University of Illinois at Chicago
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3D Optical Tissue Microscopy Towards Spatial Cell Proteomics
No full textSpatial proteomics is an emerging field that enables the study of protein expression and organization within complex tissue environments. This dissertation presented two novel spatial proteomics methodologies to advance tissue-scale and cell-type-specific protein profiling through 3D optical microscopy.
The first approach integrated light-sheet fluorescence microscopy (LSFM) and confocal laser scanning microscopy (CLSM) into a multi-scale imaging pipeline. A novel tissue-clearing and rehydration method was developed to enhance tissue transparency and preserve antigenicity, allowing for sequential imaging at organ-, tissue-, and cellular-level resolutions. This workflow was applied to an asthma mouse model, revealing distinct spatial distributions of immune cell infiltrates in the lung and their relationship to anatomical structures such as airways and blood vessels.
The second approach introduced a tissue-niche-based and cell-type-selective proteomics strategy (Niche&CellType-SP). This method employed microscopic photobleaching to encode spatial information into single cells within thick tissue slices. Labeled cells are subsequently dissociated, sorted via flow cytometry, and analyzed through liquid chromatography-mass spectrometry (LC-MS) for deep proteomic profiling. This technique was validated in mouse models of systemic inflammation and peripheral T cell lymphoma (PTCL), identifying distinct dendritic cell subpopulations and exploring T cell-macrophage interactions.
The workflow was optimized for human tumor specimens to translate these methods into clinical applications. Future improvements will focus on incorporating antigen retrieval for formalin-fixed tissues, enhancing tissue dissociation efficiency, immune cell enrichment, and preserving fluorescence and antibody bonding to facilitate the translation to biomarker discovery and personalized medicine in clinics.
This dissertation advances the field of spatial proteomics by introducing two innovative optical microscopy tools that enable multi-resolution observation, cell-type-specific protein mapping, and comprehensive protein profiling. These methodologies offer valuable insights into identifying novel immune cell subtypes, screening protein biomarkers as potential therapeutic targets, investigating macrophage influence on tumor T-cell progression, and exploring ECM-driven macrophage differentiation in tumors. Together, these approaches lay the foundation for future biomedical research, immunology, and translational medicine applications
Inflammation as a Potential Mechanism of Lung Cancer Disparities in African Americans
No full textLung cancer is the leading cause of cancer-related mortality in the United States. Despite a gradual decline in overall lung cancer cases, there haven’t been similar improvements in the disparities that exist in lung cancer incidence, mortality and survival. African Americans experience a disparately high incidence of lung cancer independent of tobacco and environmental exposures. One potential explanation is that within African Americans, persisting inflammation, known to promote tumor progression, may be overactivated through a variety of ancestral and environmental factors, resulting in a pro-tumorigenic microenvironment consisting of aberrantly polarized myeloid cells.
In this study, we hypothesize that the racial disparities observed in lung adenocarcinoma are potentially linked to a higher proportion of pro-tumorigenic inflammatory myeloid cells within the microenvironment that promotes premalignant lesion progression to invasive carcinoma. To conduct the analysis, single-cell RNA sequencing data from tumor and adjacent normal tissues representing pre-invasive lesions were evaluated for two African American patients using the Scanpy workflow. To study the broad impact of inflammation on the tumor microenvironment within the pre-invasive lesions, the tumor-adjacent normal tissue samples were integrated, and the expression of pro-inflammatory genes was evaluated in myeloid cell clusters. The differentially expressed genes specific to tumor-associated macrophages and neutrophils were used as gene signatures. These signatures were used to perform gene set variational analysis in bulk RNA sequencing data from 54 patients, and the scores were evaluated and compared between African American and non-African American samples with different metadata conditions. Significance analysis was performed on the GSVA scores between populations and the p-values were calculated. Finally, power analysis was conducted, which estimated the optimal sample size needed to achieve 80% statistical power for future studies.
