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Computational and statistical genetic studies of human chromosome segregation and transmission
Get PDFErrors in chromosome segregation during human reproduction are remarkably common and generally detrimental to fitness. In this thesis, we leverage large-scale genomic data from human gametes and preimplantation embryos to investigate the fidelity of meiosis and mitosis. We first describe the development and application of a novel method, rhapsodi, to analyze low-coverage single-sperm sequencing data, revealing no evidence for transmission distortion in the male germline. Next, we use embryo development simulations and approximate Bayesian computation to estimate the rates of meiotic and mitotic error that best explain observed patterns of mosaicism and aneuploidy in blastocyst-stage embryos. Finally, we develop a method to leverage single nucleotide polymorphism microarray-based genotyping of DNA extracted from over 139,000 in vitro fertilized embryos from 22,850 sets of biological parents, conducting quantitative genetic analysis and identifying common genetic variants that modulate risk for meiotic aneuploidy. Together, these studies shed new light on the molecular and genetic methods that shape chromosome segregation, offering insights into the evolutionary dynamics of reproduction
EDUCATION KNOWS NO BOUNDARIES: TOWARD EQUITY FOR TRANSNATIONAL FAMILIES IN AMERICAN EDUCATION
No full textIn the United States, a growing number of transnational individuals maintain simultaneous cultural, economic, and social ties across two or more countries. For educational settings, this shift has led to a rising population of transnational families and teachers who mobilize multiple linguistic and cultural repertoires to navigate and communicate across national and institutional boundaries (Nash & Skerrett, 2025). Yet, monolingual educational policies continue to dominate American public schooling, even in diverse metropolitan areas, making both teaching and learning misaligned with the lived realities of students, families, and educators.
While existing research has explored how transnational students negotiate their identities in school, little attention has been paid to how other key stakeholders–families and teachers–experience and respond to monolingual schooling norms. This qualitative study investigates how these transnational stakeholders (re)construct their identities in relation to language ideologies and cultural expectations in K-12 education. Guided by Bronfenbrenner’s (1994) Ecological Systems Theory and Spencer’s (2008) Phenomenological Variant of Ecological Systems Theory, this study explores how system-level factors, from ideological frameworks and institutional policies to classroom practices, intersect to influence transnational school communities’ identity development, sense of belonging, and coping responses.
Data were collected through open-ended questionnaires and follow-up interviews with families and teachers across three metropolitan cities: Los Angeles, Miami, and New York City. Findings reveal both shared challenges and moments of resistance in navigating monolingual language policies. Ultimately, by centering the voices of transnational educators and families, this study aims to contribute to the development of more sustainable and equitable educational practices and policies that affirm transnational identities and help shift the culture of power in schools (Villenas, 2019)
Input-output based analysis of boundary layer flows: from transition inducing perturbations to wind turbine wake transport
Get PDFThis dissertation describes the use of input–output analysis techniques to study transitional boundary layer flows and transport in fully developed turbulence. In the context of transition, structured input-output analysis (SIOA) is used to
identify the types of perturbation structures most likely to induce transition. The structured formulation for a Blasius boundary layer is introduced and shown to reproduce results consistent with nonlinear optimal perturbation analysis, while maintaining the computational efficiency associated with linear methods.
The SIOA framework is then extended to the setting of asymptotic suction boundary layers (ASBL). Results demonstrate the expected reduction in the sensitivity of the flow to Tollmien–Schlichting waves. Analysis of the scaling behavior of the maximal structured response also produces results that align well with outcomes from direct numerical simulations and nonlinear optimal perturbation studies. Comparisons between results from the ASBL and the Blasius boundary layers highlight the effect of the uniform suction control on the characteristics of the optimal perturbations over a range of Reynolds numbers (as a proxy of the actuation strength).
The last section of the dissertation focuses on the use of an input-output framework to study the transport of fluctuating quantities in the velocity deficit behind a wind turbine (the wake). Here, the flow is linearized around a prescribed turbulent mean profile, and the ensuing linear operator is used to compute scale-dependent convective velocities for velocity and pressure fluctuations. The goal of this analysis is to examine differences in phase speeds across spatial flow scales that may be relevant to the propagation of wind turbine wakes. The results indicate that the velocity and vorticity fluctuations in the wake region convect with the mean velocity, validating the use of the local disk velocity in dynamic wake models. The pressure fluctuations transport deviates from the mean velocity in that small spanwise fluctuations travel at a higher convective velocity than the mean velocity, which may be of interest in more detailed analysis of wind farm flow physics
Impacts of State Abortion Restrictions on Mental Health and Healthcare
No full textThis dissertation investigates the impacts of state abortion restrictions enabled by the 2022 Supreme Court opinion Dobbs v. Jackson on mental health and healthcare. I study the effects of adopting a restriction on three domains: population mental health, care utilization, and the provider workforce.
