The cortex, the topmost layer of our brain, is organized into functional regions that enable high-level cognitive functions such as language and future planning. The thalamus, the brain’s sensory relay system, grows in parallel with the cortex in early embryonic development. How cortical areas emerge and the importance of the thalamus in this process are not well characterized. We hypothesize that adult thalamic neurons help guide stem cells to regional identities. To test this, we grew cortical and thalamic organoids, 3D stem cell models of the human brain. Through immunostaining and single-nuclei sequencing of fused thalamic-cortical organoids, we found evidence that the presence of thalamic neurons increases upper cortical layer neurogenesis. Additionally, experiments knocking out NRXN1, a synaptic protein, altered this phenotype. This suggests that the communication between adult thalamic neurons and cortical progenitors may be synaptic.  

Despite Major Depressive Disorder impacting over 250 million people worldwide, antidepressant treatments are relatively ineffective. One reason for this low efficacy is the lack of granularity in the field, as unexplained heterogeneity in susceptibility to depression has been observed even across inbred mice raised in identical conditions. Helplessness is a core feature of depression; therefore, this study utilizes a murine learned helplessness (LH) paradigm as a depression model, designed to induce susceptibility to helpless behavior following inescapable stress. The medial prefrontal cortex (mPFC), a cortical region involved in cognition, working memory, sociability, and emotional control, has been implicated in depression due to altered neural activity. We explored mPFC associated functions such as learning, memory, sociability, and motivation. Data acquired from behavioral assays (i.e., 3-chamber sociability task, novel object recognition, T-maze tasks) were processed in order to extract behavioral features in response to learned helplessness. Temporal analysis during a t-maze learning and working memory task at pre-stress and post-stress timepoints revealed a potential negative correlation between learning acquisition and susceptibility to helplessness. Additionally, by analyzing facial features during a pavlovian discrimination task we identify characteristic facial responses to rewards vs punishment trials which can be used in future research as quantifiable readouts for positive vs negative emotional state. These findings bring us one step closer to more accurate noninvasive diagnostics and a more comprehensive understanding of distinct depressive states, as well as individualized treatments for mental health conditions.   

Toxoplasma gondii is an apicomplexan parasite that infects a large proportion of the human population. Despite its prevalence, key aspects of the parasite’s development remain poorly understood. In particular, the influence of inter-pathogenic signaling on the invasion dynamics, growth, and replication of Toxoplasma has yet to be characterized. Here, we investigated several aspects of the parasite’s capacity for extracellular communication and measured impacts on Toxoplasma’s development. First, we manipulated extracellular environments to study effects on the early stages of invasion and alternative growth patterns. Then, we quantified parasite development by measuring the rates of primary-invading parasites and late-invading parasites to determine whether differences in invasion time points reflect intrinsic infectivity or environmental factors. Finally, we evaluated a dual infection model with Toxoplasma and Chlamydia caviae as a platform to study inter-species signaling. Together, these data advance our understanding of this highly successful parasite and the fundamental principles of infection, establishing a foundation for future studies of inter-pathogenic interactions. 

Fragile X syndrome (FXS) is the most common monogenic cause of intellectual disability and autism spectrum disorder (AS). There are currently no available treatments that dress the root biological causes of FXS. At the circuit level, FXS and ASD are hypothesized to result from an imbalance of excitatory and inhibitory neurons. Recently, we used RNA-sequencing to survey differential gene expression in these neuronal cell types in FXS model (Fmr1 knockout) mice, the main animal model of FXS. We discovered that one gene, Rapgef4/Epac2, a similarly upregulated in both excitatory and inhibitory neurons. Therefore, we hypothesized that inhibiting EPAC2 would rescue atypical behaviors in Fmr1 KO mice. We first assessed whether Fmr1 KO mice demonstrated atypical behavior as compared to control wild type (WT) mice in measures of social withdrawal, anxiety, repetitive behaviors, and sensory hypersensitivity. We tested mice on a three-chamber social preference assay, elevated plus maze, marble burying task, and tactile defensiveness assay. We did not observe a clear phenotype in the elevated plus maze or marble burying. However, Fmr1 KO mice engaged in less social and demonstrated tactile defensiveness in response to repetitive whisker stimulation. Tactile defensiveness, but not social avoidance, was rescued by chronic administration of the EPAC2 inhibitor ESI-05 (10 mg/kg, i.p.). These results better our understanding of the mechanisms affecting FXS and suggest that ESI-05 has potential as a therapeutic for hypersensitivity in FXS.

The order Schizomida (short-tailed whipscorpions) accounts for two families of over 200 species across a mostly pantropical range of soil and cave habitats. Schizomids tend to experience a high degree of endemism, and due to their restricted ecological niches and low vagility, they are at special risk of extinction by ongoing climate change. Hubbardia Cook, 1899 is a schizomid genus with 9 species distributed along Southern California and the Sonoran Desert, with populations from the latter historically experiencing high levels of habitat fragmentation due to aridification. Currently, I am conducting integrative revisionary studies of the genus Hubbardia utilizing morphological and existing ultraconserved element (UCE) genomic data. In doing so, I aim to potentially describe three new species across these imperiled desert oases. This project aims to contribute to a standing biogeographic framework for other relictual North American taxa stranded in similarly fragmented biomes.