Medicine and Health Sciences Commons^™

Current Ecotoxicity Testing Needs Among Selected U.S. Federal Agencies, Patricia Ceger, Natalia Garcia-Reyero Vinas, David Allen, Elyssa Arnold, Raanan Bloom, Jennifer C. Brennan, Carol Clarke, Karen Eisenreich, Kellie Fay, Jonathan Hamm, Paula F.P. Henry, Katherine E. Horak, Wesley Hunter, Donna Judkins, Patrice Klein, Nicole Kleinstreuer, Kara Koehrn, Carlie A. Lalone, James P. Laurenson, Jessica K. Leet, Anna Lowit, Scott G. Lynn, Teresa Norberg-King, Edward J. Perkins, Elijah J. Petersen, Barnett A. Rattner, Catherine S. Sprankle, Thomas Steeger, Jim E. Warren, Sarah Winfield, Edward Odenkirchen

United States Department of Agriculture Wildlife Services: Staff Publications

U.S. regulatory and research agencies use ecotoxicity test data to assess the hazards associated with substances that may be released into the environment, including but not limited to industrial chemicals, pharmaceuticals, pesticides, food additives, and color additives. These data are used to conduct hazard assessments and evaluate potential risks to aquatic life (e.g., invertebrates, fish), birds, wildlife species, or the environment. To identify opportunities for regulatory uses of non-animal replacements for ecotoxicity tests, the needs and uses for data from tests utilizing animals must first be clarified. Accordingly, the objective of this review was to identify the ecotoxicity test data …

Defining An Epidemiological Landscape That Connects Movement Ecology To Pathogen Transmission And Pace-Of-Life, Kezia Manlove, Mark Wilber, Lauren White, Guillaume Bastille-Rousseau, Anni Yang, Marie L.J. Gilbertson, Meggan E. Craft, Paul C. Cross, George Wittemyer, Kim M. Pepin

United States Department of Agriculture Wildlife Services: Staff Publications

Pathogen transmission depends on host density, mobility and contact. These components emerge from host and pathogen movements that themselves arise through interactions with the surrounding environment. The environment, the emergent host and pathogen movements, and the subsequent patterns of density, mobility and contact form an ‘epidemiological landscape’ connecting the environment to specific locations where transmissions occur. Conventionally, the epidemiological landscape has been described in terms of the geographical coordinates where hosts or pathogens are located. We advocate for an alternative approach that relates those locations to attributes of the local environment. Environmental descriptions can strengthen epidemiological forecasts by allowing for …

Unresectable Primary Tracheal Synovial Sarcoma, Joann M. Butkus, Mackenzie Kramer, Daniel Eichorn, Ali Raza R. Shaikh, Rajesh R. Patel

Otolaryngology (ENT) Resident Research

Synovial sarcoma (SS) comprises less than 1% of head and neck cancers, and less than five cases of adult primary tracheal SS have been described. This case describes a patient encountered at a community-based academic hospital, and retrospective chart review was performed for data collection. A woman in her forties presented with shortness of breath due to a superior mediastinal mass found to be an unresectable primary tracheal SS. Primary treatment resorted to curative-intent radiation therapy. Subsequent metastasis required systemic chemotherapy with pazopanib. To the best of our knowledge, this is the first reported case of this nature and adds …

A Survey Of Stroke-Related Capabilities Among A Sample Of Us Community Emergency Departments, Kori S Zachrison, Latha Ganti, Dhruv Sharma, Pawan Goyal, Marquita Decker-Palmer, Opeolu Adeoye, Joshua N Goldstein, Edward C Jauch, Bruce M Lo, Tracy E Madsen, William Meurer, John A Oostema, Cindy Mendez-Hernandez, Arjun K Venkatesh

2020-Current year OA Pubs

Objectives: Most acute stroke research is conducted at academic and larger hospitals, which may differ from many non-academic (ie, community) and smaller hospitals with respect to resources and consultant availability. We describe current emergency department (ED) and hospital-level stroke-related capabilities among a sample of community EDs participating in the Emergency Quality Network (E-QUAL) stroke collaborative.

