Digital Commons Network^™

Advances In Magnetic Nanoparticles For Molecular Medicine, Xiaoyue Yang, Sarah E. Kubican, Zhongchao Yi, Sheng Tong

Markey Cancer Center Faculty Publications

Magnetic nanoparticles (MNPs) are highly versatile nanomaterials in nanomedicine, owing to their diverse magnetic properties, which can be tailored through variations in size, shape, composition, and exposure to inductive magnetic fields. Over four decades of research have led to the clinical approval or ongoing trials of several MNP formulations, fueling continued innovation. Beyond traditional applications in drug delivery, imaging, and cancer hyperthermia, MNPs have increasingly advanced into molecular medicine. Under external magnetic fields, MNPs can generate mechano- or thermal stimuli to modulate individual molecules or cells deep within tissue, offering precise, remote control of biological processes at cellular and molecular …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integrity of the intestinal epithelium plays a key role in inflammatory diseases and gastrointestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differentiation. Repression of endogenous miR-27a-3p leads to increased enterocyte differentiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell differentiation and proliferation at …

Association Between Education And Allostatic Load With Risk Of Cancer Mortality Among Hispanic Women, Melissa Lopez-Pentecost, Cynthia Li, Marlo Vernon, Sydney P. Howard, Jessica Amezcua, Justin Xavier Moore

Markey Cancer Center Faculty Publications

Purpose: Cancer remains the leading cause of death among Hispanics in the US. While social determinants of health, such as educational attainment, have been linked to negative health outcomes, their biological mechanisms remain poorly understood. We evaluated the association between educational attainment and allostatic load (AL), a measure of chronic physiologic stress, with risk of cancer mortality in Hispanic women from the National Health and Nutrition Examination Survey (NHANES).

Methods: We performed a retrospective analysis among 5637 Hispanic women in NHANES from 1988 to 2010 with follow-up data through 2019. Educational attainment was categorized into a two-level variable: less than …

Tracking Community Outreach And Engagement Activities Among National Cancer Institute-Designated Cancer Centers, Todd Burus, Caree R. Mcafee, Pamela C. Hull, Amy E. Leader, Christopher Mcnair

Markey Cancer Center Faculty Publications

The National Cancer Institute’s (NCI) Cancer Center Support Grant mandates that NCI-designated cancer centers establish a Community Outreach and Engagement (COE) component to help direct efforts at reducing cancer burden within their catchment areas. Despite the critical role of COE offices, little is known about how they track and evaluate outreach activities and outcomes. We gathered information on current practices from representatives of 40 out of 65 COE offices using an online survey. Although nearly all responding centers (97.5%) tracked COE activities, no consensus existed on resources used, and satisfaction with current solutions was mixed (51.0% not satisfied). Respondents expressed …

Biparental Inheritance Of Germline-Specific Chromosomes In The Sea Lamprey And Their Roles In Oocytes, Vladimir A. Timoshevskiy, Nataliya Timoshevskaya, Kaan İ. Eşkut, Kasturi Rajandran, Jeramiah J. Smith

Markey Cancer Center Faculty Publications

Many eukaryotic species undergo programmed elimination of specific chromosomes during embryogenesis, typically retaining these chromosomes only in their germ cells. In some species, programmatic elimination of GRCs, or sex chromosomes, also occurs in a sex-specific manner, with specific chromosomes being transmitted or eliminated by only one sex. As such, these chromosomes provide a unique perspective on the evolution of gene functions that are advantageous to the germline and genetic tradeoffs between somatic vs germline or oocyte vs sperm biology. While GRCs have been extensively characterized in male sea lampreys (Petromyzon marinus), the status of GRCs in females has not yet …

Cabozantinib Selectively Induces Proteasomal Degradation Of P53 Somatic Mutant Y220c And Impedes Tumor Growth, Fang Lin Lv, Lu Zhang, Cheng Ji, Lei Peng, Mingxian Zhu, Shumin Yang, Shunli Dong, Mingxuan Zhou, Fanfan Guo, Zhenyun Li, Fang Wang, Youguo Chen, Jinhua Zhou, Xingcong Ren, Genhai Shen, Jin-Ming Yang, Bin Li, Yi Zhang

Markey Cancer Center Faculty Publications

Inactivation of p53 by mutations commonly occurs in human cancer. The mutated p53 proteins may escape proteolytic degradation and exhibit high expression in tumors and acquire gain-of-function activity that promotes tumor progression and chemo-resistance. Therefore, selectively targeting of the gain-of-function p53 mutants may serve as a promising therapeutic strategy for cancer prevention and treatment. In this study, we identified cabozantinib, a multikinase inhibitor currently used in the clinical treatment of several types of cancer, as a selective inducer of proteasomal degradation of the p53-Y220C mutant. We demonstrate that cabozantinib disrupts the interaction between p53Y220C and USP7, a deubiquitylating enzyme, resulting …

