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Finessing to feed families and communities: understanding what it takes for East African women to navigate Boston’s food apartheid—a strengths-based approach
(2025) Gerges, Sara Nasser; Barnes, Linda
The literature on nutritional health outcomes tells us that marginalized people like Black people, immigrants and other foreign-born people, or poor people disproportionately face negative health outcomes. There is some literature that adds nuance to the discourse—particularly around the topic of the environment—discussing food deserts and swamps. However, the academic material does not include the experiences of the people involved. Black African immigrant women sit at the crosshairs of the academic health discussions on Black people and immigrants—and oftentimes poor people—but are never invited to the discussion table.
This study critiques the social and built environment of Boston to explore the effects the landscape has on food access and nutritional health. This research then takes a strengths-based approach and delves into how eight East African foreign-born women traverse an oppressive built environment to feed themselves and their families.
This study finds that not only do these women figure out creative and collaborative solutions to face manufactured food insecurity in a harmful built environment, but they also adapt to exclusionary US food stores and western popular views on food and nutritional health. Ultimately, they will find and create avenues of access to their food ways so everyone can eat.
Gender-diverse research collections: an exploration of assigned sex and gender in the New Mexico Decedent Image Database
(2025) Ehlers, Alysa; Tallman, Sean D.; Moore, Tara L.
Often, the first piece of information a forensic anthropologist estimates about a decedent is their assigned sex. This is an integral part of the biological profile which is frequently used to inform later decisions whilst estimating other information about the decedent, such as age at death or population affinity. Despite extensive research into performing an accurate assigned sex estimate, little to no research has been inclusive of gender diverse decedents. In particular, those who are intersex or transgender have historically been excluded from the reference populations used to create new methods. Given the heightened rates of violence and homicide against such gender diverse individuals, it is imperative that the existing assigned sex estimation methods be verified for use in such cases. In an attempt to address this gap in knowledge, this research explored the accuracy of assigned sex estimations applied to known intersex and presumed trans decedents present in the New Mexico Decedent Image Database (NMDID). As a modern research collection, the NMDID provides full-body computed tomography (CT) scans of over 15,000 decedents alongside secondary information, including sex, gender, and diagnosed medical conditions. Using this information, a total of 20 presumed gender diverse individuals were identified and used to verify the assigned sex estimation methods developed by Spradley and Jantz (2011), Walker (2008), Klales et al. (2012), and Jantz and Ousley (2005). By exporting the CT scans into Inobitec PRO, 3D surface renders of the relevant osseous elements of each decedent were used to perform assigned sex estimates. The results of each estimation were then compared to the known gender and sex of each decedent, as this would be the information provided to the police in a forensic case. In addition, the specific terminology used to classify each decedent in the NMDID was recorded and evaluated with regard to how supportive or derogatory it is. Ultimately, this research found that only three of the fifteen assigned sex estimation methods employed in this research were able to accurately identify the presumed gender diverse decedents. The only accurate methods were the formulae for the sacrum, os coxa, and calcaneus from Spradley and Jantz (2011). Of the terminology used in the NMDID, approximately half of the terms (n = 15) were neutral in nature, while the remaining terms (n = 16) were derogatory in nature. These results indicate two primary conclusions. The first is that the majority of current assigned sex estimation methods are not accurate when applied to gender diverse decedents. The second is that the terminology used by the NMDID to identify their gender diverse population is largely non-supportive and can lean derogatory.
Through Suzuki's eyes: Madama Butterfly in contemporary American production
(2026) Sheffield, Jeannette Lee; Eustis, Lynn
During the 2023-24 American operatic season, at least eight major U.S. companies staged Madama Butterfly, with four of these productions being brand new Asian-led productions. This concentration of work offers a unique lens through which to examine the mechanics of directorial intervention. By analyzing three of those four productions, looking at their specific models of intervention: textual revision (Phil Chan), interpretive reframing (Mo Zhou), and spectatorial reconfiguration (Matthew Ozawa), this study proposes a new framework for evaluating characterization and agency in canonical works.The dissertation draws upon qualitative interviews with these three directors and the Asian performers associated with their productions to document their perspectives on the opera. Furthermore, the study centers the character of Suzuki, who is traditionally categorized as a secondary or functional role. It utilizes a three-fold theoretical framework to articulate her dramatic weight: distributed expressive language, where her significance is embedded within the orchestration and temporal pacing of the score; interpretive labor, the embodied process through which performers animate her internal life; and the structural witness, a concept framing Suzuki as the opera’s “realist” and moral vantage point.
