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Evaluating Migration of Human Monocytes in an Inflammatory Environment Mimicking Burn-Induced Inflammation in Blood Donor Samples
No full textIn the U.S., more than half a million people are hospitalized for burn wounds every year. These wounds can progress into serious and even fatal injuries due to the immune system’s defense against harmful pathogens with access to bodily tissues through the burn injury. This invasion into bodily tissue can lead to systemic inflammation. One of the by-products of this inflammation is the activation and migration of white blood cells, specifically monocytes, to the site of injury and/or infection to eliminate the microbes and protect the surrounding tissues. While relatively small, inactive monocytes can drastically increase their size in the case of activation via pathogenic infection. Although the general mechanisms are understood, there are significant components of monocyte activity that have not been clearly elucidated. However, it has been shown that these monocytes boast significant prognostic capabilities. The severity and potential outcome of patient injuries can be predicted with considerable accuracy using Monocyte Distribution Width (MDW), or monocyte anisocytosis, which is the difference in monocyte sizes within an individual. In this research, we investigate the activity and size distribution of monocytes under various conditions. It was found that, as expected, the trigger protein (SDF-1α) induced monocyte migration dependent on the concentration used. However, the inhibitor (AMD-3100) markedly reduced migration when used in conjunction with SDF-1α. Also, the activators lipopolysaccharide (LPS) and Pam3CysSerLys4 (PAM) were shown to increase MDW.Extension Studie
Rooted in Resilience: Designing a National Certification for Place-Based Partnership Leaders at StriveTogether
No full textAbstract
In the rapidly evolving field of place-based partnership leadership, there is a critical gap in structured, competency-based training for leaders driving systemic change. This capstone explores my strategic project at StriveTogether, a national network advancing equitable outcomes for children through collective impact, where I led the development of a National Certification for Place-Based Partnership Leaders—a first-of-its-kind initiative designed to professionalize the field and equip leaders with the technical and adaptive skills needed for community transformation.
Rooted in StriveTogether’s Theory of Action and the principles of collective impact, the certification framework leverages competency-based education (CBE) and backward curriculum design to ensure leaders gain knowledge and apply it to real-world challenges. A pivotal shift occurred when the certification expanded beyond executive directors to include proximate leaders with deep community ties but fewer formal leadership opportunities. Early data showed that limiting the certification to executive directors would primarily benefit white women, reinforcing disparities in leadership access. By broadening the model, the certification prioritizes equity in leadership development and creates pathways for those most impacted by systemic challenges.
Throughout this project, I navigated the complexities of leading from the middle—building influence without formal authority while aligning stakeholders with competing priorities. I deepened my understanding of transparent decision-making, active listening, and relational trust, as well as the power of strategic partnerships—mainly through my collaboration with the EdRedesign Lab at Harvard—to expand access to leadership training. Ultimately, this project contributes to the collective impact field by offering a scalable, systemic model for leadership development—ensuring place-based partnership leaders have the skills, relationships, and resources to drive lasting community change. The capstone concludes with the implications for my leadership growth, StriveTogether’s organizational strategy, and the broader sector, emphasizing inclusive leadership pipelines, sustainable project management, and equity-centered, community-driven leadership development.Educatio
Extending STM Capabilities: Multi-Frequency Lock-In Amplification for Closed-Cycle STM and Tip-Controlled Lattice Distortions in WTe₂
No full textScanning tunneling microscopy (STM) is a versatile tool that provides sub-nanometer topographic information, gives access to the electronic structure by measuring the local density of states, and enables local modification of the atomic structure.
This thesis contains research results on two distinct topics related to STM's abilities.
The first part illustrates STM results on the local modification of the lattice structure in the ferroelectric and Weyl semimetal WTe.
Lattice distortions are created using current pulses by an STM tip, leading to in-plane shifts of surface atoms similar in magnitude to previously reported ferroelectric switching in WTe.
In addition, we observe out-of-plane rearrangements of Te atoms, potentially suggesting local perturbations of the Jahn-Teller distortion.
These distortions are accompanied by changes in the local density of states, indicating modifications to the electronic structure.
The lattice distortions extend over nanometer-scale regions and can be repositioned or erased.
This work demonstrates the potential for reversibly tuning the electronic structure of WTe on the nanometer scale.
The second part focuses on improvements to a closed-cycle cryostat STM system using an emerging measurement technique called multi-channel lock-in amplification (MCLA).
The scarcity of helium and the increasing cost of liquid helium production motivate the adoption of closed-cycle cryostats.
However, the elevated vibrational noise levels of such cooling systems limit their usability with STM.
This work illustrates the adoption of the MCLA technique to improve the performance of a closed-cycle STM system.
