Diseases Commons^™

Development Of Feature Extraction Models To Improve Image Analysis Applications In Cancer, Yu Shi

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Cancer poses a significant global health challenge. With an estimated 20 million new cases diagnosed worldwide in 2022 and 9.7 million fatalities attributable to the disease, the economic burden of cancer is immense. It impacts healthcare systems and imposes substantial costs for its care on patients and their families. Despite advancements in early detection, prevention, and treatment that have reduced overall cancer mortality rates, the growing prevalence of cancer, particularly among younger individuals, remains a pressing issue.

Recent advancements in medical imaging technology have progressed significantly with the help of emerging computer vision and artificial intelligence (AI) technology. Despite these …

Enriching The Pcos Lifestyle, Callie Coleman

Electronic Theses and Dissertations

Polycystic Ovary Syndrome (PCOS) is an endocrine disorder affecting approximately 4 – 20% of women worldwide. It is associated with insulin resistance, fertility problems, and an increased susceptibility to chronic conditions through multiple inflammatory pathways. Women with PCOS are also at increased risk for disordered eating. The Mediterranean diet is associated with decreased inflammation and risk of chronic conditions, and intuitive eating principles are associated with decreased disordered eating patterns. The purpose of this study was to determine if a six-week nutrition education workshop incorporating information and skills related to both the Mediterranean lifestyle and intuitive eating principles can improve …

Utilising Discriminant Function Analysis (Dfa) For Classifying Osteoarthritis (Oa) Patients And Volunteers Based On Biomarker Concentration, Laura Jane Coleman, John L Byrne, Stuart Edwards, Rosemary O'Hara

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a degenerative joint disease characterised by the breakdown of cartilage, causing pain, stiffness, and limited movement. Early diagnosis is crucial for effective management but remains challenging due to non-specific early symptoms. This study explores the application of Discriminant Function Analysis (DFA) to classify OA patients and healthy volunteers based on biomarker concentrations of Interleukin-6 (IL-6), Tumour necrosis factor-alpha (TNF-α), and Myeloperoxidase (MPO). DFA was employed to analyse biomarker data from 86 participants (58 patients, 28 volunteers) to evaluate the discriminatory power of these biomarkers in predicting OA. Significant differences were observed in MPO and TNF-α levels between …

Autophagic Signaling Promotes Systems-Wide Remodeling In Skeletal Muscle Upon Oncometabolic Stress By D2-Hg, Yaqi Gao, Kyoungmin Kim, Heidi Vitrac, Rebecca L Salazar, Benjamin D Gould, Daniel Soedkamp, Weston Spivia, Koen Raedschelders, An Q Dinh, Anna G Guzman, Lin Tan, Stavros Azinas, David J R Taylor, Walter Schiffer, Daniel Mcnavish, Helen B Burks, Roberta A Gottlieb, Philip L Lorenzi, Blake M Hanson, Jennifer E Van Eyk, Heinrich Taegtmeyer, Anja Karlstaedt

Faculty, Staff and Student Publications

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss.

METHODS: We quantified genomic, metabolomic, and proteomic changes in …

Pilz Domain-Containing Proteins Regulate Motility In Acinetobacter Baumannii, Gabriel Smith

Electronic Theses and Dissertations

Acinetobacter baumannii is an increasingly multidrug-resistant pathogen contributing to hospital-acquired infections, necessitating a greater understanding of how it interacts with its surroundings. Many bacteria utilize different methods of bacterial motility to move about and interact with these surroundings. A bacterial second messenger, cyclic diguanosine monophosphate (c-di-GMP), can regulate various motility factors that are potentially advantageous for survival in and adaptation to their environment. Concentrations of c-di-GMP are regulated by specific synthesizing and degrading enzymes. Controlled levels of c-di-GMP allow interaction between the c-di-GMP and its binding effectors that induce changes in bacterial phenotypes such as biofilm formation and motility. A …