In Chapter 1, I examine the impacts of state abortion bans that were established immediately after Dobbs on population-level symptoms of anxiety and depression. I find that compared to residents of the non-restrictive states, there was a greater worsening of symptoms among restrictive state residents, after compared to before the restriction was adopted. Across all models, females of reproductive age drove results. These findings reveal an important cost of restricting abortion, underscoring the need for robust availability of treatment services in restrictive states as their residents already face provider shortages and experience disproportionately high rates of unmet need.
In Chapter 2, I investigate whether utilization of outpatient mental health treatment services was impacted by state abortion restrictions. I find that monthly visits to outpatient mental health treatment facilities increased in restrictive states relative to non-restrictive states after versus before the restriction’s adoption. Consistent with Chapter 1, findings were driven primarily by female patients. Results suggest that restrictive state residents experiencing mental distress related to Dobbs may have been able to obtain care, however, effects may be transient as a majority of the outpatient mental health workforce is female and limitations on abortion historically have suppressed female labor force participation.
In Chapter 3, I study the effects of state abortion restrictions on the supply of new physicians to residency programs. I find that residency programs located in restrictive states were less able to fill their quotas for new physicians, entered the market with smaller quotas, and expanded hiring to less competitive applicants compared to programs in non-restrictive states pre-post restriction. Findings suggest that abortion restrictions had a contracting effect on the market for new physicians. These effects accrued primarily to ob-gyn and primary care programs, which is concerning as a significant portion of mental healthcare is delivered in primary care settings
THE ROLE OF THE GPI-ANCHOR CLEAVING ENZYMES GDE2 AND GDE3 IN SYNAPTIC FUNCTION
No full textNeurodegenerative diseases such as Alzheimer’s Disease (AD) and Amyotrophic Lateral Sclerosis/Frontotemporal Dementia (ALS/FTD) are characterized by progressive neuronal dysfunction, synaptic loss, and accumulation of pathological protein aggregates, leading to cognitive, behavioral, and motor impairments. Central to the pathology of these disorders is synaptic dysfunction, which disrupts neuronal communication and contributes to disease progression. As research increasingly highlights the importance of synaptic regulation and intercellular communication in maintaining brain health, novel molecular pathways involved in these processes need to be investigated. The Glycerophosphodiester Phosphodiesterase (GDE) family of proteins, specifically GDE2 and GDE3, have emerged as important regulators of neuronal and glial development and neuronal survival. GDE2 is expressed in neurons, among other cell types, and plays important roles in neurogenesis, synaptic protein maintenance and neuronal survival, with loss of function linked to key features of AD and ALS/FTD pathology. Meanwhile, GDE3, predominantly expressed in astrocytes and oligodendrocyte precursors, also regulates aspects of nervous system development and has recently been shown to release a distinct population of extracellular vesicles (EVs), although its impact on neuronal function remains unexplored.
Here, through a combination of behavioral, electrophysiological, and molecular approaches, I demonstrate that loss of GDE2 leads to behavioral deficits similar to those observed in AD and ALS/FTD models and causes abnormalities in hippocampal synaptic structure, function, and plasticity. I further show that GDE2 modulates N-methyl D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) via the PI3K-AKT-GSK3 (Phosphoinositide 3-Kinase – Protein Kinase B – Glycogen Synthase Kinase 3) signaling pathway. Lastly, I identify a distinct role for astrocytic GDE3 in early postnatal development, showing that EVs released by GDE3 are required for proper hippocampal postsynaptic function, likely through modulation of metabotropic glutamate receptor1/5 (mGluR1/5) signaling. Collectively, these findings highlight a previously unknown layer of synaptic and behavioral regulation by GDE proteins with potential implications for neurodegenerative diseases
Molecular and Microenvironmental drivers of pancreatic tumor progression: From early lesions to invasive phenotypes
Get PDFPancreatic neoplasia encompasses a continuum from precancerous lesions to invasive pancreatic ductal adenocarcinoma (PDAC), yet the molecular underpinnings that govern early neoplastic progression and invasion remain incompletely understood. This dissertation investigates two complementary mechanisms driving early pancreatic tumorigenesis and invasion: KLF4 hotspot mutations in intraductal papillary mucinous neoplasms (IPMNs) and hypoxia-mediated invasion in PDAC patient-derived organoids (PDOs).
