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Scalable Biomarkers for Psychiatry via Digital Phenotyping, Sensorimotor Modeling, and Neuroimaging
No full textPsychiatric illnesses present a formidable challenge due to their heterogeneity, subjective diagnosis, and limited objective biomarkers. As the field moves toward precision psychiatry, there is a pressing need to identify scalable, mechanistically grounded, and behaviorally relevant biomarkers that can be deployed across diverse populations. This dissertation addresses that need by integrating methods from digital phenotyping, sensorimotor modeling, and neuroimaging to uncover new avenues for scalable psychiatric biomarker development.
In Chapter 1, we address clinical heterogeneity in schizophrenia through digital phenotyping using smartphone-derived ecological momentary assessments (EMA) and passive sensor data. By employing a rigorous data imputation and clustering pipeline across an international cohort, we identify three data-driven subtypes that show distinct symptomatology and functional profiles. These clusters correspond to different symptom domains (e.g., affective vs. non-affective presentations) and reveal meaningful clinical correlations that may inform personalized interventions.
Chapter 2 focuses on scalable sleep estimation using smartphone sensors, tackling the limitations of traditional actigraphy and self-report methods. We introduce a Bayesian hidden Markov model that estimates sleep states using screen-state and accelerometer data alone, enabling continuous sleep tracking without the need for wearables. We validate the model using simulated datasets and self-reported EMA surveys from multiple cohorts, highlighting its robustness and potential utility in psychiatric contexts, particularly where sleep variability is a key feature.
In Chapter 3, we explore the cognitive architectures underlying motor learning through the lens of explicit and implicit adaptation. Using carefully designed behavioral experiments, we disentangle the feedback-dependent dynamics of reward-based and error-based learning. Our findings show that reward feedback engages explicit strategies and indirectly drives implicit learning through a serial pathway, whereas error feedback drives both systems in parallel. These architectures provide a novel mechanistic framework for understanding motor learning deficits in psychiatric populations. A meta-analysis of schizophrenia studies reveals impairments in both implicit recalibration and explicit strategy use, suggesting dysfunction in cerebellar and prefrontal systems and highlighting motor adaptation as a candidate biomarker.
Finally, Chapter 4 investigates the impact of chronic adolescent THC exposure on large-scale brain network connectivity in nonhuman primates. Using resting-state functional MRI and dual regression analysis, we uncover non-linear, dose-dependent effects on the default mode, salience, and central executive networks. These alterations, especially within the central executive network, persist even after THC discontinuation and implicate adolescent exposure in long-lasting network reconfiguration. These findings underscore the utility of translational neuroimaging models in probing the neurodevelopmental origins of psychiatric vulnerability.
Together, this dissertation offers a multifaceted yet integrative approach to psychiatric biomarker discovery. By leveraging scalable technologies and biologically grounded frameworks, we advance the potential for objective, continuous, and individualized assessment tools in psychiatry. The combined insights from digital phenotyping, sleep modeling, motor learning, and functional connectivity provide a robust foundation for future biomarker-based interventions and personalized mental health care.Engineering and Applied Sciences - Engineering Science
Murder City: Crime, Crisis, and Community in Post-Industrial America
No full textThis dissertation explores the relationship between crime control and community activism in Detroit, Michigan from the early 1970s to the mid-1990s. It does so by investigating how city officials and residents thought about, debated, and acted against the most pressing symptoms of the late twentieth century urban crisis. I ask how anti-crime organizing emerged and evolved, and how that evolution shaped and was shaped by the national and local politics of crime-fighting. How urban residents responded to the problems they faced reveals the ways in which metropolitan life and politics transformed during the last three decades of the century and how the politics of crime control was emblematic of that transformation.
