Medicine and Health Sciences Commons^™

Fork It, Kylee Pipgrass

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Obesity prevalence is at an alarmingly high rate within the United States, but especially in rural areas of Kentucky. Obesity can lead to a variety of negative physical health outcomes including heart disease, diabetes, stroke, and some cancers. There are also mental disorders associated with obesity through mechanisms such as weight stigma and self-perception. Similar to obesity rates, prevalence and mortality associated of these health outcomes are also seen at disproportionately higher rates in rural, Appalachian Kentucky. Causes for increased obesity and obesity related consequences include some genetic factors as well as behavioral factors like physical inactivity, poor diet, stress, …

Epidemiology Of Angiosarcomas In Kentucky, 2000-2019, Emma Gough

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background/Objective: Angiosarcomas are rare, highly aggressive malignant soft-tissue sarcomas of vascular or lymphatic origin. The purpose of this study is to describe geographical distribution of angiosarcoma in Kentucky and to examine the epidemiology of angiosarcoma in Kentucky from 2000 to 2019, including the most common sites where angiosarcomas occurred and risk factors affecting survival. Methods: A sample of 246 angiosarcoma patients was received from the Kentucky Cancer Registry (KCR). Kaplan-Meier curves were produced to examine overall survival, as well as survival by age, insurance type, tumor size, and SEER site. A Cox proportional hazards regression analysis was conducted to estimate …

Roadway Density And Lung Cancer Histology In Kentucky, Mahala Pettus

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The purpose of this article was to examine the relationship between a proxy measure of exposure to automotive exhaust – roadway density – and risk for adenocarcinoma lung cancer. Using data from the Kentucky Cancer Registry and the Kentucky Geoportal Data Clearinghouse, we conducted a cross-sectional study of the distribution of adult lung cancer cases by histological type across the state of Kentucky. The north-central region of Kentucky has a higher prevalence of adenocarcinomas and greater roadway density. Among adenocarcinoma cases in Kentucky, there are more non-smokers than other types of tobacco use. As smoking rates decrease in Kentucky, and …

Breastfeeding Promotion In The Workplace, Katie C. Nettesheim

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Breastfeeding is one of the best things a mother can do for her baby. It has many protective qualities including a reduced risk of sudden infant death syndrome (SIDS), asthma, obesity, type 1 diabetes, respiratory infections, ear infections, and stomach bugs for the baby (CDC, 2022). There are also protective qualities for the mother as well, including a reduced risk of high blood pressure, breast and ovarian cancer, and type II diabetes. Breastfeeding exclusively, the infant only receives breastmilk and no other supplementation for 6 months, which maximizes the many benefits that breastfeeding has.

Rural areas of the United States …

Concussion Perceptions And Reporting Behaviors By Individual And Team Sport Participation Among Female Diii Student-Athletes, Bethany L. Stewart

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Abstract

Purpose. This study aimed to analyze differences between individual and team sport participation and academic year on perception of concussion and reporting behaviors.

Methods. A cross-sectional study was conducted using original data from the Perceptions and Likeliness to Report Concussions in Collegiate Athletes survey distributed to student-athletes from April 2021 to December 2022. The study population was restricted to current residents of the United States, current enrollment in college or university, female-identifying, and between the ages of 18 and 24, yielding a final population of 135 for analysis. Statistical frequency analyses were obtained, then stratified by team and individual …

Psychosocial Outcomes Post-Concussion Of Female Collegiate Athletes, Victoria Farley

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Concussions are traumatic brain injuries impacting upwards of 3 million athletes per year. Female collegiate athletes are an essential group of athletes to investigate as they account for 47% of all collegiate athletes and often suffer more severe concussions with worse concussion symptoms than their male counterparts. Many symptoms are associated with concussion such as dizziness nausea, headaches, and instability, however, some injury symptoms extend beyond physical symptoms. The symptoms that extend beyond physical often mimic different psychosocial factors like depression and anxiety. This study investigated the associations of injury, the duration of symptoms, and the psychosocial impacts of injury …

Community Pharmacy Provision Of Extended-Release Injectable Naltrexone In Kentucky: Perspective Of People Who Use Opioids, Anye Wamucho

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Aim: To identify demographic, socio-economic, and other factors associated with likelihood of obtaining extended-release injectable naltrexone (EIN) if provided in a private space at a local pharmacy among people who use opioids (PWUO) in rural Appalachian Kentucky.