Methods: Among E-QUAL-participating EDs, we conducted a survey to collect data on ED and hospital stroke-related structural and process capabilities associated with quality of stroke care delivery and patient outcomes. EDs submitted data using a web-based submission portal. We present descriptive statistics of self-reported capabilities. …

Quantile Differences In The Age-Related Decline In Cardiorespiratory Fitness Between Sexes In Adults Without Type 2 Diabetes Mellitus In The United States, Andrew Ortaglia, Melissa Stansbury, Michael David Wirth, Xuemei Sui, Matteo Bottai

Faculty Publications

Objective: To comprehensively assess the extent to which the decline in cardiorespiratory fitness (CRF) with age differs between sexes. Participants and Methods: This study used data from the Aerobics Center Longitudinal Study, conducted between September 1974 and August 2006, consisting primarily of White adults from middle-to-upper socioeconomic strata restricted to adults without type 2 diabetes mellitus (33,742 men and 9,415 women). Quantile regression models were used to estimate the differences in age-associated changes in CRF between the sexes, estimated using a maximal treadmill test. Results: For adults aged up to 45 years, significant differences in slopes relating to age and …

Role Of Type 4 Phosphodiesterases In Thermoregulation And Salivation In Mice, Abigail Grace Boyd

Graduate Theses and Dissertations (2019 - present)

Type 4 cAMP phosphodiesterases (PDE4s) comprise a family of four isoenzymes, PDE4A to D, that hydrolyze and inactivate the second messenger cAMP. Non/PAN selective PDE4 inhibitors, which inhibit all four subtypes simultaneously, produce many promising therapeutic benefits, such as anti-inflammatory or cognition- and memory-enhancing effects. However, unwanted side effects, principally, nausea, diarrhea, and emesis, have long hampered their clinical and commercial success. Targeting individual PDE4 subtypes has been proposed for developing drugs with an improved safety profile, but which PDE4 subtype(s) is/are actually responsible for nausea and emesis remains ill defined. In mice treated with PAN-selective inhibitors, there is substantial …

A Systematic Review And Meta-Analysis On Prevalence Of And Risk Factors Associated With Depression, Anxiety And Insomnia In Infectious Diseases, Including Covid-19: A Call To Action, Kai Yuan, Yong-Bo Zheng, Yi-Jie Wang, Yan-Kun Sun, Yi-Miao Gong, Yue-Tong Huang, Xuan Chen, Xiao-Xing Liu, Yi Zhong, Si-Zhen Su, Nan Gao, Yi-Long Lu, Zhe Wang, Wei-Jian Liu, Jian-Yu Que, Ying-Bo Yang, An-Yi Zhang, Meng-Ni Jing, Chen-Wei Yuan, Na Zeng, Michael V Vitiello, Vikram Patel, Seena Fazel, Harry Minas, Graham Thornicroft, Teng-Teng Fan, Xiao Lin, Wei Yan, Le Shi, Jie Shi, Thomas Kosten, Yan-Ping Bao, Lin Lu

Children’s Nutrition Research Center Staff Publications

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, …

State-Of-The-Art Review: Evidence On Red Meat Consumption And Hypertension Outcomes, Tara Shrout Allen, Harpreet S Bhatia, Alexis C Wood, Shabnam R Momin, Matthew A Allison

Children’s Nutrition Research Center Staff Publications

Hypertension (HTN) is a well-established risk factor for cardiovascular diseases (CVDs), including ischemic heart disease, stroke, heart failure, and atrial fibrillation. The prevalence of HTN, as well as mortality rates attributable to HTN, continue to increase, particularly in the United States and among Black populations. The risk of HTN involves a complex interaction of genetics and modifiable risk factors, including dietary patterns. In this regard, there is accumulating evidence that links dietary intake of red meat with a higher risk of poorly controlled blood pressure and HTN. However, research on this topic contains significant methodological limitations, which are described in …

Mobile Health With Head-Worn Devices: Challenges And Opportunities, Andrea Ferlini, Dong Ma, Lorena Qendro, Cecilia Mascolo

Research Collection School Of Computing and Information Systems

Monitoring human behavior and health status using mobile devices, a.k.a. Mobile Health, has gained increasing attention from both academia and industry in recent years. It allows imperceptible health tracking from the users and remote health management from the healthcare service providers. Headworn devices, such as earbuds, glasses, and BCIs (Brain Computer Interfaces), exhibit great potential for mobile health due to their advantageous wearing position, the human head, which is motion-resilient and full of human bio-signals. Although initial attempts have been conducted for different healthcare applications with head-worn devices, this fast-growing area is still under-explored and retains great promises. With this …

