The composition of metropolitan governance has many effects on land use decisions, budget allocations, housing development, transportation planning, and racial, economic, and social equity in urban areas. However, there has been little academic inquiry into the effect of regional governance structure on transportation accessibility. This paper seeks to examine statistical linkages between regional governance fragmentation and trends toward and away from greater transportation accessibility in metropolitan areas. I perform a comparative statistical analysis of 47 of the 50 largest Metropolitan Statistical Areas, examining census data from 2002 to 2022 and transit accessibility data from the University of Minnesota Accessibility Observatory from 2014 to 2021 to examine this relationship. The causal factor I investigate is metropolitan governance fragmentation, which I capture through a Governance Fragmentation Index (GFI). The dependent variable, transportation accessibility, is captured through an Accessibility Gap Index, which categorizes transportation access through accessibility levels throughout each Metropolitan Statistical Area, utilizing data from the Accessibility Observatory from 2014 to 2021. My analysis controls for potential confounding variables, such as geographic area, population size, poverty levels, and region. I expect to find that lower levels of governance fragmentation in a Metropolitan Statistical Area will be associated with greater gains in transportation accessibility. Whether or not a significant relationship is identified, the research conducted will contribute to literature and ongoing research surrounding metropolitan governance and transportation accessibility.

When a cell undergoes stress conditions, such as oxidation or aging, an increase in protein instability can occur and prevent proper cell functions. Small Heat Shock Proteins (sHSPs) are molecular chaperones that work to maintain a healthy proteome by associating with misfolded “client” proteins to delay aggregation under such conditions. HSPB5, a human sHSP, is ubiquitously expressed throughout the body. HSPB5’s disease mutant, R120G, is a defective chaperone associated with cataracts and desmin-related myopathy. It is still unknown how this mutation is detrimental despite many years of research. My research aims to understand how this mutation retunes the electrostatic properties of HSPB5, affecting its chaperone activity. Residue R120 is part of an electrostatic network that helps create an important structural feature in the folded region of HSPB5, the alpha-crystallin domain (ACD). In the unmutated (WT) protein, the ACD surface is overall positively charged. Substitution of the positive R120 to glycine alters both ACD’s structure and electrostatics. I generated two mutants, R120K (retaining positive charge) and R120D (switching to negative charge) to investigate how R120 plays a role in ACD’s conformation. Using a negatively-charged molecule, ATP, as an “electrostatic” probe in 2D NMR, I observed differences between its binding affinity to my R120 variants. I found that only R120K ACD behaves similar to WT ACD, suggesting a possible correlation between charge potential and ACD’s interactions with ATP. Currently, I am investigating if charge potential affects chaperone activity through aggregation assays with a client protein, human γD-crystallin, found in the lens and implicated in cataracts. I predict that WT and R120K, with similar electrostatic properties, will have similar chaperone activity. R120G and R120D, prevalently in an “active” state, will have higher chaperone activity. Understanding how such mutations affect HSPB5’s conformations and chaperone activity is a step forward in understanding sHSPs’ chaperone mechanism.

Small heat shock proteins (sHSP) are a family of molecular chaperones whose function is to delay the harmful aggregation of other proteins. Protein aggregation is associated with neurological disorders such as Alzheimer's disease and Parkinson's disease. In many tissues, multiple sHSPs are coexpressed and tend to assemble into hetero-oligomers. Hetero-oligomers are complexes of two or more different protein species. The extent and mechanism by which these hetero-oligomeric complexes form is yet to be fully understood. The goal of my discovery-driven research is to assess how the properties of sHSP hetero-oligomers differ from the properties of homo-oligomers. In my project, I focus on three sHSPs that are highly expressed in muscle: HSPB1, HSPB5, and HSPB6. Each of these proteins exhibit different behavior when on their own. HSPB1 and HSPB5 form a distribution of large homo-oligomers, whereas HSPB6 forms a small homo-dimer. One of the most characteristic properties of the small heat shock proteins is formation of oligomers that span different sizes. Thus I am primarily determining the sizes and composition of the sHSP hetero-oligomers. I performed a comprehensive study to characterize the sizes of the hetero-oligomers using three complementary methods: analytical size exclusion chromatography, mass photometry, and native gel electrophoresis. I have found that HSPB6 is able to readily incorporate into hetero-oligomers as the concentration of the other sHSP is increased, and that the complexes are formed in a distribution of intermediate sizes. I am currently working on assessing the ability of the hetero-oligomers to act as molecular chaperones by aggregation assays. I predict the hetero-oligomers will delay protein aggregation more efficiently than HSPB6 on its own. The findings of my project give insight into why sHSPs are coexpressed and form hetero-oligomers in cells. Understanding these hetero-oligomers sheds light into the complex pathways of sHSP function. 

