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Investigating the role of mammalian SWI/SNF chromatin remodeling complexes in lymphocyte differentiation and function
No full textThe dynamics of chromatin architecture and accessibility permit healthy cell type-specific biology, which when dysregulated, can lead to various human diseases. The mammalian SWI/SNF (mSWI/SNF) family of complexes are ATP-dependent, multi-subunit molecular machines that alter DNA-histone interactions to generate accessibility at key gene regulatory elements that control gene expression. Importantly, mutations in SWI/SNF subunit genes occur in over 20% of cancers emphasizing their protective functions in normal cell processes and their increasingly recognized and mechanistically interrogated roles in oncogenesis. The role for mSWI/SNF complexes in modulating chromatin accessibility in the setting of lymphocytes is relatively understudied due to technical limitations in experimental methodologies and complexities of maintaining primary cells in culture. These studies aim to uncover the functional contribution of mSWI/SNF localization, accessibility generation, and gene expression programs in healthy cellular processes including T cell exhaustion and B cell maturation, and within B cell malignancies.
To understand the role of SWI/SNF in T cell activation and exhaustion, we used transient or chronic antigen-independent stimulation across early-activation and late-exhaustion timepoints in CD8+ human T lymphocytes. SWI/SNF occupancy, accessibility generation, and downstream gene expression, in the absence or presence of SWI/SNF genetic and pharmacologic modulators, were evaluated through integrative genomics-centered approaches, including CUT&Tag, ATAC-seq and RNA-seq. We determined that SWI/SNF chromatin targeting, and activity specifically modulates distinct and temporally controlled stages of T cell activation and exhaustion. Furthermore, chemical and genetic perturbation of the SWI/SNF complex enhance T cell persistence and CAR-T expansion. These studies uncovered the contributions of SWI/SNF in regulating T cell activation and exhaustion and highlight the potential to modify current immunotherapy therapies to increase CAR-T fitness.
In addition to the chromatin architecture changes that accompany stimulation conditions in T cells, B cells undergo similar dynamic chromatin rearrangements during differentiation and maturation. Consequently, we investigated whether SWI/SNF localization directs chromatin remodeling to regulate cell-type specific RNA expression in differentiating B cell types. Pro-B, pre-B, immature B, mature B and other specialized B cells were isolated using cell-surface markers and genomic methodologies were performed to investigate SWI/SNF localization, accessibility generation, and resultant gene expression programs. These results uncovered that SWI/SNF localizes at transcription factor-specific enhancers to generate accessibility at critical lineage-specific B cell genes in cell-types across differentiation.
A distinguishing feature of B cell malignancies is the dysregulation of proper B cell development. The BCL7 subunit, a dedicated and evolutionarily conserved component of the SWI/SNF family, is disproportionately mutated in B cell malignancies. Importantly, the functional dissection of BCL7 in biochemical integrity, genomic targeting, chromatin remodeling activity in cells and effect on downstream gene expression has yet to be fully characterized. In these studies, the role of BCL7 in SWI/SNF biochemical activity was explored using CRISPR/Cas9-engineered human cell lines and purification of BCL7A-null, -wild-type and -mutant complexes. BCL7 structural domains and disease variants were functionally characterized through SWI/SNF complex incorporation and integrity. Lastly, the role of BCL7 in SWI/SNF localization, chromatin accessibility and gene expression were examined in B cell lymphoma cell lines. Taken together, these findings provide new mechanisms underlying the functional consequence of BCL7-loss in B cell lymphomas.