Twist1 Interacts With Β/Δ-Catenins During Neural Tube Development And Regulates Fate Transition In Cranial Neural Crest Cells, Jessica W Bertol, Shelby Johnston, Rabia Ahmed, Victoria K Xie, Kelsea M Hubka, Lissette Cruz, Larissa Nitschke, Marta Stetsiv, Jeremy P Goering, Paul Nistor, Sally Lowell, Hanne Hoskens, Peter Claes, Seth M Weinberg, Irfan Saadi, Mary C Farach-Carson, Walid D Fakhouri

Faculty, Staff and Student Publications

Cell fate determination is a necessary and tightly regulated process for producing different cell types and structures during development. Cranial neural crest cells (CNCCs) are unique to vertebrate embryos and emerge from the neural plate borders into multiple cell lineages that differentiate into bone, cartilage, neurons and glial cells. We have previously reported that Irf6 genetically interacts with Twist1 during CNCC-derived tissue formation. Here, we have investigated the mechanistic role of Twist1 and Irf6 at early stages of craniofacial development. Our data indicate that TWIST1 is expressed in endocytic vesicles at the apical surface and interacts with β/δ-catenins during neural …

Memory Reconsolidation: The Common Mechanism In Successful Treatment Of Trauma?, Gregory P. Brown

Psychiatry & Behavioral Health Faculty Research

Ubiquitous phenomenon in biological creatures which have memory or can learn, from mollusks to rats to humans. Some Affected Learning Types: procedural and motor skill memory, operant conditioning, declarative memory, episodic memory, classical fear conditioning, memory for cue-triggered heroin cravings. So what is it?

Memory Consolidation:

- the process of “synaptic consolidation”

- a memory or learning is initially unstable, but over time or repetition becomes stable in long term memory

- example is Classical Conditioning

The Utilization Of Stress Management In Critical Care Nurses To Decrease Nursing Burnout, Danny Atkins

Student Scholarly Projects

Practice Problem: Since COVID-19, nurses have felt the pressure from the pandemic on their shoulders. The practice problem has helped nurses manage stressors to decrease the symptoms of burnout.

PICOT: In critical care nurses (P), how does the implementation of HeartMath techniques for stress management (I) compared to standard practice (C) affect rates of absenteeism, request for assignment transfer, and resignations (O) over 8-weeks (T)?

Evidence: The evidence that guided this project change is based on the Johns Hopkins nursing evidenced-based-practice model.

Intervention: The intervention assisted critical care nurses in dealing with stress and fatigue by …

Unusual Presentation Of Multisystemic Inflammatory Syndrome, Farah Ebrahim, George Moturi, Newnex Mongare, Reena Shah

Internal Medicine, East Africa

COVID-19 pneumonia in children presents with very mild symptoms through an entity of multisystem inflammatory syndrome and can result in a life-threatening hyperinflammatory condition, with involvement of at least four organ systems and a marked inflammatory state. We present an 18-year-old high school student who presented with a sore throat, macular rash, abdominal pain, diarrhea, fevers, and joint pains. He presented with acute kidney injury and confusion with multiple tests and was eventually diagnosed with multisystem inflammatory syndrome in children (MIS-C).

The Burden And Characteristics Of Hiv-Infected Covid-19 Patients At A Tertiary Care Hospital In Sub-Saharan Africa—A Retrospective Cohort Study, Alok Iyer, Jasmit Shah, Reena Shah

Internal Medicine, East Africa

Background: After the first case of COVID-19 caused by the novel SARS-CoV-2 virus was discovered in Wuhan, China, in December 2019, the disease spread viciously throughout the world. Little is known about the impact of HIV infection on the clinical outcomes of patients co-infected with SARS-CoV-2. Studying the characteristics and outcomes of COVID-19 among HIV-positive patients is key to characterising the risk of morbidity and mortality of HIV-positive patients from COVID-19.