Increased Risk Of Cutaneous T-Cell Lymphoma Development After Dupilumab Use For Atopic Dermatitis, Jenna Mandel, Jaanvi Mehta, Ramsay Hafer, Mahaa Ayub, Faria Nusrat, Henry Yang, Pierluigi Porcu, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

There have been several reports of dupilumab use and the development of CTCL; however, the risk of CTCL development has not been adequately evaluated at the population level. The objective of this study is to determine whether dupilumab administration for AD is associated with an increased risk of developing CTCL and to identify at-risk populations within this group. This retrospective cohort study used TriNetX, a deidentified medical record database including over 107 million patients, to identify eligible patients. Treatment and control groups were evaluated for the development of CTCL. Patients of any age with a documented diagnosis of AD were …

High Prevalence Of Artifacts In Optical Coherence Tomography With Adequate Signal Strength, Wei-Chun Lin, Aaron Coyner, Charles Amankwa, Abigail Lucero, Gadi Wollstein, Joel Schuman, Hiroshi Ishikawa

Wills Eye Hospital Papers

PURPOSE: This study aims to investigate the prevalence of artifacts in optical coherence tomography (OCT) images with acceptable signal strength and evaluate the performance of supervised deep learning models in improving OCT image quality assessment.

METHODS: We conducted a retrospective study on 4555 OCT images from 546 patients, with each image having an acceptable signal strength (≥6). A comprehensive analysis of prevalent OCT artifacts was performed, and five pretrained convolutional neural network models were trained and tested to infer images based on quality.

RESULTS: Our results showed a high prevalence of artifacts in OCT images with acceptable signal strength. Approximately …

Editorial Comment: Diversity And Disparities In Orthopaedic Surgery: Update 2024, Kimberly J Templeton, Melvyn A Harrington

Faculty, Staff and Students Publications

No abstract provided.

Factors Associated With Failed Closed Reduction In Flexion And Gartland Type Iii Pediatric Supracondylar Humerus Fractures, Pablo Coello, Nathaniel Grey Loyd, David A Hsiou, Rachel S Silverstein, Scott B Rosenfeld

Faculty, Staff and Students Publications

Background: Most displaced supracondylar humerus fractures (SCHFs) are treated with closed reduction and percutaneous pinning. While there are only a few possible indications for converting to an open reduction, a failed closed reduction is a common cause. This study aims to elucidate possible risk factors for failed closed reductions of SCHF.

Methods: A retrospective review of SCHF from 2010 to 2020 at a pediatric tertiary medical center, which underwent operative fixation, was conducted. Exclusion criteria were open fractures and reasons for open reduction other than failed closed reduction. Rates of open reduction were assessed by preoperative fracture classification and assessed …

Risk Factors For Loss To Follow Up In Pediatric Supracondylar Humerus Fractures, Nathaniel Grey Loyd, David Hsiou, Armando Martinez, Pablo Coello, Lon Kai Pang, Muhammad Hamza Shamim, Jessica Mcgraw-Heinrich, Scott B Rosenfeld

Faculty, Staff and Students Publications

Background: This study seeks to analyze risk factors associated with loss to follow up (LTF) after pin pull in pediatric patients with operatively treated supracondylar humerus fractures (SCHF).

Methods: A retrospective cohort study of patients under 18 years with operative SCHF from 2010 to 2020 was conducted. Factors of interest included LTF, age, race, language, distance to the hospital, Gartland fracture type, and Social Deprivation Index (SDI) by ZIP code. Univariate logistic regression was performed for each independent variable and significant variables were additionally analyzed with multivariate logistic regression analysis.