Additionally, the dissertation incorporates an analysis of demographic data from the Asian Opera Alliance to address broader issues of representation and “conditional inclusion” in the industry. Ultimately, this work argues that Suzuki is not a residual figure of the tragedy, but the character through whom its emotional and ethical consequences are most fully registered.
Acral lentiginous melanoma in skin of color: biology, diagnostic delay, and health disparities
(2025) Adrien Nuel, Alina; Offner, Gwynneth; Symes, Karen
Acral lentiginous melanoma is a rare subtype of melanoma that disproportionately affects darker-skinned people of color, primarily African Americans, Hispanic, and Asian populations. Lentiginous refers to the tumor’s radial growth phase before it starts invading the dermis. Compared to other melanomas, it seems to have a UV-independent path based on its development in sun-shielded locations. However, it is believed to have a positive correlation to trauma seeing as the soles of the feet, the most common manifestation sites, are weight bearing and are under the most mechanical stress. ALM lesions are often misdiagnosed and therefore not caught in time to be surgically removed This delay in diagnosis may be due to lack of awareness in both patients and clinicians, racial disparities, and the heterogeneity of the tumor. These factors essentially delay treatment and propagate the disparity in survival rates between darker skinned ethnic minorities and non-Hispanic, White populations. ALM is an understudied, aggressive disease that needs to be treated just as aggressively. Although there is ongoing research on viable treatment options for this disease, currently there are no effective interventions. However, closing these gaps and finding effective solutions requires a shift toward inclusive, multidisciplinary efforts.
The role of opioid signaling on HIV-1 infection in microglia
(2025) Skeete, Chelsey Alexandra; Gummuluru, Suryaram
The growing syndemic of HIV-1 and opioid use disorder (OUD) remains a public health concern. Injection drug use accounts for 12% of global HIV-1 transmissions, and 30% of people who inject drugs have HIV-1. People living with HIV-1 (PWH) and chronically using opioids have elevated risks of developing HIV-associated neurological disorders (HAND), characterized by chronic neuroinflammation and neurocognitive deficits. Microglia, resident brain macrophages, are the principal CNS HIV-1 reservoir that regulates neuroinflammation and are thought to contribute to HAND development. Microglia express μ opioid receptor, MOR, though the effects of opioids on HIV-1 replication and their immunomodulatory effects in microglia remain unclear. Our previous research has shown that HIV-1 intron-containing RNA (icRNA) expression infection of induced pluripotent stem cell-derived microglia (iMGs) triggers inflammatory responses. Thus, we evaluated the effects of morphine on MOR-expressing iMGs before and post-HIV-1 infection establishment. MOR activation upon morphine pretreatment before HIV-1 infection enhanced viral reverse transcription (RT), integration of intact proviruses, icRNA transcription, and p24Gag secretion in iMGs, which was blocked by naloxone treatment, a MOR antagonist. MOR activation also enhances Akt activation by phosphorylation in a PI3K-dependent manner and PI3K inhibitors suppress HIV-1 replication in microglia. In contrast, morphine treatment did not modulate HIV-1 infection in MOR-deficient macrophages. Interestingly, exogenous MOR expression in macrophages conferred morphine-mediated enhancement of HIV-1 RT, proviral establishment, icRNA, and p24Gag secretion, suggesting that MOR expression is essential for transducing morphine-modulating effects on HIV-1 replication. Importantly, morphine enhanced HIV-1 icRNA-induced IP-10, IL-8, and MCP-1 secretion in microglia, which was suppressed by a MOR antagonist, naloxone, and a PI3K inhibitor, wortmannin. These results indicate that MOR signaling and HIV-1 synergistically activate PI3K-Akt signaling in microglia, thereby exacerbating virus-induced inflammatory responses.