Cisplatin-Loaded M1 Macrophage-Derived Vesicles Have Anti-Cancer Activity In Osteosarcoma, Namrata Anand, Joseph Robert Mccorkle, David Schweer, Lan Li, Kristen S. Hill, Melissa A. Fath, Derek B. Allison, Christopher L. Richards, Jill M. Kolesar

Markey Cancer Center Faculty Publications

Osteosarcoma (OS) is a relatively rare bone malignancy that primarily affects children and young adults and is associated with significant morbidity and mortality. Cisplatin is a mainstay of treatment, but its efficacy is limited by off-target toxicities. Immunotherapy is not effective due to a poor antigenic tumor microenvironment. Here, we address these challenges by using manufactured M1 macrophage-derived vesicles (MVs) loaded with cisplatin. Human blood and mouse RAW 264.7 M1 macrophages were used to prepare empty (E-MVs) and cisplatin-loaded MVs (C-MVs). Human OS cell lines were used in vitro and in a tibia xenograft mouse model to evaluate the anti-cancer …

Examining Associations Between Sociodemographic Characteristics And Ever Breastfed Children, Nhanes 1999–2020, Jessica Amezcua, Lindsey M. West, Camelia Malkami, Marlo M. Vernon, Elinita Pollard, Justin X. Moore

Markey Cancer Center Faculty Publications

Although breastfeeding provides health benefits to both mother and child, this study aimed to explore whether disparities in breastfeeding continue to exist, particularly among non-Hispanic Black (NHB) mothers and children. We performed a cross-sectional analysis among 19,830 children in the United States (US) using the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2020. Breastfeeding initiation and duration rates increased overall from 1999 to 2020. Children who were ever breastfed were more likely to have higher body weight, older mothers, mothers who did not smoke during pregnancy, a higher family poverty–income ratio (PIR), food security, mothers in …

Examining Geographic Disparity: Variation In Cancer Outcomes Within Appalachia, Todd Burus, Pamela C. Hull, Krystle A. Lang Kuhs, Tianyan Gao, Christine F. Brainson, B. Mark Evers

Markey Cancer Center Faculty Publications

BACKGROUND: 

The Appalachian region of the US extends from the Mississippi Delta to southern New York. Although disparities in Appalachian cancer outcomes have long been observed, recent rates and trends have not been assessed.

STUDY DESIGN: 

We calculated 5-year age-adjusted US cancer incidence and mortality rates for 2017 to 2021, stratified into Appalachian and non-Appalachian populations, as well as Appalachian subregions, using the US Cancer Statistics Incidence Analytics Database and National Center for Health Statistics mortality files. Annual rates for 2004 to 2021 were also calculated.

RESULTS: 

In 2017 to 2021, all-site cancer incidence (466.6; 95% CI 465.5 to 467.6) …

Health Care Access Domains And Treatment As Mediators Of Ovarian Cancer Racial Disparities In Survival: A Structural Equation Modeling Analysis In Seer-Medicare, Clare Meernik, Quan Chen, Lauren E. Wilson, Ashwini Joshi, Fariha Rahman, Maria Pisu, Margaret Liang, Kevin C. Ward, Margaret Gates Kuliszewski, Thomas Tucker, Andrew Berchuck, Bin Huang, Tomi Akinyemiju

Markey Cancer Center Faculty Publications

Racial differences in health care access (HCA) may contribute to disparities in ovarian cancer (OC) survival. We used structural equation models (SEMs) to examine associations between race and HCA domains (affordability, availability, accessibility) in relation to overall and OC-specific mortality. Non-Hispanic (NH)–Black and non-Black (Hispanic, NH-White) women diagnosed with OC in 2008-2015 were identified from Surveillance, Epidemiology, and End Results–Medicare. Cox proportional hazards regression was used to conduct mediation analysis for associations between race and HCA domains with overall and OC-specific mortality. SEM models adjusting for demographic and clinical covariates were used to estimate hazard ratios (HRs) and 95% CIs. …

Development Of Genome-Scale Technologies For Writing And Recoding Cyanobacteria, Laura Beth Quinto