Struggles over safety and security were part of a nexus of ideas, policies, and social movements around assessing and improving urban life in a period of punitive state-building and social crisis. This dissertation demonstrates that anti-crime activism became a significant force in urban crime control. A neighborhood-based struggle for safety and security took place, resulting in the formation of coalitions of urban residents who demanded and sought solutions to escalating levels of violence and disorder. Anti-crime activists, the organizations they created, and the government officials they wrestled with for power played a crucial role in the public-private partnership-driven shape of crime control and urban governance that came to dominate American cities during the late twentieth century. In tracking the history of urban anti-crime activism, this dissertation reveals how police reform and crime control became one of the primary battlegrounds for politics, protest, and policymaking in American cities during the late twentieth century.Histor
Anatomical and Functional Characterization of Gastrointestinal to Spinal Cord Circuits
No full textViscerosensory functions such as those governing the gastrointestinal (GI) tract
are essential for maintaining homeostasis, regulating appetite, and generating the
sensory experiences that shape daily life. Sensory circuits linking the colon to dorsal
root ganglia (DRG) neurons and spinal cord are required to detect and transmit
mechanical and chemical signals from the gut to the central nervous system, enabling
appropriate physiological and behavioral responses. Despite their importance, these
colon-DRG-spinal cord pathways remain remarkably understudied, leaving fundamental
questions about how internal sensory signals are encoded unanswered. Here, we
characterized the anatomical and functional organization of colon-DRG-spinal cord
circuits and investigated how spinal cord neurons process signals from the colon
compared to the skin in normal and disease states.
Using genetic labeling strategies targeting colon-innervating DRG subtypes, we
identified four distinct central morphologies that include basket-like, simple, peri-central,
and midline-crossing arbor subtypes, which are distinct from the more tufted arbor
morphology of skin-innervating DRG neurons. In addition, we discovered a unique
subset of Calca+ colon-innervating neurons that project through the dorsal columns and
terminate in and around the area postrema and nucleus of the tractus solitarius,
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revealing a previously unknown direct pathway for colon-derived sensory information to
the brainstem.
To assess how sensory information from the colon is processed in the spinal
cord, we developed an in vivo electrophysiology recording preparation to assess spinal
cord neuron responses to colon or skin stimulation. Surprisingly, the majority of colon-
distension-responsive spinal neurons also responded to innocuous skin stroking
(‘convergent neurons’). Convergent neurons displayed graded responses to innocuous
and noxious colon distension, while colon-stimulus-responsive-only neurons were
activated primarily by noxious distension stimuli. Optogenetic activation of colon- and
skin-innervating DRG neuron subtypes revealed that convergent neurons exhibited
higher peak firing rates and higher response correlations to skin-directed than colon-
directed stimuli, suggesting differential integration of visceral versus somatic inputs.
Finally, in a mouse model of colitis, we find that convergent neurons exhibited
heightened responses to both colon and skin stimulation, including prolonged excitation
following innocuous skin touch, while colon-stimulus-responsive-only and skin-stimulus-
responsive-only neurons were unaffected by DSS treatment. These data indicate that
convergent spinal cord neurons may contribute to cross-sensitization and persistent
pain following GI inflammation.