Bulk transcriptomic analysis of HIV-1-infected and morphine-treated microglia revealed activation of diverse neuroinflammatory pathways, though, surprisingly, there was minimal overlap between morphine- and HIV-infection-dependent pathway induction. For instance, morphine treatment skewed microglia phenotypes towards a disease-associated state with elevated expression of pathways associated with DNA damage response, phagocytosis, inflammation, and RNA metabolism, while HIV-infection was primarily associated with upregulation of inflammatory and type I interferon responses. Furthermore, morphine enhanced the expression of genes associated with Alzheimer’s disease and elevated inflammatory responses mediated the development of disease-associated microglia (DAM) phenotype. Enriched pathways upon morphine treatment that were associated with this dysfunctional microglia-like phenotype include hyper-cell adhesion, complement activation, cytoskeleton-associated cell protrusion, phagocytosis, and synaptic plasticity, which may contribute to loss of homeostatic functions in microglia and promote excessive phagocytosis-dependent synapse loss and cognitive decline. Follow-up proteomic analyses revealed that MOR antagonists, naloxone and CTOP, and OUD therapeutic, suboxone, suppressed inflammatory cytokine, IL-1β secretion while boosting type I interferon secretion HIV-1-infected microglia. Therefore, clinical opioid receptor antagonists can suppress inflammatory responses that further activate microglia and reduce the risk of microglia adopting a DAM-like phenotype.
Our findings show that opioid treatment before and after HIV-1 infection has differential effects on viral replication and innate immune activation. Morphine pretreatment before infection synergizes with the PI3K/Akt pathway to enhance early viral replication steps at reverse transcription, leading to enhanced immunostimulatory viral icRNA expression that triggers inflammatory responses. In contrast, morphine treatment during established HIV-1 infection enhanced both icRNA and msRNA expression along with inflammatory responses that induce a DAM phenotype with potential damaging effects on neuronal structure and synapse plasticity. Collectively, these findings highlight the mechanisms that contribute to increased risks of HAND development in PWH who chronically inject drugs and pave the way for future therapeutics. I propose that targeting MOR activation or the PI3K-Akt pathway could reduce HAND incidence and neuroinflammation in PWH using opioids.
Novel insights into gamma delta T cell heterogeneity revealed via investigation of inflammatory states driven by chronic viral infections and aging using next generation tools
(2025) Smith-Mahoney, Erika L.; Snyder-Cappione, Jennifer E.
In the normal aging population as well as in people living with anti-retroviral therapy (ART)-suppressed HIV infection (PWH), aberrant, chronic immune activation is associated with comorbidities and a shortened health span. Previous work in the Snyder-Cappione lab implicates gamma delta (𝛾δ) T cells, an unconventional, innate-like T cell population, as a driver of chronic inflammation with both ART-suppressed HIV infection and normal aging. To determine the distinct 𝛾δ T cell subsets that potentially contribute to chronic inflammation, this research takes advantage of technological advancements in fluorescent full spectrum flow cytometry coupled with innovative bioinformatics analysis strategies. First, we assessed the breadth and diversity of the circulating 𝛾δ T cell compartment, stratified by 𝛾δ T cell receptor chain usage (Vδ1, Vδ2, and V𝛾9), from individuals in our HIV and Aging cohort, comprised of younger (≤35 y/o) and older (≥50 y/o) PWH and uninfected counterparts (PWoH). Discrete subsets of Vδ1+ and Vδ2+ 𝛾δ T cells that were selectively higher or lower in PWH were elucidated. Specifically, populations of Vδ1+ terminally differentiated effector memory cells re-expressing CD45RA (‘EMRA’) distinguishable by CD45RA, CD8, CD38, and CD16, were present at higher frequencies in PWH compared to PWoH and were linked to plasma markers of inflammation. Comparisons based on age stratification revealed lower ‘naïve’ Vδ1+ in circulation in older individuals, regardless of HIV infection status. Conversely, Vδ2+ 𝛾δ T cells were phenotypically less diverse than Vδ1+ 𝛾δ T cells, were less abundant in the circulation of PWH than uninfected counterparts, and tracked with distinct inflammatory signatures. To our knowledge, our work is first to demonstrate the specific phenotypic subsets of Vδ1+ and Vδ2+ 𝛾δ T cells that are driving the HIV-associated alterations in the Vδ1:Vδ2 ratio.