Methods: People who used opioids in the past 6 months in rural Appalachian Kentucky (n=170) completed interviewer-administered questionnaires eliciting demographic, socio-economic, and other characteristics. Participants were also asked about whether they will be more likely to obtain EIN if provided in a private space at a local pharmacy. Factors associated with increased likelihood to obtain pharmacy-provided EIN were assessed using unadjusted univariate and …

Covid-19 Vaccine Acceptance, Hesitancy, And Refusal Among Educators In Spring Of 2021, Jenifer O'Brien

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The COVID-19 pandemic provided unprecedented vaccine development and deployment. Educators were among the first non-healthcare occupations to become eligible for the vaccine, and were an early predictor of vaccine hesitancy especially among educated females. By the spring of 2021, 87% of teachers had received at least one dose of the COVID-19 vaccine. Among those who expressed hesitancy, no defining demographic factors were found. Those who expressed hesitancy commonly cited a rushed vaccine development process and fear of long term side effects as reasons against vaccination.

The Meals On Wheels-Breathitt: A Health Campaign For Reducing Food Insecurity Among The Older Adults In Breathitt County, Kentucky., Sarah Haroon

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The population of the United States of America is aging at a faster rate than ever before. More than 1 in 6 Americans are now 65 or older (The Washington Post, 2023). Since 2010, compared to people under 65, there has been close to a two-hundred percent increase in people 65 and above (The Washington Post, 2023). The rise in the aging U.S. population is due to increased life span and people living longer (U.S. Census Bureau, 2020). Furthermore, life expectancy for the total U.S. population is projected to increase by six years, from 79.7 in 2017 to 85.6 by …

Association Of Diabetes Prevalence With Labor Force Participation Rates In Kentucky Counties, Ryan Montgomery

MPA/MPP/MPFM Capstone Projects

Compared to other states in the USA, Kentucky has one of the highest rates of diagnosed diabetes and one of the lowest levels of labor force participation. This project employs a multivariable linear regression model to estimate the correlation between county-level diabetes prevalence and county-level labor force participation rates in Kentucky counties from 2015-2019, using publicly available data from the Centers for Disease Control’s Behavioral Risk Factor Surveillance System (BRFSS) and the U.S. Census Bureau’s American Community Survey (ACS). Labor force participation rates serve as the dependent variable and diabetes prevalence rates serve as the primary independent variable, alongside nine …

Uk College Of Medicine African-American Medical Students' Experience With Faculty Mentoring, Ashlee-Nicole C. Hamilton

Theses and Dissertations--Educational Policy Studies and Evaluation

This research study explored the faculty mentoring experiences of African-American medical students at the University of Kentucky College of Medicine (UK COM). The purpose of the research is to determine benefits and challenges expressed by the African-American students so that UK COM can use the student voices to improve faculty mentoring for this student population. The following broad questions guided the research: 1) What are UK College of Medicine African-American medical students’ experiences with faculty mentoring? 2) What are UK College of Medicine African-American medical students’ experience with faculty mentoring on a satellite regional campus? Specifically, the investigation seeks to …

Characterization Of The Function And Regulation Of The Hmpv Phosphoprotein, Rachel Thompson

Theses and Dissertations--Molecular and Cellular Biochemistry

Human metapneumovirus (HMPV) is a non-segmented, negative strand RNA virus (NNSV) that frequently causes respiratory tract infections in infants, the elderly, and the immunocompromised. Despite the initial identification of HMPV in 2001, there are currently no FDA approved antivirals or vaccines available. Therefore, understanding the mechanism of HMPV replication is critical for the identification of novel therapeutic targets. A key feature in the replication cycle of HMPV and other NNSVs is the formation of membrane-less, liquid-like replication and transcription centers in the cytosol termed inclusion bodies (IBs). Recent work on NNSV IBs suggests they display characteristics of biomolecular condensates formed …

Advancements In Glycogen Detection And Spatial Profiling Reveals A New Therapeutic Path For Ewing Sarcoma: A Non-Traditional Glycogen Storage Disease, Lyndsay E. A. Young