Results from scRNA-seq revealed pro-tumorigenic macrophage and neutrophil populations marked by IL1B within tumor-adjacent lung parenchyma from African Americans. In addition, the GSVA analysis on bulk RNA-seq showed signal of increased macrophage and neutrophil scores in African Americans versus Whites though these were not significant due to limited sample size. Further analyses in additional samples are warranted to determine whether these populations have a significant association with the increased incidence of lung cancer in African Americans, and to also further associate with environmental factors including air pollution and social deterministic features
Beyond Pure and Impure Form. Form, Language, and Posthumanity in S. I. Witkiewicz's The Shoemakers
No full textThis dissertation studies Stanisław Ignacy Witkiewicz’s final play The Shoemakers (1934) as a key moment of internal transformation of his own discourse. An author often deemed either graphomanic or intransigent, the dissertation posits that these traits are two sides of an internal unworking [désœuvrement] and that this unworking reaches a critical moment in the play, one that reformulates internal heterodoxy, particularly as regards his aprioristic view on the end of humanity, to one with potential for anthropogenesis, in the same process deconstructing his formal-autonomous framework of Pure Form. The unworking is performed by exploiting a number of latent potentialities in the Pure Form framework: The end of humanity, an axiom in Witkacy’s historiosophy, is taken as a starting point rather than an end point, reformulating it into a horizon of posthumanity; similarly, the many revolutions of the play refocus the temporality from an imminent catastrophe to a horizon of catastrophes. Furthermore, the play has a surreptitious second tier, connecting linguistic and ontological fragments through paronomasia and aligning with profound boredom (Heidegger), making for a pure-form layer. As the linguistic and ontological disintegration of the play is motivated by its diegesis, the pure-impure form distinction underlying Witkiewicz’s Pure Form framework has been rendered an inoperable; what remains is an aesthetic of “Unimpure Form.
Impact of Student Diversity in Medical Schools on Physician Workforce in Medically Underserved Areas
No full textHealth disparities persist in the United States, with one significant contributing factor being the geographic and specialty maldistribution of physicians. This imbalance leads to a shortage of primary care physicians and limited access to healthcare in some areas. Medical schools have been identified as playing a key role in addressing these disparities by diversifying the physician workforce.
This retrospective cohort study, utilizing statistical analysis of secondary data, aimed to empirically determine the relationship between the racial/ethnic diversity of students in U.S. medical schools and two key outcomes: the proportion of graduates entering primary care practice, and the proportion of primary care physicians practicing in medically underserved areas (MUAs). Two measures of diversity were used as predictor variables: the Diversity Index Score (DIS), reflecting the probability that any two randomly selected graduates belong to different race/ethnic categories, and the proportion of graduates from racial/ ethnic groups underrepresented in medicine (PURMG).
Regarding the first outcome, we found that an increase in DIS was associated with a decreased likelihood of graduates entering primary care, across all levels of PURMG within the study sample. However, the negative effect of DIS was less pronounced at higher levels of PURMG.
With respect to the second outcome, the relationship between DIS and primary care physicians practicing in MUAs was found to vary with PURMG levels. At higher PURMG levels, an increase in DIS was associated with a steep decline in the proportion of primary care physicians in MUAs. At lower levels of PURMG, there was no effect on the relationship between DIS and the proportion of physicians practicing in MUAs.
We conclude from this study that a narrow focus on increasing racial/ethnic diversity or the proportion of URiM students in medical schools may not achieve the purpose of increasing the number of physicians in primary care practice, or those practicing in medically underserved areas. Several personal and institutional factors and the practice environment of primary care centers, especially those located in medically underserved areas, play a role in students’ career choices. Closer examination of the structure and dynamics of institutions, and the perceptions and behavior of students, faculty, and leadership is required to better understand the factors promoting such career decisions and practice locations. Meanwhile, other strategies need to be evaluated and implemented to achieve the optimal physician: population ratio in underserved areas
A Qualitative Analysis of Surgical Residents Pursuing Medical Education Training
No full textObjective: To investigate why surgical residents pursue dedicated formal training in medical education and to understand the factors contributing to their ability to accomplish this training.
Design: A qualitative analysis of semi-structured interviews using the Framework Method.
Setting: Virtual interviews conducted via Zoom within the United States.