Next, to uncover the driving forces behind higher frequencies of likely clonally expanded ‘EMRA’ Vδ1+ subsets in PWH and changes in the Vδ1:Vδ2 ratio, we assessed links between 𝛾δ T cells and T cell memory to herpesviruses. Most of the global adult population is latently infected with cytomegalovirus (CMV) and other herpesviruses with a significant proportion of PWH harboring >1 herpesvirus, yet herpesvirus pathogenesis has been underappreciated especially in the context of HIV co-infection. Importantly, clonal expansion of Vδ1+ and V𝛾9-V𝛾2+ 𝛾δ T cells has been documented in response to CMV viremia. Therefore, we hypothesized that ‘silent’ (asymptomatic) herpesvirus reactivation events may be playing a key role in the 𝛾δ T cell subset shifts and chronic inflammation found in older individuals and in PWH.
To address this hypothesis, we measured the frequencies of IFN-𝛾 secreting cells in peripheral blood in response to CMV, EBV, VZV, HHV-6, and HSV-1/2 peptide pools to quantify the magnitude of herpesvirus T cell memory as a footprint of one’s history of viremia and compared these responses with circulating 𝛾δ T cell signatures. Distinct subsets of ‘EMRA’ Vδ1+ and V𝛾9-Vδ2+ 𝛾δ T cells defined via expression of CD8, CD56, CD16, and CD57 selectively tracked with memory T cell responses to CMV among ART-suppressed aviremic PWH, but not uninfected individuals of our HIV and Aging cohort.
We also measured the cytokine secretion profile and T cell lineage defining transcription factor expression of circulating 𝛾δ T cells using additional flow cytometry panels. Findings revealed CD8+/- Vδ1+ ‘EMRA’ cells with variable expression of CD56 and CD57 produced granzyme B, IFN-𝛾, and TNF-𝜶, and were regulated by T-bet or GATA3. Assessment of Vδ2+ factions demonstrated that the majority of Vδ2+ produce both IFN-𝛾 and TNF-𝜶 and were regulated by T-bet or ROR𝛾T. In sum, these results illuminate distinct connections between herpesvirus-driven clonal expansion and differentiation of ‘adaptive’ 𝛾δ T cell effectors that we predict contribute to the progression and exacerbation of chronic inflammation with PWH and aging that shorten the health spans in these populations.
Overall, this dissertation work elucidates key 𝛾δ T cell subsets that likely contribute to the inflammatory responses in PWH and aging individuals and establishes 𝛾δ T cell connections to evidence of herpesvirus reactivation/viremia. These findings may help ultimately inform novel treatment strategies to ameliorate chronic and systemic inflammation.