In this project, I explore the settler colonial dynamics that shape Wilderness Therapy, a for-profit carceral institution that has come under scrutiny for allegations of abuse despite their mission of curing “troubled teens” through the healing benefits of the outdoors. Specifically, I investigate the relationship of Wilderness Therapy to Indigenous land dispossession, violent cure-based medical models, and power and privilege within incarcerated communities. As someone who has been to Wilderness Therapy, I am interested in exploring the web of entanglements among carceral institutions, and how my experience and research can dismantle the carceral state and prioritize equitable reparations. My research takes the form of a novel written in a hybrid structure that braids fiction and nonfiction sections. The fiction part of my novel follows a student through her journey at Desert Destinies, a made-up Wilderness Therapy Center based on the average statistics of my research. The thesis of the nonfiction work postulates that Wilderness Therapy perpetuates slow colonial violence, meaning violence that replicates colonial structures and takes place in hidden ways over such a long period of time that it is invisibilized and naturalized. My research has taken many different forms and has been guided by various methodological approaches, including ethnographic research; close readings of archival documents, including my own journals from my time incarcerated; bibliographic research in the fields of Indigenous Studies, Settler Colonial Studies, and the Environmental Humanities; and creative writing. Through this project, I hope to imagine a decolonial future beyond the carceral state in which we address the slow violence inflicted by society on a personal and community level.

The heart is one of the most mechanically active organs in the body. In a mechanism known as the “Bainbridge Reflex”, the heart rate accelerates in response to the mechanical stretch induced by the increase in venous return. The cardiac pacemaker controls heart rate, and while stretch-activated channels have been identified in cardiac tissue, their molecular identity remains unknown. We hypothesize that PIEZO channels are the molecular determinant of the stretch-dependent heart rate acceleration responsible for the Bainbridge reflex. Using quantitative polymerase chain reaction (qPCR), we assessed the presence of Piezo1 and Piezo2 transcripts in the pacemaker, atrium, and ventricle of the mouse heart. Our findings revealed that both Piezo1 and Piezo2 are present in the three regions with significantly higher expression in the pacemaker and atria. Combining immunohystochemistry, tissue clearing, and super-resolution microscopy, we analyzed the distribution of Piezo1 and Piezo2 in mouse pacemaker explants. Our results show that Piezo2 is uniformly expressed in the pacemaker and surrounding atrial tissue, whereas Piezo1 exhibits higher expression levels outside the pacemaker. These results were further confirmed at the single-cell level, with immunostaining of Piezo1 and Piezo2 in isolated pacemaker cells (HCN4+) and transitional cells (HCN4-). We observed similar expression levels of Piezo2 in both cell types and increased Piezo1 expression in transitional cells. In addition, we observed distinct localization patterns for Piezo1 and Piezo2 at the subcellular level. Piezo1 predominantly localizes to the sarcolemma, while Piezo2 exhibits a striated distribution that colocalizes alternately with both the Z- and the M- line of the sarcomere. Given this pattern, half of the Piezo2 bands colocalize with the RyR. These results set the starting point to evaluate the functional role of PIEZO channels in the cardiac pacemaker.