Taken together, our findings reveal distinct morphological and functional features
of colon-innervating DRG neurons and highlight the extensive convergence of visceral
and somatic inputs in the spinal cord, with implications for understanding chronic pain in
GI disorders.Biological and Biomedical Science
Decoding DUB regulation in Golgi reassembly and protein degradation
No full textThe ubiquitin proteasome system (UPS) plays a critical role in maintaining protein homeostasis in cells – regulating both protein synthesis and protein degradation. Embedded in the UPS are proteins that (1) add ubiquitin enabling different signals, (2) remove ubiquitin signals allowing for substrate rescue and (3) recognize poly-ubiquitin signals for subsequent proteasomal degradation. Targeting different components of the UPS is of high interest for drug discovery in hopes to uncover novel therapeutic targets for regulating protein homeostasis for a wide range of diseases. My thesis work investigates interactions of deubiquitylating enzymes (DUBs) to various players in the UPS to explore the possibility of targeting specific DUBs, with in-house DUB inhibitors, to regulate substrate fate. In Chapter 2, I utilized structural biology, biochemistry and cellular biology to elucidate the interaction between VCPIP1, a DUB of interest, with VCP, a key player in the UPS, and p47, a VCP adaptor protein, in the context of Golgi reassembly. In Chapter 3, I employed biochemistry to understand the function of VCPIP1 at the C-terminal end of VCP in the context of the UPS. In the presence of a poly-ubiquitylated substrate, we used fluorescence-based assays and SDS-PAGE gels to assess the effect of VCPIP1 domain truncations as well as VCPIP1 and p97 inhibitors on VCP and VCPIP1 function. We provide initial structural analysis of a substrate-engaged VCP-VCPIP1C219A-UN complex. In Chapter 4, I applied mass spectrometry proteomics and structural biology to characterize the structural features of USP family of DUBs, specifically USP7, USP25 and USP48, and explored their interactome to discover unknown binding partners for the DUBs. The multi-faceted discoveries from my thesis work provide new structural and functional understanding of a few DUBs of interest using cryo-EM, biochemistry, cellular biology and proteomics. Taken together, this unveiled new binding regions for inhibitor development demonstrated by the newly characterized bivalent interaction of VCPIP1 to VCP and/or revealed novel interactions with binding partners between DUBs and E3 ligases observed in the proteomics data that can be leveraged for targeted protein degradation.Biological and Biomedical Science
A Multi-Wavelength Perspective of Volatiles Across Protoplanetary Disk Regions
No full textThis thesis investigates the spatial distribution, excitation, and chemical evolution of volatiles in protoplanetary disks through a combination of submillimeter interferometry and mid-infrared spectroscopy. Leveraging high-resolution ALMA observations and recent JWST-MIRI data, we characterize how the molecular composition varies across disk regions and with disk properties. The work aims to constrain both physical conditions and chemical processes relevant to planet formation, with particular focus on deuterium fractionation, snowline physics and chemistry, and the role of pebble drift in enriching inner disk gas.
In Chapter 2 we carry out multi-line ALMA observations of deuterated organics in TW Hya, demonstrating that \textit{in-situ} deuterium fractionation occurs near the CO snow-surface, consistent with H2D+-driven chemistry. In Chapter 3, we perform JWST-MIRI spectroscopy of the AS 209 disk, revealing rich water and organic emission, with notable temporal variability relative to archival Spitzer data. In Chapter 4, we develop a retrieval framework for inferring radial water vapor distributions from unresolved JWST spectra, finding that the observable cold water masses anti-correlate with disk size, likely due to efficient icy pebble drift. In Chapter 5, we analyze the transition disk GM Aur with JWST, where volatile depletion in the inner-disk is accompanied by strong OH emission from photodissociation, pointing to irradiation-driven chemical evolution. Finally, in Chapter 6 we extend the prior analyses to a 40-disk sample from the IDECO JWST survey, confirming and revealing new links between disk structure, stellar properties, and water vapor emission. Together, these studies provide new empirical constraints on how volatile chemistry in disks is actively reshaped by local thermodynamic conditions, dynamics, and stellar irradiation.Astronom
Essays on the Effects of Labor Market Change on Workers, Students, and Families
No full textThis dissertation contains a series of essays that explore various ways in which labor market change affects people in their roles as workers, students, and household members.