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the primary glucose storage carbohydrate in mammals, and it is synthesized in most tissues. As glycogen architecture modulates its role in metabolism, it is essential to accurately evaluate and quantify glycogen, glycogen phosphate, and chain length of glucose monomers. Simultaneous quantitation of glycogen architecture is challenging. This work describes a highly-sensitive method for the detection of both glycogen-derived glucose and glucose-phosphate esters utilizing gas-chromatography coupled mass spectrometry (GCMS). We then integrated this glycogen quantitation workflow into a routinely utilized metabolomics-based assay. The work presented describes a workflow for the normalization of polar metabolites utilizing amino acids derived from …

The Development And Characterization Of Nanobodies Specific To Protein Tyrosine Phosphatase 4a3 (Ptp4a3/Prl-3) To Dissect And Target Its Role In Cancer., Caroline Smith

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3) is an oncogenic dual-specificity phosphatase that drives tumor metastasis, promotes cancer cell survival, and is correlated with poor patient prognosis in a variety of solid tumors and leukemias. The mechanisms that drive PRL-3’s oncogenic functions are not well understood, in part due to a lack of research tools available to study this protein. The development of such tools has proven difficult, as the PRL family is ~80% homologous and the PRL catalytic binding pocket is shallow and hydrophobic. Currently available small molecules do not exhibit binding specificity for PRL-3 over PRL family members, …

Examining The Effects Of Hyperglycemia On Retinal Regeneration, Emmanuella Ec Kyllians

Theses and Dissertations--Biology

Diabetes is a disease that affects how the body processes glucose, leading to a cascade of other complications, one of which is diabetic retinopathy (DR). DR is a neurovascular disease that affects the retina and research has revealed the role of retinal neurodegeneration in its development. Animal models like zebrafish have emerged as important tools for studying the molecular and cellular mechanisms underlying DR. On the other hand, retinitis pigmentosa (RP) is a degenerative disease that involves the progressive degeneration of rods and cones, and hyperglycemia has been found to impair regeneration. Therefore, this study aims to examine the effects …

Brain Glycogen – Beyond Energy Storage In Glycogen Storage Diseases, Kia H. Markussen

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is a carbohydrate molecule that is traditionally viewed as a convenient and easily accessible energy storage form of glucose. However,emerging evidence supports the role of glycogen as more than a glucose storage form. During the last 20 years, glycogen has been shown to play pivotal roles in learning and memory, signaling events, viscosity, protein glycosylation, and be acritical hallmark in devastating diseases. Not only, does glycogen play a role as an energy substrate and critical metabolite during energy deprivation, glycogen is central for neurotransmitter homeostasis, tumor initiation, and ontributes to proper protein glycosylation in the brain. In this work, …

Protein S In Coagulation And Inflammation, Martha Mega Silvia Sim

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein S (PS) is a key regulator, which links inflammation and coagulation and performs multiple proposed functions in both processes. PS exists in the blood as a free soluble form (~40%), bound to complement component 4b-binding protein/ C4BP (~60%), and packaged in platelet α-granules (~2.5%). Subendothelial tissue factor (TF), upon exposure to blood, initiates coagulation, a proteolytic cascade which results in the activation of thrombin, the enzyme responsible for formation of a fibrin clot. PS is a critical anticoagulant that inhibits multiple steps of this process. Only the free fraction of PS has full anticoagulant properties, as C4BP blocks this …

Metabolic Reprogramming Driven By Ezh2 Inhibition Depends On Cell–Matrix Interactions, Teresa W-M Fan, Jahid M. M. Islam, Richard M. Higashi, Penghui Lin, Christine F. Brainson, Andrew N. Lane

Markey Cancer Center Faculty Publications

EZH2 (Enhancer of Zeste Homolog 2), a subunit of Poly- comb Repressive Complex 2 (PRC2), catalyzes the trimethyla- tion of histone H3 at lysine 27 (H3K27me3), which represses expression of genes. It also has PRC2-independent functions, including transcriptional coactivation of oncogenes, and is frequently overexpressed in lung cancers. Clinically, EZH2 in- hibition can be achieved with the FDA-approved drug EPZ- 6438 (tazemetostat). To realize the full potential of EZH2 blockade, it is critical to understand how cell-cell/cell-matrix interactions present in 3D tissue and cell culture systems in- fluences this blockade in terms of growth-related metabolic functions. Here, we show that …