Yale Graduate School of Arts and Sciences Dissertations

Diverse microorganisms have delivered unique solutions in medicine, food, energy, and nutrient cycling through atmospheric gas fixation. Yet despite tremendous progress in model organisms like E. coli and S. cerevisiae, tools for editing and predictably manipulating undomesticated species – which comprise the vast majority of microbes1 – remain scarce. Cyanobacteria, with their light- and CO₂-powered metabolism, hold particular promise for bioproduction, bioremediation, and in situ fertilization, but have been difficult to engineer. Furthermore, many of the most valuable applications of cyanobacteria would involve implementation in an open system. Such strains require two critical safeguards: biocontainment to ensure that their propagation …

Characterizing Somatic Variants In Nanopore Data With Machine Learning, Shwethal Sayeeram Trikannad

Master's Projects

Oxford Nanopore Technology (ONT) is a popular long-read sequencer in genomics. However, its high base-calling error rate produces several sequencing artifacts. Detection of somatic variants in ONT sequenced tumor-normal samples remains challenging due to low frequencies. In this study, machine learning was applied to a dataset created by benchmarking ClairS output against HCC1395 and colo829 truth sets to classify variants and artifacts. Relevant features were engineered from sequence context and variant site characteristics to model artifact profiles. HistGradientBoostingClassifier achieved 0.876950 accuracy, outperforming all other models. Variant quality was the top predictor with an aggregate accuracy of over 85%. This work …

Leadership And Management In Action Program (L-Map) Supplement: Case Studies For Humanities And Social Sciences, Giovanna Bonadonna Ph.D., Kevin Kadowaki Ph.D., A. Patricia Mendoza Ph.D., Matthew Thompson Ph.D., Shirl Yang Ph.D.

Office of Postdoctoral Affairs

The Leadership and Management in Action Program (L-MAP) Workbook and Facilitator Guide are authored by Erin Heckler, Ph.D., Jessica A. Hutchins, Ph.D., Molly Grisham, M.A., and Elizabeth Luckman, Ph.D., M.B.A. The L-MAP Project was supported by a Burroughs Wellcome Fund (BWF) Career Guidance for Trainees grant to Washington University in St. Louis, 2019-2021 (co-principal investigators: Erin Heckler, Ph.D., and Jessica Hutchins, Ph.D.).

This Supplement does not (nor does it intend to) replace the L-MAP curriculum. The case studies in this document are designed to accompany the theory in the L-MAP curriculum applying it to discipline-specific situations in the humanities and …

Social Support And Gratitude In Adolescents: An Exploratory Study, Mimi Webb Kurtz

Theses and Dissertations

Dispositional gratitude is a construct associated with numerous benefits in youth. However, existing research has primarily focused on the outcomes of gratitude, with limited exploration of the underlying factors that may contribute to individual differences in its development. Because gratitude is considered malleable, identifying key factors associated with its growth in youth is essential. The present study aims to address this gap by exploring perceived social support as a presumed antecedent of dispositional gratitude in older adolescents. Cross-sectional, self-report data and structural equation modeling were used to assess the relationship of perceived social support with gratitude levels among high school …

Cerebellar Contributions To Speech And Clinical Outcomes In Stroke: A Multimodal Investigation Of Structural Integrity Across Chronic And Acute Cohorts, Makayla Joy Gibson

Theses and Dissertations

This dissertation investigates the critical role of the cerebellum in speech production, with a focus on chronic post-stroke apraxia of speech (AOS), lesion-related cerebellar degeneration, and age-related changes in cerebellar structure among healthy individuals. While speech deficits have traditionally been attributed to cortical lesions, mounting evidence suggests that the cerebellum contributes significantly to speech-motor planning, execution, and error correction. Using multimodal neuroimaging, lesion-symptom mapping, and standardized speech assessments, this research examines cerebellar gray matter volume (GMV) across three complementary studies.

Aim 1 evaluates the association between cerebellar GMV and AOS severity in individuals with chronic left hemisphere stroke. Findings support …

Involvement Of Integrated Stress Response In Primary And Secondary Dystonia, Tricia Aleena Dulice Simon

Theses and Dissertations

ABSTRACT Dystonia is the third most common movement disorder in the United States of America , the first two being essential tremor and Parkinson’s disease. Gaining mechanistic knowledge about pathobiology of dystonia is essential for development of effective therapies. As the only therapies currently available are invasive procedures such as deep brain stimulation (DBS) or frequent botulinum toxin injections, it is critical to understand the underlying molecular mechanisms leading to dystonia. A maladaptive integrated stress response (ISR) involving dysregulation of the eukaryotic translation initiation factor  (eIF2) mediated signaling is observed in DYT-PRKRA patient cells. Mutations in PRKRA gene, which …

Defining Barriers In Pulmonary Hypertension: Pulmonary Hypertension In Remote And Rural Settings In Australia: An Epidemiologic Study Aided By Echocardiography, Pyi Naing

Theses

Pulmonary hypertension (PH) is a common, complex, and potentially lethal haemodynamic condition with many underlying aetiologies. It is poorly understood, and diagnosis is usually made late in the disease process resulting in poor outcomes even in the developed world. An innovative universal framework is required to achieve early and accurate diagnosis for improved outcomes, especially in remote and rural areas. The thesis documents my substantial body of work that unlocks a collective framework to assist patients with PH, particularly in areas not classically serviced by tertiary level PH care.