The first chapter studies how workers are affected by job displacement. Layoffs are a recurring feature of a dynamic economy. Prior research has used administrative records and survey data to document that layoffs impose large adjustment costs on displaced workers, and that these costs vary depending on labor market conditions around the time of the layoff. Compared to those established data sources, online resume data have the potential to provide richer and more timely insight into these adjustment costs for a larger number of workers. This chapter explores that potential. Based on the full list of advance notices of mass layoffs issued in California between 2014 and 2024, I identify establishments and workers who were exposed to one of these mass layoffs among a sample of 62 million LinkedIn profiles. Layoff events have a large effect on establishment size as measured in the LinkedIn data. I characterize the job transitions of workers who leave affected establishments around the layoff event along a rich set of measures, and estimate how their job transitions vary by occupational labor market size and the amount of competing labor supply at the time of the layoff. Workers laid off into less favorable labor market conditions are less likely to make an upward career transition, more likely to move to a new metro area, and more likely to enroll in a degree or certification program in response to the layoff.
The second chapter, co-authored with Joshua Goodman, studies how higher education enrollment in the United States responds to labor market conditions. Declining college enrollments over the past 15 years have triggered questions about the health of the postsecondary sector. Using institution-level data, we make four points. First, such declines are driven not by the four-year sector but by two-year community colleges, which have apparently shrunk by over 30% since the peak of the Great Recession. Second, over one-third of this apparent decline is an artifact of some community colleges being reclassified as offering four-year degrees. Third, pre-Great Recession data shows a 1 percentage point increase in the local unemployment rate increases first-time community college enrollment by 2 percent, suggesting many students are on the margin between community college and job opportunities. For-profit college enrollments are similarly countercyclical, while public and private four-year college enrollments appear acyclical. Our estimates suggest that strengthening labor markets explain about 60% of the post-Great Recession decline in first-time community college enrollment. Fourth, students whose enrollment decisions are most sensitive to labor market conditions appear unlikely to have completed a degree. Though declining community college enrollments are a challenge for postsecondary institutions, it is less clear whether they signal a problem for students on the margin of enrollment.
Finally, the third chapter, co-authored with Clara Chambers and Benjamin Goldman, studies how gender disparities in labor market and education outcomes are affecting marriage and family formation in the United States. Over the past half-century, U.S. four-year colleges have shifted from enrolling mostly men to enrolling mostly women, while the economic position of non-college men has weakened markedly. We examine how these changes correspond with the evolving structure of marriage markets across cohorts and places. As college men have become increasingly scarce, college women have maintained stable marriage rates by marrying high-earning non-college men. This shift—combined with the broader economic decline of non-college men—has sharply reduced the pool of economically stable partners available to non-college women: the share of non-college men who earn above the national median and are not married to college women has fallen by more than 50%. Cross-area evidence shows that education gaps in marriage are smaller where non-college men face lower rates of joblessness and incarceration. Taken together, the evidence suggests that deteriorating outcomes for men have primarily undermined the marriage prospects of non-college women.Public Polic
Essays on Max Weber and Friedrich Nietzsche
No full textThis dissertation compares two diagnoses of problems facing Europe in the late nineteenth and early twentieth centuries, the first offered by Max Weber and the second by Friedrich Nietzsche. The dissertation is composed of three papers. The first paper asks why Weber locates a threat to Germany in the growing entrenchment of a “bureaucratic caste.” Weber argues that the increasing complexity of modern technology and social organization requires a deep division of labor and specialization which insulate the state bureaucracy from democratic control. To counter this and promote “co-rule” among citizens, he advocates for a strong parliament to keep the public informed about the bureaucracy which has such extraordinary power over its daily life. But Weber also argues for a national “plebiscitary leader” elected directly by the people rather than by parliament. Only such a figure, backed by the “trust of the masses,” would have the power to wrestle the bureaucracy into submission and thereby exert a kind of democratic control over it. He attempts to strike a delicate balance between a plebiscitary leader sufficiently powerful for this task and a parliament sufficiently powerful to check the “plebiscitary dictator” and prevent a slide into “Caesarism.” Weber insists on equal suffrage, excoriating proposals which would deny soldiers returning from the First World War a say in the affairs of the state whose existence they have preserved. His defense of equal suffrage is based not on natural rights but on a sense of “political decency” toward the returning soldiers and on reasons of national unity, especially that required for future military mobilization. In this paper I argue that it would be a mistake to understand Weber as paving the way to a kind of proto-fascism, as some have argued.