Results: Six hundred ninety-eight patients were included in the study. …

Image-Guided Aspiration Of A Cystic Mediastinal Teratoma: A Case Report And Literature Review, Craig R Kym, Anoop P Ayyappan, Babith J Mankidy, Mohammad Ghasemi-Rad

Faculty, Staff and Students Publications

A 51-year-old male presented to our tertiary referral hospital with progressive shortness of breath and orthopnea. A computed tomography (CT) of the chest was performed that showed a large cystic middle mediastinal mass. Magnetic resonance imaging (MRI) of the chest demonstrated a large, well-circumscribed, T2-hyperintense cystic middle mediastinal mass resulting in significant compression of the trachea, brachiocephalic artery, superior vena cava, and azygos vein. The patient subsequently developed a right hemispheric stroke due to compression of the brachiocephalic artery and was too clinically unstable to undergo or definitive operative management of the mediastinal cyst. Percutaneous CT-guided aspiration of the cystic …

Predicting Wait Time For Pediatric Kidney Transplant: A Novel Index, Alexandra Alvarez, Ashley Montgomery, Nhu Thao Nguyen Galván, Eileen D Brewer, Abbas Rana

Faculty, Staff and Students Publications

BACKGROUND: Over one thousand pediatric kidney transplant candidates are added to the waitlist annually, yet the prospective time spent waiting is unknown for many. Our study fills this gap by identifying variables that impact waitlist time and by creating an index to predict the likelihood of a pediatric candidate receiving a transplant within 1 year of listing. This index could be used to guide patient management by giving clinicians a potential timeline for each candidate's listing based on a unique combination of risk factors.

METHODS: A retrospective analysis of 3757 pediatric kidney transplant candidates from the 2014 to 2020 OPTN/UNOS …

Impact Of Frailty On Outcomes And Readmissions After Transcatheter And Surgical Aortic Valve Replacement In A National Cohort, Travis J Miles, Christopher T Ryan, Katie J Hogan, Bhavesh S Sayal, Christopher B Sylvester, Todd K Rosengart, Joseph S Coselli, Marc R Moon, Ravi K Ghanta, Subhasis Chatterjee

Faculty, Staff and Students Publications

OBJECTIVE: We examined the effect of frailty on in-hospital mortality, readmission rates, and hospitalization costs after transcatheter and surgical aortic valve replacement in a population-level cohort.

METHODS: The Nationwide Readmissions Database was queried for patients who underwent transcatheter or surgical aortic valve replacement during 2016-2018. Multivariate logistic regression was used to discern independent effects of frailty on outcomes. Kaplan-Meier time-to-event analysis was used to evaluate the effect of frailty on freedom from readmission.

RESULTS: A total of 243,619 patients underwent aortic valve replacement: 142,786 (58.6%) transcatheter aortic valve replacements and 100,833 (41.4%) surgical aortic valve replacements. Frail patients constituted 16,388 …

Hypoxaemia And Risk Of Death Among Children: Rethinking Oxygen Saturation, Risk-Stratification, And The Role Of Pulse Oximetry In Primary Care, Hamish R Graham, Carina King, Trevor Duke, Salahuddin Ahmed, Abdullah H Baqui, Tim Colbourn, Adegoke G Falade, Helena Hildenwall, Shubhada Hooli, Yewande Kamuntu, Rami Subhi, Eric D Mccollum

Faculty, Staff and Students Publications

Pulse oximeters are essential for assessing blood oxygen levels in emergency departments, operating theatres, and hospital wards. However, although the role of pulse oximeters in detecting hypoxaemia and guiding oxygen therapy is widely recognised, their role in primary care settings is less clear. In this Viewpoint, we argue that pulse oximeters have a crucial role in risk-stratification in both hospital and primary care or outpatient settings. Our reanalysis of hospital and primary care data from diverse low-income and middle-income settings shows elevated risk of death for children with moderate hypoxaemia (ie, peripheral oxygen saturations [SpO2] 90–93%) and severe hypoxaemia (ie, …

Crohn's Disease-Associated Granulomatous Pancreatitis With Exocrine Pancreatic Insufficiency, Anthony A Xu, Sara Vincent, Samuel Ma, Vanessa Catania, Neda Zarrin-Khameh

Faculty, Staff and Students Publications

Extraintestinal manifestations of inflammatory bowel disease occur commonly and can lead to considerable morbidity. Pancreatic manifestations of inflammatory bowel disease have been reported to be more common in Crohn's disease (CD) than ulcerative colitis. We report a case of granulomatous inflammation in the body of the pancreas with exocrine pancreatic insufficiency, which prompted a diagnosis switch from ulcerative colitis to CD. This is of interest to readers to remind them that pancreatic manifestations can occur and are more common in CD.