Collectively, these studies uncover SWI/SNF chromatin remodeling complex activities in lymphocytes during basic immune cell processes and in human disease, and highlight the distinct contributions of mutated subunits in the setting of B cell malignancies.Biological and Biomedical Science
Chemical Composition of Spitless Tobacco and Nicotine Pouch Products Commercially Available in Northern European and North American Markets: A Targeted Review of Manufacturing Processes and Harmonized Secondary Analysis Evaluating Impact on Dental Health
No full textSales of moist snuff, snus, and nicotine pouch products (NPPs) have grown despite declining use of traditional tobacco products. We compare the differences in manufacturing processes and chemical composition of these products across North America and Northern Europe by performing a targeted review and harmonized secondary analysis of published datasets (2008–2025), evaluating implications for dental health. Reported values were unit-standardized; tobacco-leaf products were converted to dry-weight basis (DWB) where possible. Free nicotine (%) came from source data or was derived via the Henderson-Hasselbalch approximation (pKa 8.02). Conventional moist snuff exhibited the highest and most variable TSNAs, while snus generally showed lower TSNAs but substantial free-nicotine fractions at higher pH. NPPs were heterogeneous: most datasets reported basic pH and high free-nicotine percentages, and although TSNAs were frequently below detection limits, several products exceeded detection limits. Even where TSNAs and HPHCs are reduced (snus, NPPs), detectable toxicants remain. Prolonged use is linked to localized oral injury and periodontal risk; evidence for long-term outcomes is limited for NPPs. These findings underscore the need for greater regulation and education around the potential harms of all smokeless tobacco and nicotine products, including those positioned as harm-reduction alternatives. For dental practice, these findings support routine screening for mucosal changes and periodontal risk in users of moist snuff, snus, and nicotine pouches, with counseling on pH-driven free-nicotine exposure.Extension Studie
Alliances, Aggression, and Regional Cooperation: An Arctic Case Study on Small State Alliance Formation
No full textThis thesis proposes a new theoretical framework through which I explore the
complexities of small state alliance behavior using the Arctic as a regional case study.
My theoretical model challenges the core assumptions of traditional realist theories, and
contends that when there is an effective mechanism for regional cooperation, the impact
of aggression can be mitigated and small states are therefore less likely to pursue alliance
formation. I use a mixed-methods approach to analyze regional cooperation, Russian
aggression, and small state alliance data from 1947 to 2024, to understand the interplay of
these variables using multilevel modeling and moderation regression analyses. My results
reveal that regional cooperation, particularly through the Arctic Council, is effective at
moderating the relationship between aggression and alliance formation, showing that
when cooperation is high, it mitigates the impacts of aggression so that small states are
less likely to form new alliances despite surges in aggressive behavior. Alternatively,
when cooperation is low, escalations in aggression are far more likely to increase small
state alliance formation. The research contributes to small state alliance scholarship,
showing the importance of cooperative mechanisms as a tool for small states to leverage
as a means of securing autonomy, increasing influence, and mitigating the impacts of
aggression.Extension Studie
Equity in Flood Mitigation Funding: Analyzing Social Vulnerability and Public Investment in Houston, Harris County, TX
No full textFlooding is the most frequent and financially damaging natural disaster in the United States, causing more than 8 billion (USD) in annual damages (University of Maryland & Texas A&M University, 2018). With over 30 million Americans living in high-risk flood zones, climate change is expected to further intensify the frequency and severity of flood events (US Water Alliance, 2020). While investments in flood infrastructure aim to reduce risk, mitigation efforts often fail to address deep-rooted inequalities. Research has shown that low-income communities, communities of color, and other vulnerable groups face greater risks and longer recoveries due to geographic exposure, limited resources, and exclusion from decision-making (Villa et al., 2020).
In August 2017, Hurricane Harvey struck the Houston area, flooding over 200,000 homes, with the most severe impacts falling on socially vulnerable communities. In the year that followed, Harris County voters approved a $2.5 billion bond to fund flood mitigation projects. This major investment raised questions about how mitigation resources were distributed and whether funding would reach those most in need.
This thesis analyzes the relationship between social vulnerability and the allocation of flood mitigation funding in Harris County. It examines whether bond and housing buyout funds were distributed equitably across watersheds relative to community need, using the Centers for Disease Control and Prevention’s Social Vulnerability Index (SVI) as a measure of vulnerability. A distributive equity framework is applied to evaluate whether funding aligned with both exposures to flooding and social disadvantage.
This study analyzes funding across 22 watersheds, aggregating census tract-level SVI data to each watershed. It examines bond and buyout funding allocated using dependent variables: total funding and funding normalized by square mile, per capita, and per home flooded. Independent variables include overall SVI and four CDC-defined themes: Socioeconomic Status, Household Composition & Disability, Minority Status & Language, and Housing Type & Transportation.
Regression models indicated statistically significant negative relationships between bond funding per home flooded and several SVI indicators: Socioeconomic Status (p = .003), Racial & Ethnic Minority Status (p .001), and Overall SVI (p = .011). These findings suggest that more socially vulnerable watersheds received proportionally less mitigation funding relative to the severity of their flood damage. No significant relationships were found between SVI and housing buyout allocations, indicating that investments were not systematically directed toward the most at-risk communities.