The first chapter of my thesis outlines the history, important milestones …

The Impacts Of Mentorship On An Asian American Female Pk-12 School Leader: An Autoethnography, Jessica Proctor

Education Dissertations

Asian American women remain significantly underrepresented in PK-12 school leadership roles in the United States, despite the rapid growth of the Asian American population. Existing research on women of color in educational leadership has primarily focused on Black and Latina women, leaving Asian American women’s experiences largely unexplored. This autoethnographic dissertation examines the experiences of an Asian American female leader in PK-12 education, with a particular focus on the role of mentorship in career progression and identity development. By analyzing personal experiences through the lens of historical and contemporary barriers, including racism, sexism, and limited access to networks, this study …

The Tyrant King Of The Auction House: The Disastrous “Fine Artification” Of The Dinosaur, Amelia C. Kolstad

Anthós

This article examines how fine art auctioneers market dinosaur fossils as art pieces to wealthy collectors, depriving the paleontological field of specimens for scientific research. Drawing from recent examples of fossils sold at fine art auctions, this article notes how rising auction prices for specimens as ‘art’ prevent museums and research institutions from acquiring specimens for research and restoration. Kolstad concludes that the art auction houses’ marketing of fossils as art is detrimental to paleontological research. To protect fossils and their scientific value, Kolstad proposes alternatives, such as selling replicas to collectors and highlighting the importance of original specimens for …

Cholesterol Modulation Of Bk Currents And Cerebral Artery Diameter Via Channel-Forming Alpha-Subunit, Elizabeth Schneider

Theses and Dissertations (ETD)

Voltage- and calcium-gated, large conductance potassium channels (BK; MaxiK) are ubiquitously expressed and subsequently mediate numerous physiological processes. Cholesterol is consumed in high amounts with the diet and accumulates in cellular membranes when plasma levels become elevated. Cholesterol is a known inhibitor of BK channels and is suspected of contribution to many pathophysiological issues via its interaction with these channels. However, the molecular mechanisms that drive cholesterol inhibition of BK channels remain largely unexplored. This dissertation hypothesized that cholesterol inhibits BK currents via binding to specific amino acid(s) of the channel-forming alpha subunit, and involving distinct modifications of channel gating. …

Sars-Cov-2 Variants Of Concern: Biological Implications Of Immunogenicity And Comorbidity, Jacob Nichols

Theses and Dissertations (ETD)

When coronavirus disease 2019 (COVID-19) emerged in human populations in late 2019, there was nothing known about the virus, SARS-CoV-2, besides that it had a high degree of similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). The prior published research on these viruses set a strong foundation for the research approaches needed to quickly stand-up medical countermeasures for treatment of COVID-19. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) soon revealed a high propensity to evolve new variants that could engage host cell receptors with greater affinity and escape host immunity. With each wave …

Integrative Approaches In Colorectal Cancer: Prognostic Biomarkers And Ai-Driven Hypothesis Generation For Early Diagnosis And Drug Resistance, Heliang Yin

Theses and Dissertations (ETD)

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with early diagnosis being critical for improving patient outcomes. This study addresses two key aspects of CRC research: understanding its etiology and prognostic biomarkers and exploring the role of artificial intelligence (AI) in generating hypotheses for early diagnosis. In the first project, we analyzed prognostic biomarkers in CRC, revealing a significant negative correlation between TP53 and CD56 mutations, which have opposing effects on patient survival. TP53, a tumor suppressor gene, is frequently mutated in CRC, while CD56, a glycoprotein involved in cell adhesion, may act as a cancer enhancer. …

Characterization Of Novel Hantaviruses In Paraguay, Ifebuche Nnamani

Theses and Dissertations (ETD)

The genus Orthohantavirus, is a group of tripartite, negative-sense RNA viruses of which some members are the etiologic agents for hemorrhagic fever with renal syndrome (HFRS) or orthohantavirus cardiopulmonary syndrome (HCPS) in the Old and New Worlds, respectively. Sampling of wild rodents for these viruses has increased our knowledge of their host range and continues to lead to the discovery of new orthohantaviruses species and strains. HFRS and HPS have case fatality rates of up to 15% and 40%, respectively. And in some years, morbidity rates of up to 100,000 cases can be reached, globally. The epidemiological evidence of human-to-human …