Transcecal Endoscopic Appendectomy For Management Of Complex Appendiceal Polyps Extending Into The Appendiceal Orifice, Tara Keihanian, Mai A Khalaf, Fuad Zain Aloor, Dina Hani Zamil, Salmaan Jawaid, Mohamed O Othman

Faculty, Staff and Students Publications

Background and study aims Endoscopic resection of appendiceal orifice (AO) polyps extending inside the appendiceal lumen is challenging given the inability to determine polyp lateral margins and risk of appendicitis. Transcecal endoscopic appendectomy (TEA) ensures en bloc resection of these complex polyps.

Patients and methods This case series includes patients who underwent TEA by a single endoscopist in the United States. Technical success was defined as achieving complete removal of the appendix along with AO polyp in an en bloc fashion.

Results In total, nine patients were included (mean age 69.7 ± 9.6 years). The average appendix size was 4.07 …

Using Geospatial Analysis To Identify Priority Communities For Cervical Cancer Prevention In Texas, Itunu O Sokale, Aaron P Thrift, Jane R Montealegre, Onyema G Chido-Amajuoyi, Victor T Adekanmbi, Abiodun O Oluyomi

Faculty, Staff and Students Publications

INTRODUCTION: Despite being almost entirely preventable, cervical cancer is the fourth most frequently diagnosed cancer among women worldwide. Cervical cancer incidence suggests missed opportunities for prevention. Geospatial analysis could strategically guide public health interventions. This study aimed to identify geographic clusters of cervical cancer incidence in Texas, a state with higher than national rates of cervical cancer incidence and mortality.

METHODS: In this population-based cross-sectional study, the authors analyzed incident cervical cancer data among Texas women aged 30-64 years, from 2014 to 2018. The authors conducted a purely spatial Poisson-based analysis function in SaTScan to examine geographic clusters of higher-than-expected …

Modern Perspectives On Hypertrophic Cardiomyopathy-No One Size Fits All, Brett Doliner, Hadeel Gaddar, Ramsey Kalil, Alexander Postalian

The Texas Heart Institute Journal

Despite substantial advances in the management of hypertrophic cardiomyopathy, advanced heart failure remains a major cause of morbidity in this patient population. This narrative review presents the case of a patient with hypertrophic obstructive cardiomyopathy who underwent alcohol septal ablation to frame a discussion of modern therapies for hypertrophic cardiomyopathy. The current treatment landscape includes medications, both old and new, and surgical and procedural interventions to relieve mechanical obstruction. Several promising new modalities for relieving obstruction are in the nascent stages of development.

Outcome Of Corynebacterial Bloodstream Infection In Patients With Cardiac Implantable Electronic Devices: A Brief Report And Systematic Review, Supavit Chesdachai, Larry M Baddour, M Rizwan Sohail, Bharath Raj Palraj, Malini Madhavan, Hussam Tabaja, Michele T Mcginnis, Madiha Fida, Douglas W Challener, Daniel C Desimone

Faculty, Staff and Students Publications

Cardiac implantable electronic device infection in the context of corynebacterial bloodstream infection (BSI) remains poorly understood. From 2012 to 2023 at Mayo Clinic, 4 of 12 patients with corynebacterial BSI had cardiac implantable electronic device infection: 1 patient was diagnosed during a relapsing BSI episode. Undefined source, persistent BSI, and the presence of a prosthetic cardiac valve were common characteristics.