Methods: In this retrospective cohort study, we included patients admitted to Aga Khan University Hospital, Nairobi, with laboratory-confirmed COVID-19 infection and who had consented to HIV screening. We compared …

A Genome-Wide Association Study Of Obstructive Heart Defects Among Participants In The National Birth Defects Prevention Study, Sara R Rashkin, Mario Cleves, Gary M Shaw, Wendy N Nembhard, Eirini Nestoridi, Mary M Jenkins, Paul A Romitti, Xiang-Yang Lou, Marilyn L Browne, Laura E Mitchell, Andrew F Olshan, Kevin Lomangino, Sudeepa Bhattacharyya, John S Witte, Charlotte A Hobbs

Faculty, Staff and Student Publications

Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (N

Insights From A Large-Scale Whole-Genome Sequencing Study Of Systolic Blood Pressure, Diastolic Blood Pressure, And Hypertension, Tanika N Kelly, Xiao Sun, Karen Y He, Michael R Brown, Sarah A Gagliano Taliun, Jacklyn N Hellwege, Marguerite R Irvin, Xuenan Mi, Jennifer A Brody, Nora Franceschini, Xiuqing Guo, Shih-Jen Hwang, Paul S De Vries, Yan Gao, Arden Moscati, Girish N Nadkarni, Lisa R Yanek, Tali Elfassy, Jennifer A Smith, Ren-Hua Chung, Amber L Beitelshees, Amit Patki, Stella Aslibekyan, Brandon M Blobner, Juan M Peralta, Themistocles L Assimes, Walter R Palmas, Chunyu Liu, Adam P Bress, Zhijie Huang, Lewis C Becker, Chii-Min Hwa, Jeffrey R O'Connell, Jenna C Carlson, Helen R Warren, Sayantan Das, Ayush Giri, Lisa W Martin, W Craig Johnson, Ervin R Fox, Erwin P Bottinger, Alexander C Razavi, Dhananjay Vaidya, Lee-Ming Chuang, Yen-Pei C Chang, Take Naseri, Deepti Jain, Hyun Min Kang, Adriana M Hung, Vinodh Srinivasasainagendra, Beverly M Snively, Dongfeng Gu, May E Montasser, Muagututi'a Sefuiva Reupena, Benjamin D Heavner, Jonathon Lefaive, James E Hixson, Kenneth M Rice, Fei Fei Wang, Jonas B Nielsen, Jianfeng Huang, Alyna T Khan, Wei Zhou, Jovia L Nierenberg, Cathy C Laurie, Nicole D Armstrong, Mengyao Shi, Yang Pan, Adrienne M Stilp, Leslie Emery, Quenna Wong, Nicola L Hawley, Ryan L Minster, Joanne E Curran, Patricia B Munroe, Daniel E Weeks, Kari E North, Russell P Tracy, Eimear E Kenny, Daichi Shimbo, Aravinda Chakravarti, Stephen S Rich, Alex P Reiner, John Blangero, Susan Redline, Braxton D Mitchell, Dabeeru C Rao, Yii-Der Ida Chen, Sharon L R Kardia, Robert C Kaplan, Rasika A Mathias, Jiang He, Bruce M Psaty, Myriam Fornage, Ruth J F Loos, Adolfo Correa, Eric Boerwinkle, Jerome I Rotter, Charles Kooperberg, Todd L Edwards, Gonçalo R Abecasis, Xiaofeng Zhu, Daniel Levy, Donna K Arnett, Alanna C Morrison, Samoan Obesity, Lifestyle, And Genetic Adaptations Study (Olaga) Group,‡ Nhlbi Trans-Omics For Precision Medicine Topmed) Consortium

Faculty, Staff and Student Publications

BACKGROUND: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.

METHODS: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.

RESULTS: Two blood pressure signals …

Use Of Active Video Games With Or Without Videoconferencing On Health Outcomes In Adolescent And Young Adult Cancer Survivors: A Systematic Review, Ursela Christopherson, Stephanie J Wells, Nathan Parker, Elizabeth J Lyons, Michael D Swartz, Anna Blozinski, Karen Basen-Engquist, Susan Peterson, Maria C Swartz

Faculty, Staff and Student Publications

PURPOSE: Adolescent and young adult (AYA) cancer survivors experience greater functional deficits compared to non-cancer peers or older survivors with a similar diagnosis. Physical activity (PA) is a key strategy for mitigating functional decline, and motivation and peer support are critical PA facilitators in AYA cancer survivors. Active video games (AVGs) may be a "gateway" method to promote PA. Further, integrating AVGs into group videoconferencing, a medium used by AYAs to socialize, can capitalize on peer support needed for PA motivation. Thus, we examined the use of AVGs and/or videoconferencing in PA interventions that included AYA survivors and the effect …

Absolute Quantification Of Tc-99m Activity Distributions Using A Planar Molecular Breast Imaging Commercial System, Benjamin P. Lopez

Dissertations and Theses (Open Access)

Molecular breast imaging (MBI) uses two dedicated-breast semiconductor detectors to visualize the preferential uptake of technetium-99m-sestamibi (^99mTc-sestamibi) by breast cancer cells relative to surrounding benign breast tissues. Clinically, MBI is used primarily as a supplementary tool to standard-of-care mammography because of its improved detection of breast cancers, especially in women with mammographically-dense breasts. Because of a lack of image corrections, MBI applications are currently limited to qualitative evaluations of relative pixel intensities between image regions with suspected lesions and normal tissue.

