Hippocampal neuronal networks encode various task-relevant variables and are modulated by the behavioral state. With escalating cognitive demands, principal cells reorganize to prioritize salient information and filter stimuli. However, the specific inhibitory circuit mechanisms that drive these population-level changes remain poorly understood. Distinct interneuron types shape principal cell dynamics via inhibition of different regions across the somatodendritic axis of principal neurons. Among these are Oriens-Lacunosum Moleculare (O-LM) interneurons which inhibit the distal dendrites of the CA1 principal neurons and modulate local field potential (LFP) theta oscillations (4-12 Hz), an electrophysiological rhythm tightly linked with information encoding and mnemonic processing. Given their strategic role in distal dendritic excitability, we hypothesize that O-LM interneurons play a central role in shaping hippocampal population dynamics across graded levels of cognitive demand. To address this question, we have developed a head-fixed linear treadmill track to voltage image the hippocampus of mice navigating tasks with distinct cognitive demand. Using a Cre-dependent viral strategy to achieve specific access to O-LM interneurons, we will compare O-LM population subthreshold and suprathreshold dynamics in three conditions: a simple locomotion task, a more involved spatial navigation task, and a complex olfactory working memory task within the same environment. Through this analysis, we hope to disentangle the inhibitory popu

The positioning and coordination of retinal pigment epithelium (RPE), photoreceptors and retinal neurons is crucial to the conversion of light to neural signals that allows vision to be carried out by the eye. Disruption of this crucial system can result in vision loss by progressive retinal dysfunction and degeneration. Here we show that full-field flash electroretinography (ERG) testing reveals unexpected irregularities in bipolar, Müller and RPE cell-driven responses in ABCA4 KO mice compared to WT controls. ERG waveform analysis and Naka-Rushton fits demonstrate b- and c-wave amplitude reductions and altered Vmax and K values in some albino WT mice compared to ABCA4 KO mice. These findings directly contrast expectations that ABCA4 loss aggravates or exacerbates retinal and RPE dysfunction. This leads to the inference that ABCA4 has a much more complex function within retinal signaling pathways, and pigmentation and age are variables that may have a more extreme effect on retinal light processing than previously thought. Together, these results indicate that retinal dysfunction associated with ABCA4 loss does not follow a simple loss of function model and requires continued investigation to clarify true underlying patterns. This project highlights the importance of unknowns within inherited and de novo retinal diseases, as well as making room for both correlation and divergence from existing models into biological and experimental variability when interpreting telling data.

Iron is an essential nutrient whose cellular homeostasis is tightly regulated by a complex network of proteins. Tumor cells hijack this metabolism to fuel proliferation, creating an iron-rich microenvironment by upregulating uptake and suppressing export. While core regulatory proteins are known, tissue-specific iron networks remain largely uncharacterized due to the sensitivity limitations of traditional Data-Dependent Acquisition (DDA) proteomics. To address this, we employed Data-Independent Acquisition Mass Spectrometry (DIA-MS) to map the iron proteome across a diverse panel of cancer cell lines.We quantified over 9000 proteins across the panel.We utilized unsupervised clustering of transcriptomic data to select a cell line panel that maximizes proteomic diversity while minimizing redundancy. Our analysis delineated a conserved core of iron regulators while uncovering tissue-specific hubs, notably the upregulation of glycolysis and HMG-CoA reductase (HMGCR) in lung adenocarcinoma (A549). These findings provide a scalable framework for identifying precise therapeutic targets for iron-chelation therapies and expand our understanding of the iron proteome in oncology.Furthermore, this work aims to expand our fundamental understanding of the iron proteome, with translational implications extending to other iron-dysregulatory pathologies, including beta-thalassemia and hemochromatosis.

Trichomonas vaginalis (Tv) is a protist parasite that causes trichomoniasis, a sexually transmitted infection, with rising drug resistance. Once a Tv cell enters the host urogenital tract, the Tv cell uses its flagella to attach to the epithelium. Because flagella are important to Tv’s survival in the host urogenital tracts, targeting costa, a filament thought to provide structural support for flagella, may be a promising approach to develop a new treatment. However, an insufficiency of molecular understanding of the costa structure hinders the development of a new treatment. Here we show a high-resolution structure of costa from cryogenic electron tomography of the costa protein in its near-native state.

Aging is a natural process that affects all tissues. Deregulation of metabolism is central in aging, with the efficiency of metabolic pathways being a key determinant of the health of different cell types. Earlier work in our lab showed that the mitochondrial pyruvate carrier (MPC) is deeply intertwined with metabolism and its inhibition led to the reactivation of mouse hair follicle stem cells (HFSCs), thus reversing the effects of aging. To investigate the drug’s effects on the liver – a vital organ for general metabolic capacity – we treated aged mice with UK-5099. Through whole genome bisulfite sequencing in the liver genome, we looked at the methylation changes and identified several differentially methylated loci (DMLs) due to aging and treatment. The UK-5099 had a remarkable effect on the methylome, reversing almost all aging DMLs back to the levels found in young. We assessed the RNA levels of each cohort to test the correlation between methylation and transcription, and identified several genes whose RNA levels were altered by UK-5099 treatment. We then examined gene signatures relevant to the aging liver, such as ones for collagen and senescence, and saw a general reversal of transcript levels due to treatment. We confirmed the RNA-sequencing results by immunofluorescence and immunohistochemistry for several markers, such as collagen and p16. Our findings suggest that MPC inhibition can reverse the methylome and transcriptome of the aged murine liver, placing pyruvate metabolism at the nexus of hepatic aging.