We developed an open-source MCLA that acquires 72 harmonics. Our implementation is built on an off-the-shelf field-programmable gate array (FPGA) development board, making it affordable and customizable.
The use of MCLA enables a twelve-fold reduction in measurement time, allowing to perform quasiparticle interference mapping, which has not previously been reported for STM systems operated with closed-cycle cryostats.Physic
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
Simultaneous in situ measurements of B cell clonality and single cell transcriptomes
No full textThe B cell response to antigen is carried out within various compartments of different tissues. B cell pathologies often coincide with a malformation of one or many of these tissue compartments, highlighting a direct connection between tissue organization and dysregulation. To better interrogate this connection, spatial transcriptomics has evolved to encompass a suite of new tools that have promised an unprecedented molecular description of whole tissue architecture. A breakout technique in this field is Multiplexed Error-Robust Fluorescence in situ Hybridization (MERFISH). MERFISH is an image-based single-cell transcriptomic tool that leverages optical barcodes to extend the scalability of traditional single-molecule FISH approaches to near transcriptome-level. MERFISH has been used to atlas a diverse range of cell types and states in the brain, liver, and gastrointestinal tract. However, as a probe-based approach, MERFISH was unable to distinguish between highly homologous gene targets such as the components of the B cell receptor, ultimately prohibiting MERFISH from tracking the interactions of specific B cell clones.
Here, I present a technical extension to MERFISH, hereby termed B Cell Receptor MERFISH (BCR-MERFISH), that equips the standard MERFISH measurement with the ability to assign clone IDs to plasma B cells. BCR-MERFISH uses an orthogonal optical barcoding set to detect and label IGHV, IGKV, IGLV, and Fc usage within single cells. Importantly, BCR-MERFISH is co-stainable with standard MERFISH libraries and places unique plasma B cell clones in their defined, native tissue contexts – allowing the user to identify key cellular interactions that occur between unique clones and their neighboring cells. I have validated the accuracy of BCR-MERFISH through transient transfections of specific IGHV and IGKV genes in HEK293 cells, a transgenic mouse with a biased expression of a known IGHV/IGKV pair, and by comparing its results to BCR-sequencing of matched ileal slices from wild-type mice.
I have used BCR-MERFISH in germ-free mice to reveal an enrichment of recurrent plasma cell clones within the lamina propria compared to that of specific pathogen-free mice – a phenomenon that was suggested by an enrichment of the same recurrent clonotypes found in the Peyer’s Patch germinal centers of germ-free mice.
I show that BCR-MERFISH can capture the spatial distribution of specific clones across both the mucosal and intestinal axes. Regarding the mucosa, the lamina propria of the villi recruits Ccr9+ plasma cells via the secretion of Ccl25. I demonstrate that in wild-type specific pathogen-free mice, that the distribution of unique plasma B cell clones is not dependent on the sequence of the BCR. However, despite the uniformity within the layers of the villus, certain plasma cell clones show significant enrichment within proximal, medial, and distal ileum. Furthermore, certain clones even exhibit a common co-occurrence with either their sisters or other specific plasma B cell clones. Together, I believe that BCR-MERFISH offers a path to many new insights into a wide range of immunological questions that require a more comprehensive description of the immune tissue environment compared to other existing technologies.Biological and Biomedical Science
Romeo, Juliet, and Cheetos
No full textTessa is finally able to talk to her best friend, Mia, again, which is great. The only issue is that Mia committed suicide a year ago, and the Mia that’s currently residing in Tessa’s head isn’t the same supportive friend Tessa remembers. Not to mention, the whole normal-people-don’t-have-dead-people’s-voices-in-their-heads thing.