Cutting ties with cancer: the therapeutic potential of disrupting protein-protein interactions to induce proteotoxic stress
(2025) Kemet, Chinyere Maat; Feng, Hui
Cancer cells exploit and rewire protein-protein interactions (PPIs) within essential cellular pathways to enable malignant transformation, uncontrolled proliferation, and resistance to cell death. This underscores the critical need to develop effective strategies that target key interactions within these pathways for the development of potent and selective inhibitors. Cancers are characterized by high levels of protein synthesis and are more susceptible to protein folding mistakes, making them rely on the activation of endoplasmic reticulum associated degradation (ERAD) to degrade these misfolded and unfolded proteins. Cancer cells leverage ERAD to maintain proteostasis and survive conditions with high cellular stress. ERAD is mediated by the interaction between the AAA-ATPase P97, ubiquitin fusion degradation protein 1 (UFD1) and nuclear protein localization protein 4 (NPL4) which together form a segregase, facilitating proteasome-mediated degradation by translocating misfolded and unfolded proteins from the ER to the cytosol. Multiple generations of P97 inhibitors have been developed to target the ATPase activity of the protein and exhibit potent preclinical anti-cancer efficacy, yet their feasibility for clinical applications remains uncertain, owing to the toxicities associated with ATP hydrolysis inhibition of P97. Here, we demonstrate that formation of the P97-UFD1-NPL4 interaction is critical for cancer cell survival while minimally required for normal cells. We developed short peptides as tools to disrupt the P97-UFD1 and UFD1-NPL4 interactions and found that targeting these interactions selectively induces a pro-apoptotic unfolded protein response (UPR) leading to cancer cell death in vitro and decreased tumor burden in vivo. Interestingly, targeting the P97-UFD1 interaction is more tolerated by zebrafish at the early embryonic development stage compared to targeting the UFD1-NPL4 heterodimer. Hence, pharmacological disruption of the P97-UFD1 interaction can serve as an alternative anticancer strategy to targeting the UPR, resulting in fewer toxicities than inhibiting the enzymatic activities of P97. In the pursuit of inhibitors targeting the P97-UFD1 interaction, we employed the Atomwise AtomNet® platform, which docked 12.5 million commercial compounds, and identified 87 compounds as potential hits. Through validation assays including biochemical and cell viability assays, as well as zebrafish xenograft assays, we narrowed down our focus to four small molecule candidates. We demonstrate that G02, H02, H08, and A’04 can disrupt the P97-UFD1 interaction leading to cancer cell death. These exciting findings pave the way for launching a new campaign of structure-activity studies and therapeutic testing for our promising small molecule hits, ushering development of selective and potent PPI inhibitors targeting the P97-UFD1-NPL4 interaction as future cancer drugs.
Wave of sleep in wakefulness: linking global CSF dynamics, local neural activity, and attentional states in the sleep-deprived human brain
(2025) Yang, Zinong; Lewis, Laura D.
People make countless decisions to maintain their well-being, sometimes sacrificing sleep, yet sleep itself remains a fundamental necessity for health. Acute sleep deprivation profoundly impairs both brain health and behavioral performance, leading to the accumulation of metabolic waste products in the brain and increasing the risk of critical human errors in high-stakes environments like medical practice and driving. Despite the substantial negative impact of sleep loss, effective countermeasures remain limited due to the lack of a complete understanding of the global and local brain changes driving both impaired waste clearance and cognitive dysfunction. This thesis addresses these questions by examining the effects of acute sleep deprivation on brain activity and how these neural changes influence cognitive performance. I employed fast functional magnetic resonance imaging (fMRI) with simultaneous electroencephalogram (EEG) and pupillometry to investigate how acute sleep deprivation alters cognitive, neural, and fluid dynamics in the human brain. First, I took a broad perspective, examining how large-scale neurophysiological changes influence sustained attention and fluid dynamics after sleep deprivation. The findings reveal that attentional failures during wakefulness after sleep deprivation are intricately linked to a series of coordinated brain-body changes, including neuronal shifts, pupil constriction, and cerebrospinal fluid (CSF) flow pulsations. I then narrowed my focus to the specific cortical networks that support sustained attention, showing that task-related attentional lapses are preceded by low-frequency, high-amplitude spontaneous hemodynamic activity seconds before stimulus onset. Overall, these results demonstrate that after sleep deprivation, modality‐general attentional deficits are characterized by global neural dynamics and fluid physiology, while modality‐specific attentional lapses are indexed by spontaneous, localized cortical hemodynamic activity, highlighting a complex, interconnected system governing attention regulation.
In vivo calcium imaging of accessory olfactory bulb mitral cells during social interactions
(2025) Byers, Spencer T.; Davison, Ian G.