Detection Of Soil-Transmitted Helminths And Schistosoma Spp By Nucleic Acid Amplification Test: Results Of The First 5 Years Of The Only International External Quality Assessment Scheme, Annemiek H J Schutte, Rob Koelewijn, Sitara S R Ajjampur, Bruno Levecke, James S Mccarthy, Rojelio Mejia, Steven A Williams, Jaco J Verweij, Lisette Van Lieshout, Jaap J Van Hellemond

Faculty, Staff and Students Publications

BACKGROUND: Infections with soil-transmitted helminths (STH) and schistosomiasis (SCH) result in a significant global health burden, particularly in rural communities in low and middle-income countries. While microscopy remains the primary diagnostic method for STH and SCH in resource-limited settings, nucleic acid amplification tests (NAATs) are gaining prominence as tools for evaluation of public health control programs in endemic countries, and individual diagnosis in high-income countries. Despite the high sensitivity and specificity of NAATs, previous research has highlighted inter-laboratory variations, both in technical and clinical performance, justifying the need for continuous proficiency testing.

METHODOLOGY: Results from 5 rounds over a 5-year …

Low Vitamin D Levels In Patients With Symptoms Of Gastroparesis: Relationships With Nausea And Vomiting, Gastric Emptying And Gastric Myoelectrical Activity, Kenneth L Koch, Henry P Parkman, Katherine P Yates, Mark L Van Natta, Madhusudan Grover, Gianrico Farrugia, Thomas L Abell, Richard W Mccallum, Irene Sarosiek, Braden Kuo, Robert J Shulman, Laura Miriel, James Tonascia, Pankaj J Pasricha

Faculty, Staff and Students Publications

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and …

Unraveling The Complex Dynamics Of Cardiac Fibrosis: Ccn1 As A Novel Regulator Of Scar Collagen Architecture And Structural Integrity In Myocardial Infarction., Annalara Garland Fischer

Electronic Theses and Dissertations

Expansion of the extracellular matrix (ECM), known as fibrosis, accompanies nearly all forms of cardiac disease; however, its most significant and complex manifestations arise following a myocardial infarction (MI). This process, principally led by fibroblasts, constitutes a necessary and adaptive response acutely to fill the void from cardiomyocyte necrosis following ischemic injury due to the heart’s lack of regenerative capacity. This acute response never fully resolves and contributes to ongoing collagen accumulation in non-infarcted regions, leading to diminished ventricular compliance, ongoing myocyte loss, and attrition in function—culminating in heart failure. Further, recent research demonstrates that concomitant with progressive increases in …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

Covid-19 Infection And Mortality, Patient Comorbidities, Social Determinants Of Health, And Environmental Influences In Kentucky., Shaminul Hoque Shakib

Electronic Theses and Dissertations

OBJECTIVES: To investigate patient- and county-level disparities in COVID-19-related mechanical ventilation use and mortality by SDOH factors and comorbidities among Medicaid non-pregnant adult beneficiaries in Kentucky. Additionally, to compare the association of COVID-19-related infections and mortality with social mobility and weather between Indiana and Kentucky during the stay-at-home period (March 1 to May 15, 2020). METHODS: In chapter 2, an administrative claims-based retrospective cohort study was conducted using the Kentucky Health Facility and Services database. Medicaid beneficiaries who were hospitalized during 2020–2021 in Kentucky were considered in the logistic regression and the Cox regression model to estimate the risk of …

Trends In Central Nervous System-Active Polypharmacy Among People With Multiple Sclerosis, Hayden Naizer, Joseph Wozny, Trudy Millard Krause, Ethan Huson, Leorah Freeman

Faculty, Staff and Student Publications

BACKGROUND: People with multiple sclerosis (pwMS) are at risk of concurrently using multiple central nervous system (CNS)-active drugs, yet the prevalence of CNS-active polypharmacy remains unmeasured in pwMS.

OBJECTIVE: The objective is to measure the prevalence of CNS-active polypharmacy in pwMS.

METHODS: This serial, cross-sectional study measured CNS-active polypharmacy in people with MS in the United States from 2008 to 2021 using insurance claims data. CNS-active polypharmacy was defined as the concurrent prescription of ⩾3 CNS-active drugs for >30 continuous days. CNS-active drugs included antidepressants, antiepileptics, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, opioids, and skeletal muscle relaxants.