The objective of this dissertation was to use Monte Carlo simulations to better characterize the MBI imaging …

Perceptions And Roles Of Genetic Counselors In Perinatal Palliative Care: Where Are We Now?, Amanda Chamberlain

Dissertations and Theses (Open Access)

After the identification of a life-limiting fetal diagnosis, a perinatal palliative care (PPC) team can provide specialized medical care and emotional support for the family throughout the pregnancy and after delivery. Although the growth of the field of PPC over the last ten years is well-documented, there is only one study to date that explores the experiences of genetic counselors with regards to PPC. This study seeks to further the understanding of genetic counselors’ current perceptions of, experiences with, and roles in the delivery of PPC.

An edited version of the Perinatal Palliative Care Perceptions and Barriers Scale was used …

Unraveling The Effects Of Aerobic Exercise And Erk5 Signaling In The Solid Tumor Microenvironment Using Murine Models, Hannah Savage

Dissertations and Theses (Open Access)

Solid tumors are comprised of multiple cell types which communicate and work together to promote tumor progression. Advances in the treatment of solid tumors have armed clinicians with more efficacious pharmacologic agents and combinations. However, a focus on drug adjuvants in the treatment of solid cancer has left gaps in knowledge regarding non-pharmacologic treatment adjuvants, like aerobic exercise. The current dissertation investigates pharmacologic and non-pharmacologic based approaches to remodel the solid tumor microenvironment landscape and alter therapeutic efficacy. We disassemble compartments of the tumor microenvironment, including tumor vasculature and immune infiltrate, using mouse models and single cell techniques, to elucidate …

Development Of Graphical Models And Statistical Physics Motivated Approaches To Genomic Investigations, Yashwanth Lagisetty

Dissertations and Theses (Open Access)

Identifying genes involved in disease pathology has been a goal of genomic research since the early days of the field. However, as technology improves and the body of research grows, we are faced with more questions than answers. Among these is the pressing matter of our incomplete understanding of the genetic underpinnings of complex diseases. Many hypotheses offer explanations as to why direct and independent analyses of variants, as done in genome-wide association studies (GWAS), may not fully elucidate disease genetics. These range from pointing out flaws in statistical testing to invoking the complex dynamics of epigenetic processes. In the …

Bhlhe40: Required For Tumor Microenvironment Remodeling And Immune Checkpoint Therapy Efficacy, Avery Salmon, Avery J. Salmon

Dissertations and Theses (Open Access)

Advancements in immunotherapy treatments have become essential in the treatment of various cancers, such as those with high tumor burden like melanoma(Brahmer et al., 2012; Hodi et al., 2010). Immunotherapy, specifically immune checkpoint therapy (ICT) provides antagonist effect on specific immune checkpoints to control effector T cell functions(Pardoll, 2012). This therapy allows for the modulation of anti-tumor responses through the use of monoclonal antibodies, such as anti-CTLA-4 or anti-PD-1 that block the receptors from binding with their ligands, thus allowing for CD4⁺ and CD8⁺ T cell priming and activation(Wei et al., 2017). However, the required epigenetic and transcriptional …

Cell-Free Dna Sequencing In Multiple Myeloma, Russell Irwin

Dissertations and Theses (Open Access)

Multiple myeloma (MM) is an incurable plasma cell dyscrasia. Recent advances in MM therapy, including CAR-T therapy, have increased survival and shown the value of assessing treatment response with great sensitivity, both in acute and long-term settings. Cell-free DNA, DNA fragments which are released into circulation as a part of normal cellular turnover, is a useful and dynamic biomarker in cancer patients due to the presence of circulating tumor DNA (ctDNA), which is readily identified using next generation sequencing. Here we report the analytical sensitivity, applicability, consistency, and prognostic ability of M5Seq, a novel hybrid capture panel designed for MM …

Development Of Advanced Mr-Guided Adaptive Radiation Therapy Methods For Head & Neck Cancers On The 1.5t Mr-Linac, Brigid Mcdonald