Despite feeling crazy, Tessa is glad when Mia tries to help her navigate junior high, deal with her overprotective parents, and get a part in Romeo and Juliet. When Tessa has her first crush, starts to make friends, and gets asked to her first dance, Mia gets jealous and angry. Dark thoughts start to invade Tessa’s mind as Mia becomes harder and harder to control. Tessa deals with anxiety attacks, depression, therapy sessions, and the trauma of loss while she tries to rebuild her world and find a new sense of normal.Extension Studie
The Promise and Hazards of Armed Self-Protection: Analyzing the Racial and Gender Implications of Justifiable Homicide and the Effects of ‘Stand Your Ground’ Laws
No full textIn response to a growing national desire for armed self-protection, most states have passed Stand Your Ground (SYG) laws. These laws expand legal immunities for the use of self-defense and allow law enforcement personnel to preempt jury rulings of justifiable homicides. In this thesis, I empirically investigate the application of self-defense protections along racial and gender lines. I also examine the causal impact of SYG adoption on the classification of homicides as self-defensive. Using regression analyses of the CDC’s National Violent Death Reporting System, I find strong evidence that racial and gender disparities lie in justifiability determinations. These determinations especially favor self-defense claims made by White men and women against Black male strangers, even in the absence of a preceding felony (e.g., robbery or sexual assault). Applying a difference-in-differences strategy, I find suggestive evidence that the passage of an SYG law increases the prospect that a homicide will be deemed justifiable, particularly in the absence of clear proof of self-defense. Taking together, the findings in this thesis indicate that the promise of self-protection is neither race-blind nor gender-neutral, and the expansion of legal self-defense protections may inadvertently broaden the authorized use of lethal violence.Applied Mathematic
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
A New Game of Jenga: A Query into the Contours of U.S. Anti-Terror Law Enforcement Preparedness 1932-1972
No full textOn September 20, 2001 in order to reassure to the American public, President
George W. Bush proclaimed, “our war on terror begins with Al-Qaeda but it does not end
here.”1 This declaration became to be known as the Global War on Terror and invited an
avalanche of political scholars and historians to uncover a new understanding of the
Middle East. But the story of how the United States has responded to terrorism has an
untold story, going back further to the edges of the Cold War.
The purpose of my thesis is to show how the federal government implemented
anti-terrorism policies by combating the infiltration of Russian communist influence prior
to the Second World War. It was during the edge of the Cold War in the 1950s that the
federal government used the very policies that it adopted to address what it considered
domestic terrorism in the 1960s. I argue that presidential desperation to address the
communist threat, coupled with the growth of the FBI’s extension into local law
enforcement created a curved impromptu approach to terrorism, geared towards domestic
threats while removing the focus on threats that originated internationally. My contention
is that the collaboration between President Franklin D. Roosevelt and FBI Director J.
Edgar Hoover expanded the purpose of the FBI to address the Russian communist threat
in the 1930s. The next step came with the success of the war’s conclusion in 1945, where
President Harry S. Truman initiated the National Security Act of 1947.
The policy manufactured approaches to national defense and takes us through a maze of
juxtapositions to combating elevating crimes rates. Together with the expansion of
federal law enforcement responsibilities and with the threat of communism, socialism and
fascism coming into its own borders, the United States would begin to define what we
refer now to as “terrorism.” National Defense policies in the late 1940s would have to be
redefined and inversely applied in order to uproot this growing problem.
There is a litany scholarship that has been dedicated to the military and
intelligence response of the dilemma of Cold War internationally, but little has been
discussed of how the United States sought to protect itself once it had already arrived
inside of its own borders. If we analyze the federal government’s discourse of policies
and discussions that have gone largely awry, we can see that the American public was left
exposed and vulnerable through a misguided path of blinding ideologies from its elected
polity.
My approach is unconventional and establishes a series of patterns that converge
into single road of symmetrical evidence. I purposely avoid seismic arguments that
involve the Second World War, the Great Depression and US. Diplomacy in the Middle
East primarily because they would distract from the greater point at hand. My argument
rests on the idea that the ability to combat terrorism in the United States originates in its
need to combat domestic terrorism and then rotates precipitously to combat international
terrorism. Ultimately, we can see a cyclical pattern of the US government is in a constant
flux preventing two types of terrorism under various circumstances. By focusing on the
examination of personal letters and documents from J. Edgar Hoover, Franklin D.
Roosevelt, official Congressional records, CIA declassified materials and historical
polling data so that we can see that many of these greater events created a new
unforeseen path to the events leading up to the tragedy of 9-11.Extension Studie
“It’s Eat or Be Eaten,” An Exploration of Cannibalism in Modern Japanese Manga
No full textOver the past two decades, Japanese manga has become a worldwide sensation. In that same timeframe, the medium has seen a surprising increase in depictions of cannibalism. What is most surprising, however, is that the protagonists are the cannibals, not the villains. This paper sets out to answer why Japan is producing so much art featuring cannibalism, when and why this trend began, why it is so prevalent in the medium of manga, specifically, and finally, why cannibalism is most often included as a method of increasing power. As there is no previous scholarly analysis of this trend, this analysis is largely grounded in the history and culture of Japan, its art, and its post-war social and economic situation. By tracking the development of manga this paper reads the medium itself as being created through the process of cultural anthropophagy, with its latent cannibalistic tendencies becoming more explicit following economic trouble. First with the bursting of the bubble economy in the early 1990s and then with the global recession of 2008. The alienation created by these troubles caused a reactionary nationalism which has manifested in a reclamation of cannibalism as a method of decolonial resistance. That these economic crises have disproportionately affected men is reflected in the appearance of so many of these cannibal characters being in Shōnen manga [manga aimed at young men] specifically, which is itself a hotbed of cannibalistic competition