The second paper contrasts Weber and Nietzsche by comparing their attitudes toward “national political ambition.” Weber insists that participation in great power politics both requires and promotes the “political maturity” of the citizens by confronting them with weighty decisions of international commerce, diplomacy, war, and peace. Only a nation in which citizens are co-rulers rather than subjects of a bureaucratic caste has the right to participate in world politics, and in turn this participation offers an essential political education in citizen co-rule. Because of its specific historical circumstances leading up to the First World War, including its position as a Machtstaat (power-state), Germany has a “tragic” duty to defend the Germanic peoples of central and northern Europe against English and Russian encroachment. This reflects Weber’s view that politics should aim to preserve a distinct national character and should resist universal political moralities such as utilitarianism. He understands Germany’s “fate” to require the sacrifice of “other cultural possibilities,” including artistic values, as the nation directs its most talented individuals into politics and war. The paper here turns to Nietzsche, who agrees with Weber that the pursuit of national power politics will produce a culture antithetical to the creation of great art and philosophy. But Nietzsche disagrees with Weber’s conclusion, warning that the “political blossoming of a people almost inevitably brings with it a spiritual impoverishment and exhaustion.” He asks whether the “coarse and gaudy flower of the nation” is worth the sacrifice of the nation’s “more noble, more delicate, more spiritual plants and growths.” The remainder of the paper explores Nietzsche’s hostility toward national political ambition and public life more broadly, with particular attention to his understanding of the role of solitude in the creation of art and philosophy. It attempts to say why Nietzsche thinks “anything great in the cultural sense is apolitical, even anti-political.”
The third paper explores why Nietzsche thinks solitude is important here, and why he suspects that modern moral psychology risks insisting that “all solitude is guilt.” The paper pays particular attention to Nietzsche’s understanding of the genesis of guilt in modern morality, especially its evolution within Christianity under the concept of “sin.” The dissertation concludes by offering reflections on the supposed connection between Nietzsche and twentieth-century fascism. My view is that it would be misguided to understand Nietzsche as preparing the ground for Nazism, primarily due to his hostility to the “petty provincialism” of nationalism and to any form of mass politics. But it would be equally misguided to use his ideas for egalitarian or democratic ends, and here the contrast with Weber, who defends a kind of democratic nationalism, is most stark.Governmen
Enteric neuro-immune interactions in host defense
No full textThe enteric nervous system (ENS) can profoundly influence gut immune cell function and the inflammatory response. However, despite the numerous examples of ENS-derived neuropeptides modulating immune cell function, our understanding of how enteric neurons directly sense inflammatory cues produced during infection is considerably lacking. Therefore, a thorough characterization of the mediators capable of being sensed by enteric neurons is critical to understanding enteric neuron function and dysfunction in gastrointestinal disease.
To survey the expression of immune-related receptors on enteric neurons, we integrated three publicly available single-cell RNA-sequencing (scRNA-seq) datasets profiling enteric neurons of the small intestine, finding that the single cluster of primary enteric sensory neurons (PSNs) co-expressing Nmu and Calcb, encoding the immunomodulatory neuropeptides NMU and CGRPβ, was highly enriched in genes encoding the receptor for the type 2 cytokines IL-4 and IL-13 and its essential signaling components. Using in vitro enteric neuro-glial cultures and in vivo mouse models of PSN-specific Il13ra1 deletion, we discovered that direct PSN recognition of IL-4 and IL-13 is sufficient to upregulate NMU and CGRPβ expression. Furthermore, deletion of Il13ra1 in PSNs impaired host defense to the gastrointestinal helminth H. polygyrus and significantly diminished duodenal PSN neuropeptide expression, PSN innervation to the villi, and PSN abundance in the myenteric plexus.
