Stroke is the leading cause of adult disability in the United States, with motor impairment as the most common long-term symptom. How lesion location shapes motor deficits and recovery remains unclear. We are investigating how strokes in the primary motor (M1), secondary motor (M2), and primary sensory (S1) cortices differentially affect skilled movement using high-resolution 3D kinematic analysis of a reach-and-grasp task in mice. Mice were trained to stable performance, followed by photothrombotic stroke induction in M1, M2, or S1. Kinematic data was collected longitudinally (days 1-28 post-injury). Movement parameters, including trajectories, velocities, will be quantified using custom 3D kinematic analysis. We hypothesize that lesions in M1, M2, and S1 would produce distinct kinematic profiles despite similarly impaired task success outcomes. Specifically, M1 lesions will disrupt execution, particularly grasp and supination; M2 lesions will impair planning and sequencing, increasing variability and delaying initiation; and S1 lesions will disrupt sensory feedback, leading to abnormal corrections and grasp modulation. These findings will identify region-specific mechanisms of motor control and recovery, informing targeted therapeutic strategies after stroke.

Metabolism has historically been understood as a passive regulator of cell health, yet emerging evidence has demonstrated that it is a likely driver of cell differentiation and can even regulate the processes of cell fate. Given the potential for metabolism to shape cell fate and that cortical cytoarchitecture is known to be altered in many neurodevelopmental disorders (NDDs) and neuropsychiatric disorders (NPDs), we hypothesized that there is a direct relationship between metabolism and cortical cell composition in NDDs and NPDs. To test this, we are utilizing a Perturb-Sequencing screen in cortical organoid models. We have constructed a library of 50 candidate metabolic genes also identified in NDDs by leveraging our lab’s preexisting metabolic atlas, which we have perturbed in our organoid systems. We have verified recapitulation of canonical cell types with immunofluorescence and have harvested our organoids for scRNA-seq, with which we have conducted rigorous computational analysis using R to identify fate changes resulting from perturbations of these genes. We have so far identified possible gene candidates to investigate further, but in all this project has provided us with evidence that metabolic genes are capable of shifting cell developmental trajectories and has also demonstrated how manipulating metabolic processes can contribute to overall cytoarchitecture.

The limbus is the border between the eye’s cornea and sclera, where it houses limbal stem cells (LSCs)—cells integral to corneal epithelial regeneration following regular shedding or injury. Limbal stem cell deficiency (LSCD) is characterized by an inadequate LSC population and can lead to corneal blindness. The Canonical Wnt Signaling Pathway is required for the survival and proliferation of LSCs. A recent study reported a conflicting result: LY2090314, a small-molecule Wnt activator, decreased proliferation, increased stem cell differentiation, and exerted cytotoxic effects in LSC explant culture at a high concentration of 10 nM. This study aims to establish a dose-response curve for LY2090314 in LSC explant culture. LSC expansion was evaluated by cell growth rate, cell morphology, and stem cell population when treated with LY2090314 in a dose-dependent manner. We aim to compare LSC expansion across three treatment groups: untreated control, LiCl (a Wnt activator), and LY2090314 at low and high concentrations. Immunofluorescence will be employed to stain for Cytokeratin (K)12, K14, and p63a (markers of stemness maintenance), pan-cytokeratin (epithelial cell marker), and vimentin (mesenchymal cell marker). Additionally, we characterized the stem cell population by size (≤12 µm). Further study is needed to determine the optimal dose of LY2090314 to promote LSC proliferation rather than induce differentiation.

Major Depressive Disorder (MDD) affects millions of people worldwide, and approximately one-third of patients develop Treatment-Resistant Depression (TRD), defined by a nonresponse to multiple antidepressant treatments. Increasing evidence suggests that inflammation may play an important role in depression pathophysiology, yet the relationship between systemic inflammation and brain microstructure is not fully elucidated. This project investigates whether diffusion magnetic resonance imaging (dMRI) metrics can provide a noninvasive marker of neuroinflammation in TRD. Baseline data from patients with TRD and healthy control participants are analyzed, including dMRI-derived measures of white matter microstructure and peripheral inflammatory biomarkers. Diffusion measures include neurite density, orientation dispersion, and free water, which reflects extracellular water and may serve as a proxy for neuroinflammation. Linear regression analyses examine associations between inflammatory biomarkers, depression symptom severity, and region-specific white matter microstructure, while including age, sex, and body mass index as covariates. Preliminary findings are expected to demonstrate elevated free water and increased levels of inflammatory biomarkers in TRD patients compared to controls. Identifying dMRI correlates of inflammation may help clarify biological mechanisms of depression and provide a less invasive diagnostic tool to guide treatment.

Nodding syndrome (NS) is a pediatric epileptic encephalopathy affecting children in regions of Eastern Africa and is characterized by repetitive head nodding, cognitive decline, and progression to other seizure types. This cross-sectional study evaluated multiplex families from NS-affected districts of northern Uganda using standardized clinical phenotyping and ambulatory EEG recordings. Among 114 EEGs reviewed, 39 were classified as abnormal, with abnormalities most frequently observed in individuals with NS or NS+, though also present in relatives with epilepsy alone and in clinically unaffected participants. Common EEG abnormalities included focal or multifocal epileptiform discharges, generalized spike-and-wave activity, spike-wave activation during sleep, dyshormia, and generalized background slowing, with generalized and sleep-activated abnormalities occurring predominantly in individuals with NS. At the family level, abnormal EEGS in two or more members were identified in over half of multiplex families, and several families demonstrated abnormal EEG findings in clinically unaffected relatives. These findings indicate that NS is associated with widespread epileptic network dysfunction and shares electrophysiological features with other familial epilepsies, supporting the interpretation of NS as part of a broader epilepsy spectrum rather than a distinct neurological entity. The electrophysiological profile of NS and its relationship to epilepsy within affected families remains poorly understood.