In the first part of this work, we characterize the molecular consequences of KLF4 hotspot mutations found predominantly in low-grade IPMNs. Through RT-qPCR and proteomic profiling, we identify that KLF4-mutant lesions are correlated with suppressed mesenchymal markers and cytoskeletal remodeling, while enhancing ribosomal biogenesis and mitochondrial translation—suggesting a biosynthetically active but structurally restrained epithelial phenotype. These findings highlight the potential protective role of KLF4 mutations in maintaining epithelial identity and resisting invasive transformation, offering a unique perspective on early tumor evolution.
The second part of this dissertation explores the invasive behavior of PDAC PDOs under hypoxic conditions. We demonstrate that hypoxia significantly enhances invasion in an EMT-independent manner. Transcriptomic analysis reveals upregulation of hypoxia-responsive genes, including P4HA1, a collagen-modifying enzyme. Functional studies confirm that P4HA1 is regulated by HIF-1α and is both necessary and sufficient to drive invasion. Notably, P4HA1 overexpression increased invasion in normoxia, while knockdown impaired invasion specifically under hypoxic conditions. These findings establish P4HA1 as a critical mediator of hypoxia-induced invasion via ECM remodeling.
Together, this work broadens the paradigm of pancreatic tumor progression by elucidating EMT-independent mechanisms of neoplastic growth and invasion driven by genetic and microenvironmental factors. These insights offer promising avenues for therapeutic intervention in early and invasive pancreatic cancers
Testing Hubble Tension Systematics using Cepheids, Tip of the Red Giant Branch, and J-region Asymptotic Giant Branch
Get PDFThe Hubble Tension refers to a >5 σ discrepancy between local and cosmological measurements of the Hubble constant (H0) and suggests the possibility of undiscovered early-universe physics or underestimated systematics. Probing the Hubble Tension necessitates intense scrutiny of the Cepheid-based distance scale, which currently provides the strongest constraints on local measurements of H0. One powerful approach to crosscheck systematics in the Hubble Space Telescope (HST) Cepheid section of the distance ladder is to develop and improve independent routes to measure distances to the same set of galaxies and H0, such as those using the tip of the red giant branch (TRGB) and J-region asymptotic giant branch (JAGB), or by adding an independent anchor. I will present a sub-2% Cepheid distance to M31, which prepares an additional anchor galaxy that can be used to construct the distance ladder once a high-precision geometric detached eclipsing binary observation is feasible, as well as work improving standardization and calibration of the TRGB, including a 2D maximum likelihood formalism enabling Milky Way field star calibrations and contrast ratio standardization in the maser host NGC 4258. I will also present recent James Webb Space Telescope (JWST) TRGB distances to 8 hosts of 10 Type Ia supernovae (SNe Ia), later expanded to 25 hosts, which provides no evidence of a HST Cepheid systematic resolving the Hubble Tension, in addition to a H0 measurement using JWST observations of the JAGB with an expansion to 15 galaxies hosting 18 SNe Ia. While the JAGB remains promising as a tool that can crosscheck Cepheid systematics, non-uniform asymmetry in its luminosity function, caused in part by stellar contamination, presently limits the precision of this candle
NAVIGATING THE PATH TO CEO: BARRIERS AND FACILITATORS FOR BLACK EXECUTIVES IN FORTUNE 500 COMPANIES
No full textBlack or African American professionals encounter substantial obstacles in attaining chief executive officer (CEO) roles within Fortune 500 corporations, despite possessing leadership ambitions and qualifications comparable to their White peers (Livingston & Pearce, 2009; Roberts & Mayo, 2019; Ray, 2019). Disparities underscore deeply rooted systemic inequalities reinforced through structural, cultural, and interpersonal mechanisms, which impede career progression at every organizational level. Significant barriers include limited access to top profit-and-loss (P&L) roles, racial bias in social and professional interactions, and broader systemic inequalities that contribute to the racial wealth gap. As of 2022, Black families held just 15.8% of the median wealth of White households, highlighting the economic effects of structural barriers. Addressing disparities is essential for promoting social mobility and could boost the U.S. economy by $1.5 trillion by 2028 (Hewlett & Ihezie, 2022; McKinsey Institute, 2019). This study, grounded in social dominance theory (SDT; Sidanius & Pratto, 1999), explores how legitimizing myths, racialized organizational hierarchies, meritocratic myths, and ethnic prejudice sustain exclusionary practices in corporate leadership. This research uses multiple methods, including surveys on social dominance, racial attitudes, resilience, workplace aggression, interviews, and DEIA policy analysis, to explore (1) barriers and facilitators to advancement, (2) the effects of race-based hiring and promotion on careers and salary, and (3) coping and resilience strategies in racialized workplaces. Findings reveal mechanisms that sustain racial hierarchies and offer recommendations for organizational change to challenge dominance-oriented cultures