Moreover, PSN Il13ra1 deletion blunted anti-helminth type 2 immune responses in a site-specific manner, reducing Il5 expression in muscularis ILC2s, eosinophil recruitment to the muscularis, and muscularis macrophage (MMφ) expression of genes involved in tissue repair and anti-helminthic immunity, like Arg1/arginase-1. Importantly, co-administration of NMU23 and CGRPβ rescued helminth clearance deficits and restored type 2 immunity and MMφ arginase-1 expression.
In summary, our work illustrates the importance of direct cytokine sensing by PSNs during gastrointestinal helminth infection and delineates a mechanism of site-specific anti-helminth immunity in the muscularis externa. We further define how the highly correlated NMU and CGRPβ expression in PSNs promotes appropriate muscularis-specific anti-helminth immunity while buffering inflammatory tissue-damage, highlighting the essential bi-directional neuro-immune crosstalk regulating intestinal type 2 inflammation.Immunolog
scissor theories: biology, engineering, art
No full textMost beautiful things we encounter in life (Taylor expansions, Jean Genet’s "Un Captif Amoureux", a California burrito, etc.) do not consist of a lattice of scissor mechanisms carefully interconnected to enable global mechanical deformations. This dissertation studies three objects which do.
More formally, this dissertation examines the geometry, mechanics, and dynamics of systems which share the common geometric motif of a two-bar linkage – what we will call a scissor mechanism. First, we discuss the tail of the T4 bacteriophage – the contractile injection system – and demonstrate a coarse grained analytical model which allows us to treat the geometry and energetics of its contraction process. Next, we turn to the morphology of woven materials, and indicate the surprising geometric complexity of this quotidian regime. Finally, we introduce a class of metamaterials assembled from lattices of scissor mechanisms and trace a mathematical analogy to origami and kirigami which in turn inspires their name: “hasamigami”.Physic
Criticality, fractionalization, and superconductivity in two-dimensional quantum materials.
No full textEmergence is a foundational concept in modern condensed matter physics, capturing the idea that interactions between many degrees of freedom can give rise to phenomena that have no analog at the level of individual constituents. Superconductivity stands as one of the most celebrated exam- ples of emergence, where electronic correlations give rise to a macroscopically observable coherent quantum-mechanical state. More recent developments in the field include the study of emergent gauge theories, which describe the highly entangled states of matter that can appear in frustrated and strongly interacting systems. As increasingly exotic phases of matter are discovered, a deeper understanding of how strong correlations give rise to these phases and the transitions between them becomes essential.
In this dissertation, we will explore the concept of emergence in the context of two-dimensional quantum materials. In the first part, we will discuss the exotic phenomenology of high-temperature cuprate superconductors and present a theory for a fractionalized parent state of superconductivity. We will describe how such a parent state can account for several experimental observations made in both the superconducting and charge-ordered phases. We will describe how our normal state can be understood as an emergent gauge theory, with possible applications to the study of deconfined critical points. Furthermore, we will study the critical properties of out theory through a renormal- izationgroupN1 analysis.
We will also explore the strange metallic phase of the cuprate superconductors, presenting a study at large M of a simplified, zero-dimensional model that captures the spin glass phase observed at low doping, the Planckian metal phase near criticality, and the Fermi-liquid-like phase at high doping. Additionally, we will examine the 1/M corrections demonstrate that they always lead to spin glass ordering at low doping.
In the final part of this dissertation, we will discuss several examples of superconducting and in- sulating phases observed in moiré materials. First, we will investigate the possibility of deconfined criticality in twisted bilayer graphene and identify the potential superconducting pairing states com- patible with a direct second-order transition between the superconductor and insulator. Next, we will present a mean-field analysis of insulating and superconducting instabilities in several stacked van der Waals materials. We will further discuss the consequences of inter-band coherence on ob- servables in the superconducting state.Physic