Examining The Distribution And Predictability Of Population Dynamics Across Geographic Space, Cleber Ten Caten

Theses and Dissertations

Populations occupy different regions of the geographic space and may experience distinct conditions over time that can cause fluctuations in their number of individuals. Environmental conditions, dispersal events, and resource availability are some of the factors that influence populations. A central goal in ecology has been to develop generalizations about how these factors that affect population dynamics are structured in geographic space. However, limited knowledge about where species occur and a lack of long-term surveys of populations has hindered the development, and validation, of such generalizations. In this dissertation, I use a combination of observational data, simulations, and experimental approaches …

Surface Morphology And Moisture Adsorption/Desorption Characteristics Of Hybrid-Dielectric Moisture Sensors, Ronak Ali

Theses and Dissertations--Electrical and Computer Engineering

Relative humidity sensors are used for high-humidity measurement. Moisture sensors, or dew point sensors are used for low-humidity measurement (< 1 ppm_v). The dissertation contains two parts of studies. In the first part, the effect of surface morphology on the response speed of moisture sensors is studied. Moisture sensors using α-Al₂O₃ films as porous dielectric materials deposited by anodic spark deposition are studied. In this part of the study, a variety of small pores have been studied to investigate the response speed of moisture sensors. Three different surface morphologies have been studied using scanning electron microscopy. One …

Long Oligos: Direct Chemical Synthesis Of Genes With Up To 1728 Nucleotides, Yipeng Yin, Reed Arneson, Yinan Yuan, Shiyue Fang

Michigan Tech Publications

The longest oligos that can be chemically synthesized are considered to be 200-mers. Here, we report direct synthesis of an 800-mer green fluorescent protein gene and a 1728-mer Φ29 DNA polymerase gene on an automated synthesizer. Key innovations that enabled this breakthrough include conducting the synthesis on a smooth surface rather than within the pores of traditional supports, and the use of the powerful catching-by-polymerization (CBP) method for isolating the full-length oligos from a complex mixture. Conducting synthesis on a smooth surface not only eliminated the steric hindrance that would otherwise prevent long oligo assembly, but also, surprisingly, drastically reduced …

The Effects Of Physical Exercise On Emotion Dysregulation In Postsecondary Students With And Without Adhd, Elizabeth Bodalski

Theses and Dissertations

Emotion dysregulation is a common issue among college students with ADHD, and emotion dysregulation in adults with ADHD is associated with many negative outcomes including higher levels of psychological distress and social impairment, poorer functioning at school and work, greater symptoms of anxiety and depression, and lower quality of life. Past work suggests that physical exercise can be useful in treating core ADHD symptoms for children and adolescents with ADHD, but less is known about its effects for young adults with ADHD. Exercise has been shown to be effective in targeting emotion dysregulation among the general adult population. Some work …

The Everyday Scientist: Down In The Weeds In The Heart Of The South, Pamela Zendt

Master's Projects

The Everyday Scientist: Down in the Weeds in the Heart of the South is a creative nonfiction capstone project that was released as a book. The narrative documents my two-year journey as a community scientist and explores how ordinary people contribute meaningfully to scientific research in the natural world. Rooted in my desire to connect my passion for the outdoors with the goals of the Master of Arts in Professional Writing program, this project illustrates that environmental science is not only for trained professionals. Instead, it thrives on the curiosity, dedication, and participation of volunteers who follow established protocols, collect …

Grounded Practice: Leadership And Integrity In Complex Systems, Tonja Smith

Graduate Student Portfolios, Professional Papers, and Capstone Projects

This portfolio presents the integration of advanced social work competencies developed through the Master of Social Work program at the University of Montana. Grounded in evidence-informed practice, the work demonstrates applied skills in assessment, intervention, group facilitation, policy practice, and interagency collaboration across rural and multidisciplinary settings. Artifacts highlight structured approaches to Batterer Intervention Groups, Domestic Violence Inventories, Family Group Conferencing, and Supported Education, with an emphasis on accountability, safety, and culturally responsive engagement.

The narrative analyzes how positionality, reflective practice, and cultural humility shape professional judgment, particularly when navigating structural inequities and conflicting system demands. The portfolio illustrates the …

Msw Portfolio, Amy Sanders

Graduate Student Portfolios, Professional Papers, and Capstone Projects

MSW Portfolio through the lens of "otherness".