There is a world of high-molecular-weight semiochemicals that permeate terrestrial environments, yet they lie completely beyond human olfactory perception. The mammalian vomeronasal system (VNS) is tuned specifically to this hidden class of non-volatile semiochemicals. These secreted cues convey a rich catalogue of social and ecological information—predator threat, mate availability, genetic relatedness, reproductive state, health, and hierarchical rank. Creating an accurate model of the world containing all of this information is critical for animals to execute appropriate social behaviors. While ex vivo and anesthetized preparations have shown that accessory olfactory bulb (AOB) mitral cells (AMCs) encode an array of conspecific traits, we still know little about how those codes arise when an animal roams through the rich, natural chemosensory tapestry of a social scene, or how the real-time dynamics of this sensory system relate to the social behaviors that they influence. The aim of this dissertation is to resolve some of the gaps in our understanding of sensory encoding in AOB of awake behaving mice, and the behavioral relevance of these signals.Leveraging advances in miniscope calcium imaging of deep brain structures, we were able to visualize the activity of hundreds of glomeruli and AMCs as subjects freely investigated conspecifics. Large-scale recordings revealed that AOB ensembles represent different biological traits along a continuum—from broadly distributed to relatively sparse population codes. Population activity reliably differentiated the sex and strain of a stimulus mouse, while the specific body region being contacted was less robustly encoded. Although the code was robust on average, the exact set of responsive neurons varied from one investigation to the next, uncovering marked trial-to-trial heterogeneity that appears to limit the sensory information available on individual nasal contact encounters.
During dyadic, unrestrained encounters, the AOB activity still carried clear information about the partner conspecific’s sex. AOB ensemble activity reshaped continuously during the encounter, suggesting integration of social context over extended periods rather than a one-to-one response to each contact.
Years of lesion and knock-out studies have left an ambiguous picture of how essential AOB output is for inter–male aggression: constitutive Trpc2 or Kirrel3 deletions and peri-pubertal VNO ablation nearly abolish fighting, and aggression is promoted by select VNO sensory inputs, yet adult VNO lesions or interneuron silencing in the AOB have more subtle and complex effects. Using our miniscope-based approach, we could—for the first time—watch AOB population dynamics in residents during the entire resident–intruder sequence, from initial investigation through attack.
We found that castrated males, a stimulus class known to elicit attenuated aggression compared to intact-male counterparts, are encoded as a distinct sensory category in the AOB. Crucially, ensemble activity did not show a stereotyped burst prior to attack initiation, suggesting that AOB activations do not themselves elicit attacks. Instead, the composition of active cells during the investigation phase diverged systematically between intact males and non-males, implying that the AOB biases the resident toward—or away from—an aggressive state rather than triggering individual attacks. A generalized-linear-model analysis suggests that longer-term accumulation of sensory evidence encoded by these ensembles better predicts the timing of the internal switch into aggression, outlining a mechanism by which AOB output can bias downstream networks modulating the animal’s motivational state rather than directly triggering overt actions.
In summary, this dissertation reports the first large-scale recordings of AOB population activity during self-guided exploration of complex chemosensory scenes and throughout inter-male aggression, a behavior thought to be mediated by the VNS. The findings refine our understanding of naturalistic sensory encoding in awake behaving mice and suggest that long-timescale integration of AOB signals biases the resident’s internal state during aggression rather than directly initiating attacks.
Circadian regulation of fasting-induced cellular resilience
(2025) Colella, Cristianna; Symes, Karen
Cellular resilience, the capacity to maintain homeostasis against challenge, is a defining feature of healthspan. This capacity is influenced by both the nature of stressors and the timing of the organism's response. The circadian clock, which coordinates gene expression across a 24-hour cycle, preemptively activates stress response programs in anticipation of recurring physiological challenges, of which nutrient unavailability is a cue. Fasting during specific time windows that coincide with the body's endogenous clock mechanisms imposes a controlled, predictable metabolic challenge that activates these protective pathways.This thesis examines the mechanistic interdependence between circadian rhythms and fasting responses, focusing on their point of integration, the NAD+-sirtuin axis, which translates nutrient availability signals into resilience outputs. Through analysis of circadian NAD+ oscillations, their parallel sirtuin-mediated transcriptional control pathways, and time-restricted feeding paradigms, this work demonstrates how temporal alignment of fasting with endogenous rhythms amplifies cellular resilience.