Dissertations and Theses (Open Access)

The 1.5T hybrid MRI/linear accelerator (MR-linac) has recently been introduced into clinical practice and used for the treatment of head and neck cancers (HNC). This device enables on-line adaptive radiation therapy (ART) based on anatomical changes throughout treatment and variations in patient position. This novel technology also has the potential for advanced ART strategies such as dose-optimized ART, in which the treatment plan is optimized based on the accumulated dose over previous fractions, or biological image-guided ART, in which the plan is adapted based on individual tumor response as measured through quantitative imaging techniques such as diffusion-weighted imaging (DWI). The …

Yap And Taz Are Required For Neural Crest-Derived Cardiovascular Development, Shannon Erhardt

Dissertations and Theses (Open Access)

Congenital heart defects (CHDs) are the most common human birth defect, occurring in ~1/100 newborns, and are a leading cause of early infant death. Cardiac neural crest cells (NCCs) are a migratory and multipotent cell population known to aid in the development of the cardiac outflow tract (OFT), valves, and interventricular septum, during embryogenesis. Yap and Taz are downstream effectors of the fundamental Hippo signaling pathway and are vital for proper organ and tissue development, yet their role in neural crest (NC)-derived heart formation is still largely unknown. We generated Yap and Taz conditional knockout (CKO) mice using a Cre-lox …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Roles Of Oxidative Stress And Dna Methylation In Cigarette Smoking-Induced Accelerated Acute Myeloid Leukemia Progression, Mary Figueroa

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is a commonly diagnosed cancer in smokers. When current or former smokers have AML, they have worse survival compared to never smoking patients. This has been observed clinically for decades, but then it is unknown how smoking leads to worsened AML survival. Smoking causes oxidative stress and altered DNA methylation that persists for decades in peripheral blood mononuclear cells, but these changes from smoking have not been evaluated in the context of AML. We hypothesize that smoking-induced molecular changes, including altered DNA methylation associated with poor AML prognosis, promote AML. We developed a novel model to …

Lipid Composition And Configuration Drive Biophysical Properties Of The Mammalian Plasma Membrane, Jessica L. Symons

Dissertations and Theses (Open Access)

In the 1970s, it was established that phospholipid (PL) classes are asymmetrically distributed across the (PM) leaflets. Recapitulating strategies coupled with newly developed, high-resolution shotgun lipidomics, our lab confirmed PL class asymmetry and surprisingly measured the endoplasmic leaflet to contain double the number of PLs vs. the exoplasmic leaflet. My re-analysis of classical studies show that PM PL abundance imbalance has been a consistent finding across decades of literature. This is surprising, because bilayers do not tolerate interleaflet area imbalances to the degree that this imbalance would suggest, which prompted us to consider the existence of an elusive membrane resident …

The Novel Role Of Dnmbp In Kidney Development, Brandy Walker

Dissertations and Theses (Open Access)

Congenital anomalies of the kidney and urinary tract (CAKUT) accounts for nearly one-fourth of all birth defects and more than 40% of pediatric end-stage renal disease, yet only 10-20% of CAKUT cases have a known monogenetic cause. Human kidneys are composed of up to a million epithelial tubules called nephrons. Disruption of nephron development is one of the many congenital anomalies that cause CAKUT, often resulting in chronic or end-stage renal disease which requires transplant. During nephron epithelialization, the formation of stable cadherin-mediated adhesion junctions is essential for maintaining cell-cell contacts. To understand the cell behaviors underlying abnormalities in renal …

Induced Cytotoxicity In Crebbp/Ep300mut Head And Neck Squamous Cell Carcinoma, Thomaia Pamplin

Dissertations and Theses (Open Access)

INDUCED CYOTOXICTY IN CREBBP/EP300mut HEAD AND NECK SQUAMOUS CELL CARCINOMA

Thomaia Pamplin

Advisor: Curtis Pickering, Ph.D.

Background: Head and neck squamous cell carcinoma HNSCC is the most common malignancy in the head and neck. Most cases are found in advanced stages and depending on the location can be treated with surgical resection and/or radiation (XRT), chemotherapy, or chemoradiation. Our lab groups have identified that HNSCC with a mutation in its CREBBP/EP300 genes can be sensitized to XRT when the histone acetyltransferase activity of CREBBP/EP300 is inhibited. This radiosensitization manifests in the form of increased cell death for …