THE DENIALIST UNCONSCIOUS: CAPITAL ACCUMULATION AND REPRESSIVE NOVUMS IN SPECULATIVE MEDIA OF CLIMATE WRECKAGE
No full textThis dissertation challenges a conventional (often assumed or unspoken) critical presupposition that narrative representations of climate wreckage necessarily oppose the articulation, circulation, and reproduction of climate denial. Analyzing contemporary science fiction (sf) novels, films, and digital games published within a window roughly delimited by The Fifth Assessment Report of the United Nations Intergovernmental Panel on Climate Change (2014), this dissertation examines the construction and repressive functions of three sf figurations, called “novums”: the ark, arcology, and geoengineering. Mobilizing a theoretical apparatus that draws upon concepts and understandings from intellectual traditions including historical and dialectical materialism; Marxist theories of political-economy and cultural production; postcolonial critiques of The Enlightenment and modernity; psychoanalysis; aesthetic and critical theory; novel, film, and game studies; and contemporary climate science and discourse, this project demonstrates that various forms of climate denial continue to flourish not despite widespread narrativizations of climate wreckage but because of many of these representations, which mediate climate wreckage in ways that repress Real climate relations and thus (re)produce denial. This dissertation argues such texts constitute a material, powerful, and growing “denialist unconscious.” This dissertation aims to contribute a critical model of the imaginary and symbolic means through which climate narratives produce denial that perpetuates the economic, political, and social relations driving the climate crisis. Such a model can play a crucial role in exposing and negating mystifications which today misdirect great amounts of intellectual and physical labor towards ultimately accelerating the crisis
EXTENDED PRESERVATION OF KIDNEYS FOR TRANSPLANT AT SUBZERO TEMPERATURES USING BIOINSPIRED CRYOPROTECTANTS
No full textOn-demand replacement of organs and tissues could be a transformative solution to one of the most pressing challenges facing biomedical science today: the severe and global shortage of organs for transplantation. Yet one challenge remains: our inability to preserve organs during recovery, storage, and transport for extended durations. Organ-specific ischemia windows of 4-24 hours, and the reliance on the nearly 70-year-old practice of storing organs on wet ice at 4°C, severely limit the life-saving potential of organ transplantation, as organs continuously deteriorate with every additional hour of cold ischemia. Extending the preservation time of
organs from hours to multiple days could increase the availability of organs. Lowering the storage temperature to below freezing slows metabolism and theoretically could halt biological time. Previous attempts to store human-sized organs at subzero temperatures have failed to address the challenge of ice formation. Thus, the challenge emerges: How can we store whole organs at temperatures below their freezing points while avoiding damage from ice formation? This dissertation presents an alternative approach to extended preservation that is inspired by naturally occurring antifreeze proteins (AFPs), which enable certain species to survive at subzero temperatures. We introduce a new class of cryoprotective agent (CPA)—called peptoid CPA—and show that it can maintain organs in a non-frozen state at subzero temperatures for multiple days. We find that peptoid CPA at subzero temperatures, around -5°C, significantly extends the viable preservation time of donor organs to up to 5 days. We probe the pathophysiological mechanisms that enable subzero preservation to maintain tissue viability and function and provide biological evaluation of subzero preservation in an ex vivo machine perfusion and a large animal preclinical autotransplantation model. We demonstrate, for the first time, that subzero-preserved organs can restore renal function and support the life of nephrectomized animals for over 200 days. Finally, we demonstrate the real-world potential of this technology by successfully transporting a pig kidney preserved at subzero temperatures on a commercial flight across the Atlantic Ocean. The peptoid preservation solution provides a clinically translatable system that significantly extends organ preservation without modifying peri-transplant workflow