These results highlight a disconnect between equity goals and implementation. Despite including SVI in project scoring, Harris County’s funding patterns did not equitably reflect vulnerability when adjusted for flood impact. These findings underscore the need for more intentional and targeted equity measures in flood mitigation planning.Extension Studie
Observation of the Yamaji effect in a cuprate and FL* theory of the pseudogap
No full textPhysicsVersion of Recor
Thriving from Work Questionnaire Frequently Asked Questions
No full textThe Thriving from Work Questionnaire Frequently Asked Questions document describes thriving from work and the Thriving from Work Questionnaires, as well as what these instruments measure and why measuring thriving from work is important.Version of Recor
Public Moral Hazard in Solutions to Private Moral Hazard, Illustrated by Macro-Financial Policy Regimes Response to Hélène Rey
No full textPowerful states should avoid using their power and international organisations they dominate to prescribe general measures to developing-economy states because we have not yet overcome our own obvious problems. Doing so also harms our position in the world. Good policies can speak for themselves. We can usefully try to describe our mistakes, problems, and what we think we have learned. There are important illustrations in the 2022-23 inflationary and banking problems. They are rooted in moral hazard within and across organs of the state, which are problems still largely ignored within political economy and science.Version of Recor
Automatic Enrollment with a 12% Default Contribution Rate
No full textWe study a retirement savings plan with a default contribution rate of 12% of income, which is much higher than previously studied defaults. Twenty-five percent of employees had not opted out of this default 12 months after hire; a literature review finds that the corresponding fraction in plans with lower defaults is approximately one-half. Because only contributions above 12% were matched by the employer, 12% was likely to be a suboptimal contribution rate for employees. Employees who remained at the 12% default contribution rate had average income that was approximately one-third lower than would be predicted from the relationship between salaries and contribution rates among employees who were not at 12%. Defaults may influence low-income employees more strongly in part because these employees face higher psychological barriers to active decision making.Author's Origina
Absolution
No full textMy thesis project was inspired by the story of Curtis Flowers – an innocent man tried six times in Missouri for the same murder. Mr. Flowers sat on death row for more than twenty-three years before his conviction was finally overturned by the U.S. Supreme Court in 2019. Currently there are more than 2,300 people sitting on death row in the United States – historically more that 4% of all people executed in the United States are later exonerated.
Typically on death row we might expect to find a priest helping a convicted murderer find forgiveness in the closing hours of his life. But what if it was the priest who actually needs forgiveness?
In my play Absolution, Michael Ryan sits on death row in East Texas after being convicted of the murder of his abusive father. On the day of his scheduled execution, he is visited by his older brother Brennan. Brennan is a priest who has counseled inmates on the same death row unit for several years.
In this play we put the whole idea of forgiveness under the microscope – what it means to forgive and how this concept intersects with religion and reality. We come to find out that a sister committed a ‘mortal sin’ by taking her own life and as such she never had a chance to ask for forgiveness – so what does that mean for her soul? The prison guard, a devout Christian, has no place in his heart for forgiveness while at the same time sees his job as carrying out the Lord’s work. Michael has made peace with his fate even after accepting the truth that he is sitting on death row in the place of the true killer, seeing it as a sacrifice for his brother. His sole concern is for his brother to find his own forgiveness.
The Bible says that a greater love has no man than this - that a man lay down his life for his...brother. This adage is put to the test in my play Absolution
Is Pay Transparency Good?
No full textCountries around the world are enacting pay transparency policies to combat pay discrimination. Since 2000, 71 percent of OECD countries have done so. Most are enacting transparency horizontally, revealing pay between coworkers doing similar work within a firm. While these policies have narrowed coworker wage gaps, they have also led to counterproductive peer comparisons and caused employers to bargain more aggressively, lowering average wages. Other pay transparency policies, without directly targeting discrimination, have benefited workers by addressing broader information frictions in the labor market. Vertical pay transparency policies reveal to workers pay differences across different levels of seniority. Empirical evidence suggests these policies can lead to more accurate and more optimistic beliefs about earnings potential, increasing employee motivation and productivity. Cross-firm pay transparency policies reveal wage differences across employers. These policies have encouraged workers to seek jobs at higher paying firms, negotiate higher pay, and sharpened wage competition between employers. We discuss the evidence on effects of pay transparency, and open questions.Version of Recor