A Monoadduct Generating Ru(Ii) Complex Induces Ribosome Biogenesis Stress And Is A Molecular Mimic Of Phenanthriplatin, Richard Joseph Mitchell, Sarah M. Kriger, Alexander D. Fenton, Dmytro Havrylyuk, Ankit Pandeya, Yang Sun, Tami Smith, Jason E. Derouchey, David K. Heidary, Edith C. Glazer

Markey Cancer Center Faculty Publications

Ruthenium complexes are often investigated as potential replacements for platinum-based chemotherapeutics in hopes of identifying systems with improved tolerability in vivo and reduced susceptibility to cellular resistance mechanisms. Inspired by phenanthriplatin, a non-traditional platinum agent that contains only one labile ligand, monofunctional ruthenium polypyridyl agents have been developed, but until now, few demonstrated promising anticancer activity. Here we introduce a potent new scaffold, based on [Ru(tpy)(dip)Cl]Cl (tpy = 2,20:60,200-terpyridine and dip = 4,7-diphenyl-1,10-phenanthroline) in pursuit of effective Ru(II )-based monofunctional agents. Notably, the extension of the terpyridine at the 40 position with an aromatic ring resulted in a molecule that …

Assessment Of Opioid-Induced Immunomodulation In Experimental And Clinical Sepsis, Brittany Dawn Bissell, Jamie L. Sturgill, Maria E. C. Bruno, Erick D. Lewis, Marlene E. Starr

Markey Cancer Center Faculty Publications

CONTEXT: Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection.

HYPOTHESIS: We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model.

METHODS AND MODELS: This was a two-phase preclinical …

Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, …

Computational Investigation Of A Series Of Small Molecules As Potential Compounds For Lysyl Hydroxylase-2 (Lh2) Inhibition, Yazdan Maghsoud, Erik Antonio Vázquez-Montelongo, Xudong Yang, Chengwen Liu, Zhifeng Jing, Juhoon Lee, Matthew Harger, Ally K. Smith, Miguel Espinoza, Hou-Fu Guo, Jonathan M. Kurie, Kevin N. Dalby, Pengyu Ren, G. Andrés Cisneros

Markey Cancer Center Faculty Publications

The catalytic function of lysyl hydroxylase-2 (LH2), a member of the Fe(II)/αKG-dependent oxygenase superfamily, is to catalyze the hydroxylation of lysine to hydroxylysine in collagen, resulting in stable hydroxylysine aldehyde-derived collagen cross- links (HLCCs). Reports show that high amounts of LH2 lead to the accumulation of HLCCs, causing fibrosis and specific types of cancer metastasis. Some members of the Fe(II)/αKG-dependent family have also been reported to have intramolecular O2 tunnels, which aid in transporting one of the required cosubstrates into the active site. While LH2 can be a promising target to combat these diseases, efficacious inhibitors are still lacking. We …

Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self- renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 …

Extracellular Vesicle Distribution And Localization In Skeletal Muscle At Rest And Following Disuse Atrophy, Ahmed Ismaeel, Douglas W. Van Pelt, Zachary Hettinger, Xu Fu, Christopher I. Richards, Timothy A. Butterfield, Jonathan J. Petrocelli, Ivan J. Vechetti Jr., Amy L. Confides, Micah J. Drummond, Esther E. Dupont-Versteegden

Markey Cancer Center Faculty Publications

Background Skeletal muscle (SkM) is a large, secretory organ that produces and releases myokines that can have autocrine, paracrine, and endocrine effects. Whether extracellular vesicles (EVs) also play a role in the SkM adaptive response and ability to communicate with other tissues is not well understood. The purpose of this study was to investigate EV biogenesis factors, marker expression, and localization across cell types in the skeletal muscle. We also aimed to investigate whether EV concentrations are altered by disuse atrophy.