Participants: Surgical faculty and general surgery residents who were either currently or recently enrolled in a medical education graduate program and/or surgical education fellowship while a trainee in an ACGME-accredited general surgery residency program.
Results: Participants described four main categories of factors contributing to why and how they pursued medical education training: structural, interpersonal, personal, and symbolic. Structural factors included institutional support and financial accessibility, while interpersonal influences encompassed mentorship, peer networks, and familial encouragement. Personal motivations revolved around a passion for teaching and long-term career aspirations. Symbolic influences included cultural perceptions of surgical education and its recognition as a legitimate academic discipline.
Conclusions: Surgical residents’ ability to pursue medical education training is heavily influenced by the structure of their residency program, the availability of high-quality mentorship, and financial resources. As more surgical residents demonstrate a professional interest in surgical education, residency programs should integrate formal training pathways and provide institutional support to increase accessibility. Addressing these barriers can enhance the pipeline of well-trained surgical educators who contribute to the advancement of surgical education research and medical education
Barriers and Facilitators in Providing Orthodontic Care for Children with Special Health Care Needs
No full textOrthodontic care for children with special health care needs (CHSCNs) presents unique challenges and opportunities. Despite its importance, limited research exists on factors influencing orthodontists’ ability and willingness to treat CHSCNs. This study aims to identify barriers and facilitators impacting orthodontic care for CHSCNs, examining practitioner demographics, practice characteristics, and attitudes toward this population. A survey of practicing orthodontists in Illinois collected data on key variables, including age, gender, race, ethnicity, years in practice, and practice type. Additionally, it assessed orthodontists' experience, confidence, and interest in treating CHSCNs, alongside specific barriers and facilitators encountered.
Results revealed the highest-rated facilitator to be the desire to help those with special needs, while patient compliance emerged as the most significant barrier. Relationships between orthodontists’ characteristics and their experience, confidence, and interest in treating CHSCNs were observed. Notable factors, such as age, race, ethnicity, and practice type, were significantly associated with care provision for CHSCNs.
This research offers valuable insights into factors influencing orthodontic care for CHSCNs, with potential implications for orthodontic education, practice management, and policy development in special needs dentistry. By highlighting key barriers and facilitators, the study informs strategies to enhance access and quality of care for this underserved population. Ultimately, this work supports the broader goal of improving orthodontic services and addressing disparities in dental care for CHSCNs
Examining Potential Mediators of the Association of Neighborhood SES with Prostate Cancer Survival
No full textProstate cancer is the most common non-melanoma cancer among men and the second leading cause of cancer death among men in the United States. Despite survival rates greater than 98% for local stage disease, non-Hispanic Black / non-Hispanic White differences in prostate cancer survival remain. Non-Hispanic Black men, who are more likely to reside in socioeconomically disadvantaged areas, have the highest death rate for prostate cancer of any racial or ethnic group in the US. Low SES census tract or block group is associated with lower prostate cancer-specific survival. Racial/ethnic prostate cancer death-related disparities tend to be attenuated in analyses that also account for area-level SES. This study investigated the potential mediators of the relationship between area-level socioeconomic status, as measured by a composite variable called concentrated disadvantage, and prostate cancer survival to shed light on non-Hispanic Black non-Hispanic White prostate-specific survival differences. Findings include that equalizing by hospital medical affiliation, hospital safety net designation, hospital prostate cancer treatment volume or surgery with curative intent reduces the association between census-tract concentrated disadvantage and prostate cancer survival. Differences were found between which mediators were most effective for non-Hispanic Black men compared to non-Hispanic White men such that surgery and safety net status were the mediators of greatest influence among non-Hispanic Black men and medical school affiliation and hospital prostate cancer treatment volume were the mediators or greatest influence among non-Hispanic White men
Integrative Assessment Methodologies for Sustainable Building Envelope Systems in Climate Adaptation