RESULTS: The …

Differences In Bilinguals And Multilinguals Diagnosed With Alzheimer's Disease, Nathalie Rios Carreon

University Honors Theses

Alzheimer’s Disease does not have a cure but there are different things that can be done to manage the disease. Keeping your brain healthy is important to keep cognitive reserve (CR) strong and intact. One way to keep CR intact is to speak more than one language. Previous research done shows that monolinguals typically get diagnosed with Alzheimer's disease 4 to 5 years earlier than bilinguals and multilinguals. Using existing articles it was found that this new research was similar to research already done. Speaking more than one language keeps the brain healthy in many different ways. Research suggests that …

Enolase Inhibitors As Therapeutic Leads For Naegleria Fowleri Infection, Jillian E Milanes, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian N Dominy, Daniel C Whitehead, Steven W Millward, Madison Bolejack, Roger Shek, Logan Tillery, Isabelle Q Phan, Bart Staker, E Ashley Moseman, Xiang Zhang, Xipeng Ma, Audriy Jebet, Xinmin Yin, James C Morris

Faculty, Staff and Student Publications

Infections with the pathogenic free-living amoebae Naegleria fowleri can lead to life-threatening illnesses including catastrophic primary amoebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen. Recently, human enolase 2 (ENO2) phosphonate inhibitors have been developed as lead agents to treat glioblastoma multiforme (GBM). These compounds, which cure GBM in a rodent model, are well-tolerated in mammals because enolase 1 (ENO1) is the predominant isoform used …

Delineating Metastasis In Mss Colorectal Cancer By Single - Cell Rna Sequencing, Shuangjie You

Dissertations and Theses (Open Access)

Colorectal cancer Colorectal Cancer (CRC) is the leading cause of cancer-related deaths, with the majority of these deaths occurring after metastases. In this study, we used single-cell RNA transcriptome sequencing to characterize the cellular and molecular features of primary CRC and colorectal liver metastases (CRLM). Analysis of 130 samples revealed significant heterogeneity in the tumor microenvironment (TME) characterized by a diversity of cancer-associated fibroblasts, immune cells, and endothelial cell populations. Notably, we identified different CAF subtypes, including inflammatory (iCAFs), matrix(mCAFs), complement (cCAFs), and vascular (vCAFs). iCAFs were enriched in primary tumors expressing higher levels of inflammation-associated genes, whereas mCAFs were …

Exploring The Role Of The Arginine-Methylation Writer-Reader Pair Prmt5/Snd1 In Jak2-Mutant Myeloproliferative Neoplasms, Rocio Rubiano

Dissertations and Theses (Open Access)

Myeloproliferative neoplasms (MPNs) are a hematopoietic disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the JAK-STAT signaling pathway. A role for the methyltransferase activity of Protein Arginine Methyltransferase 5 (PRMT5) has been proposed in JAK2-mutant MPN, highlighting both a mechanism through which this mutation can drive disease progression and a potential mode of therapeutic intervention. Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) is the effector molecule responsible …

Genetic Analysis Of Kmt2d Loss In Tumorigenesis Using Genetically Engineered Mouse Models, Yingda Jiang

Dissertations and Theses (Open Access)

The Cancer Genome Atlas Program (TCGA) has discovered multiple tumor suppressors that are commonly mutated across a variety of human cancers, such as chromatin regulators in COMPASS and SWI/SNF complexes. KMT2D, a histone H3K4 methyltransferase in the COMPASS complex, is frequently mutated in human lymphoma, melanoma, and epithelial carcinoma. Biochemically, KMT2D shapes the cellular enhancer landscape as the major writer of the putative enhancer mark H3K4me1. Given the critical role of cellular enhancer landscape in determining cellular lineage in embryonic development, it is unknown whether enhancer dysregulation caused by KMT2D loss leads lineage switch of tumor cells, which has …