Methods To identify the potential markers of SkM‑derived EVs, EVs were isolated from rat serum using density gradient ultracentrifugation, …

Glycolytic Regulation Of Intestinal Stem Cell Self-Renewal And Differentiation, Chang Li, Yuning Zhou, Ruozheng Wei, Dana L. Napier, Tomoko Sengoku, Michael Alstott, Jinpeng Liu, Chi Wang, Yekaterina Y. Zaytseva, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

BACKGROUND AND AIMS: The intestinal mucosa undergoes a continual process of proliferation, differentiation, and apoptosis. An imbalance in this highly regimented process within the intestinal crypts is associated with several intestinal pathologies. Although metabolic changes are known to play a pivotal role in cell proliferation and differentiation, how glycolysis contributes to intestinal epithelial homeostasis remains to be defined.

METHODS: Small intestines were harvested from mice with specific hexokinase 2 (HK2) deletion in the intestinal epithelium or LGR5þ stem cells. Glycolysis was measured using the Seahorse XFe96 analyzer. Expression of phospho-p38 mitogen- activated protein kinase, the transcription factor atonal homolog 1, …

Impact Of The Affordable Care Act On Providing Equitable Healthcare Access For Ibd In The Kentucky Appalachian Region, Jennifer T. Castle, Brittany Levy, Anthony A. Mangino, Hannah G. Mcdonald, Erin E. Mcatee, Jitesh A. Patel, B. Mark Evers, Avinash S. Bhakta

Markey Cancer Center Faculty Publications

BACKGROUND: Medicaid expansion improved insurance coverage for patients with chronic conditions and low income. The effect of Medicaid expansion on patients with IBD from high-poverty communities is unknown.

OBJECTIVE: This study aimed to evaluate the impact of Medicaid expansion in Kentucky on care for patients with IBD from the Eastern Kentucky Appalachian community, a historically impoverished area.

DESIGN: This study was a retrospective, descriptive, and ecological study.

SETTINGS: This study was conducted in Kentucky using the Hospital Inpatient Discharge and Outpatient Services Database.

PATIENTS: All encounters for IBD care for 2009–2020 for patients from the Eastern Kentucky Appalachian region were …

Long-Term Kidney Function Recovery And Mortality After Covid-19-Associated Acute Kidney Injury: An International Multi-Centre Observational Cohort Study, Byom W. L. Tan, Bryce W. Q. Tan, Kee Yuan Ngiam, The Consortium For Clinical Characterization Of Covid-19 By Ehr (4ce)

Markey Cancer Center Faculty Publications

Background While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking.

Methods A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021.

Findings Advanced age (HR 2.77, 95%CI 2.53–3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI.

Interpretation COVID-19-associated …

Polycomb Deficiency Drives A Foxp2-High Aggressive State Targetable By Epigenetic Inhibitors, Fan Chen, Aria Byrd, Jinpeng Liu, Robert M. Flight, Tanner Ducote, Kassandra J. Naughton, Xiulong Song, Abigail R Edgin, Alexsandr Lukyanchuk, Danielle T. Dixon, Christian M. Gosser, Dave-Preston Esoe, Rani Jayswal, Stuart H. Orkin, Hunter N. B. Moseley, Chi Wang, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 …

Suppressing Hepatic Ugt1a1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways And Lipid Species And Improves Fatty Liver Disease, Evelyn A. Bates, Zachary A. Kipp, Genesee J. Martinez, Olufunto O. Badmus, Mangala M. Soundarapandian, Donald Foster, Mei Xu, Justin F. Creeden, Jennifer R. Greer, Andrew J. Morris, David E. Stec, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and …

Impact Of The Appalachian Career Training In Oncology (Action) Program On Undergraduate Participants, Carol Hanley, Lauren Hudson, Chris Prichard, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Kentucky ranks first in the nation in cancer incidence and mortality. The Appalachian region of the state experiences the highest cancer disparities due to inequities in many social determinants of health. As a strategy for addressing cancer and education disparities in the region, the Appalachian Career Training in Oncology (ACTION) Program at the University of Kentucky Markey Cancer Center engaged 16 Appalachian-native undergraduate student participants annually in cancer-related activities. Students were recruited on an annual basis for the 2-year ACTION program. Entry, mid-point, and exit surveys were administered to participants. Classical test theory and exploratory factor analysis were used to …