No full textThe built environment, particularly its envelope systems, accounts for 40% of electricity consumption and 40% of carbon dioxide emissions in the U.S. The focus of this research is to address key challenges in building technology, including decarbonization, climate resilience, circular economy, and balanced environmental stewardship by developing and integrating innovative assessment methodologies for sustainable building envelope systems. Decarbonization efforts target reductions in greenhouse gas emissions through energy efficiency, electrification, renewable energy, and reducing non-combustion emissions. This research emphasizes energy efficiency through advancements in continuous insulation (CI) systems, which improve thermal performance, reduce air and water leakage, and optimize HVAC systems in buildings. The thermal performance of CI systems along with the impact of thermal bridging in rainscreen systems across various climate conditions, are studied using experimental and computational analyses, ensuring enhanced building thermal performance and energy efficiency. Climate resilience is critical for built environment to adapt to extreme climate events like heatwaves and floods. This research examines the hygrothermal performance of CI wall systems under harsh cold conditions, addressing thermal and moisture issues. The findings provide strategies for durable wall designs, which are crucial for occupant health and cost-effective maintenance. Similarly, the circular economy principles guide the investigation into material degradation and its impact on hygrothermal performance. By analyzing the aging effects on wall systems, the study identifies strategies to prolong material lifespan, optimize maintenance, and ensure long-term energy efficiency. Balanced environmental stewardship is studied in this research, focusing on overburdened communities facing disproportionate climate risks. The study explores the window contribution air leakage in residential buildings, advocating for improving indoor air quality and energy efficiency. This comprehensive study not only advances sustainable building technologies but also proposes critical updates to simulation tools, emphasizing the inclusion of thermal, moisture, and aging factors in design considerations. By aligning with decarbonization, resilience, and environmental goals, the research paves the way for integrating innovative methodology assessments building envelope designs that address pressing hygrothermal, aging, and environmental challenges
Envisioning Queer Chicanx Futures: Testimonios of Trans, Non-Binary y Queer Chicanx Educators in Chicago
No full textEnvisioning Queer Chicanx Futures in Education: Testimonios of Trans, Non-Binary y Queer (TQNB) Chicanx Educators in Chicago is a poem, a love letter to what is possible when we are committed to meeting the basic human needs of TQNB educators and youth. This intimate portrayal of the lived experiences among the six Chicanx educator testimonios requires us to reflect on the following questions : What kinds of cariño (care) is possible for Trans, Queer, and Non-Binary youth from Trans, Queer, and Non-Binary educators in and out the systems of education? More importantly, What can we learn from the lived experiences of Trans, Queer, and Non-Binary educators of color and their positionality in Chicago, that can help leverage and (re)imagine the purpose of education, where it happens, and who qualifies as an educator?
Through Testimonio methodology, Cariño framework and Chicana Feminist Zine making, the purpose of this dissertation is to analyze how the lived experiences of Trans, Queer and Non-binary (TQNB) Chicanx educators in Chicago make futuristic, creative, and activist interventions toward queering education. Above all, this research provides a counter-future for Trans, Non-Binary, and Queer youth of color who are conditioned to think that people like us are not deserving of education/learning spaces grounded in radical care; it allows them to envision their lives as a liveable one, where they know that people will listen and are waiting to welcome their testimonios with open minds and hearts. Lastly, this dissertation creates a literal documentation of our collective voices on pages, in places that we know aren’t meant for us. The four affirming findings that arose from this work are Cariño as a pedagogical framework, healing through Chicana Feminist zine making, Resisting Professionalism through queer fashion/aesthetics, and Contesting Heteronormative Education
Provider Reported Influences in Delivering Interceptive Orthodontics
No full textMalocclusion affects 39% to 93% of children and adolescents globally, with variations influenced by geography and socioeconomic factors. The American Association of Orthodontists (AAO) recommends interceptive orthodontics to guide jaw growth and prevent malocclusion progression. This study surveyed 79 dental providers to assess confidence and clinical practices in interceptive orthodontics. Results showed 53.8% had low confidence, with general dentists reporting the least confidence compared to orthodontists and pediatric dentists (p < 0.001). Confidence correlated with specialty training, yet 75.6% of providers acknowledged its importance. Key barriers included financial constraints and inadequate predoctoral training. While 71.8% recognized its effectiveness, many general dentists struggled with managing pediatric patients. Findings highlight the need for improved education and training to enhance provider confidence and expand early orthodontic interventions, improving public health outcomes and access to care
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