. Transfection of murine-derived macrophages with the modified adjuvant drove a significant increase in innate immune activation compared to the unmodified adjuvant, as indicated by IFNβ and IL-6 gene expression measured by qPCR. We hypothesized that the RNA adjuvant modifications rendered it resistant to degradation by endolysosomal exonucleases such as RNase T2, allowing for prolonged sensing of the adjuvant by pattern recognition receptors. In the presence of RNase T2, the modified RNA adjuvant maintained structural integrity while unmodified RNA underwent fragmentation. These results demonstrate the contribution of nucleotide-level modifications in engineering an effective cancer immunotherapy. We speculate that other nucleoside modifications in our adjuvant may similarly lead to decreased enzymatic activity and increased innate immune response. Future work will characterize these modifications. Our adjuvant’s stability and ability to elicit a robust immune response may allow us to build a more effective platform against immunosuppressive cancers.

Cardiac atrophy is a well-known risk factor for cardiomyopathy and overall heart failure. Nutrient deficiency is an essential factor for cell atrophy. However, it remains obscure how nutrient deficiency causes cardiomyocyte death. In the present study, we indicate the critical involvement of ULK1 in protecting cardiomyocytes against nutrient deficiency-induced death. Nutrient deficiency activates ULK1 signaling in H9c2 cells without causing cell death within 30 h; thereafter, cell death occurs with deactivation of ULK1 signaling. During nutrient deprivation, inactivation of ULK1 signaling by pharmacological inhibition with SBI-0206965 or genetic knockdown with silencing induces cardiomyocyte death, which is not attributable to increased autophagic flux or apoptosis. Inhibition of ULK1 under nutrient-deficient conditions reduces intracellular NAD⁺ and NADH. Supplementation of exogenous NAD⁺, but neither nicotinamide (NAM) nor nicotinamide riboside (NR), during nutrient deficiency restores intracellular NAD⁺ and NADH levels and prevents cardiomyocyte death. Among enzymes in the salvage pathway, NAD +  kinase (NADK) is downregulated, with no further decrease in the presence of SBI under nutrient-deficient conditions. In summary, our present study indicates that NADK downregulation and ULK1 activation synergistically preserve the NAD⁺ pool during nutrient stress, thus promoting cardiomyocyte survival. These findings may identify ULK1 and NAD⁺/NADH metabolism as promising therapeutic targets in heart failure.