Digital Commons Network^™

Fireproof: Intricacies Of Microglial Biology, Wei Cao

Faculty, Staff and Student Publications

No abstract provided.

Hypoglossal Neuropathy In The Pathogenesis Of Fibrosis-Related Late-Radiation Associated Dysphagia: A Correlative Analysis Utilizing Electromyography To Explore The Frequency Of Clinical And Subclinical Neuropathy In A Pilot Dysphagia Trial, Holly Mcmillan, Christine Okoro, Sheila Buoy, Karin Woodman, Nicolaas Anderson, Clifton Fuller, Stephen Y Lai, Katherine Hutcheson

Faculty, Staff and Student Publications

Background: Late radiation-associated dysphagia (late-RAD) commonly presents in patients with signs of hypoglossal neuropathy, with hallmark clinical features including lingual atrophy, deviation, and fasciculation. Gold-standard electromyography (EMG) has not been used to explore the frequency of hypoglossal neuropathy in patients with late-RAD.

Methods: Exploratory post hoc secondary analysis of MANTLE trial (NCT03612531) was completed. The presence of cranial nerve XII (CN XII) neuropathy was classified by (1) features of clinical assessment as well as (2) intramuscular genioglossus EMG pre-MANTLE intervention in disease-free HNC survivors ≥ 2 years post-radiotherapy (RT) with grade ≥ 2 fibrosis and dysphagia.

Results: All …

Acta2 Pathogenic Variants Activating Heat Shock Factor 1 And Increasing Cholesterol Biosynthesis In Smooth Muscle Cells Predispose To Early Onset Atherosclerosis, Maura L Boerio, Abhijnan Chattopadhyay, Xue-Yan Duan, Aamuktha Karla, Ernesto Calderon Martinez, Amelie Pinard, Andrew K Morse, Darshan Reddy, Sree Dharma, Walter Velasco-Torrez, Julien Marcadier, Siddharth K Prakash, Sherene Shalhub, Julie De Backer, Richmond Jeremy, Shaine A Morris, Anji T Yetman, Alan C Braverman, Dianna M Milewicz

Faculty, Staff and Student Publications

Background: ACTA2 pathogenic variants predispose to thoracic aortic disease, and a subset of variants lead to early onset atherosclerotic cardiovascular disease (ASCVD). The molecular pathway linking misfolded SMA (α-smooth muscle actin) monomers to augmented atherosclerosis-associated smooth muscle cell phenotypic modulation can be modeled in vitro by stably expressing the ACTA2 p.R149C variant in Acta2-/- smooth muscle cells.

Methods: The Montalcino Aortic Consortium patient registry was used to identify cases with ACTA2 pathogenic/likely pathogenic missense variants. These patients were surveyed, and medical records were reviewed, to identify cases with early onset ASCVD. The variants for these cases, as well as …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Modern Home Cooking Practices, The Role Of New Media, And Implications For Culinary Medicine: A Qualitative Study Among Mothers With Low Income, Margaret Raber, Maria Vazquez, Syeda Khan, Sahiti Myneni, Debbe Thompson

Faculty, Staff and Student Publications

Culinary medicine offers a practical, experiential approach to nutrition education, but in-person programs are resources intensive. Digital interventions may offer a scalable, acceptable approach to culinary medicine in populations that are at increased risk for poor diet, such as parents with low income. The purpose of this study was to examine modern home cooking behavior and the role of new media from the perspective of parents with low income and identify implications for culinary medicine research. Twenty parents from 6- to 11-year-old children that qualify for free/reduced school lunch programs completed a survey and interview examining online cooking information seeking …

Decellularized Extracellular Matrix Scaffolds To Engineer The Dormant Landscape Of Microscopic Colorectal Cancer Liver Metastasis, Sabrina N Vandenheuvel, Lucia L Nash, Abigail J Clevenger, Claudia A Collier, Oscar R Benavides, Sanjana Roy, Brinlee Goggans, Aelita Salikhova, Anvitha Tharakesh, Svasti Haricharan, Amber N Stratman, Scott Kopetz, Alex J Walsh, Shreya A Raghavan

Faculty, Staff and Student Publications

Recurrent liver-metastatic colorectal cancer contributes to high mortality. Recurrence occurs when dormant, microscopic residual disease survives initial treatment to escape dormancy. In their dormant, microscopic state within the liver, these metastatic lesions are undetectable by clinical diagnostic imaging until they form overt, chemoresistant metastases. Therefore, understanding the molecular mechanisms underlying dormancy in colorectal cancer liver metastases is a significant knowledge gap, motivating the engineering of nuanced in vitro models of disease. The current work presents an engineered model of liver-metastatic colorectal cancer dormancy. Decellularized extracellular matrix (dECM) scaffolds are used to provide microscopic colorectal cancer cell clusters with a biomimetic, …

Local Delivery Of Mir-27a* Using Ultrasound-Targeted Microbubble Cavitation Inhibits Squamous Cell Carcinoma Growth, Nikhil S Chari, Cheng Chen, Thiruganesh Ramasamy, Xucai Chen, Geetika Wadhwa, Anurag N Paranjape, Stephen Y Lai, Flordeliza S Villanueva

Faculty, Staff and Student Publications

Objective: Ultrasound-targeted microbubble (MB) cavitation (UTMC) is an image-guided therapeutic oligonucleotide delivery platform utilizing intravenously injected gas-filled ultrasound contrast agents, which carry the therapeutic on the MB shell. During transit of MBs in the microcirculation of target tissue, ultrasound causes MB oscillation, facilitating endocytosis-independent payload uptake within insonified cells. Here, we tested the hypothesis that UTMC-mediated miR-27a* delivery will reduce tumor growth rate and result in accumulation of miR-27a* within tumor cells and the tumor microenvironment.

Methods: We used UTMC to deliver miR-27a* to SCC-VII cells in vitro and in SCC-VII mouse tumor models. Pulsed ultrasound was delivered during intravenous …

Who Classification Of Skin Tumours: Key Updates In The Fifth Edition, Gabrielle Goldman-Lévy, Raymond Barnhill, Boris C Bastian, Werner Kempf, David Elder, Pedram Gerami, Wayne Grayson, Dmitry Kazakov, Daniela Massi, Jane Messina, Arnaud De La Fouchardière, Alexander J Lazar, Thomas Brenn, Brian Rous, Andrew Field, Anthony Gill, Jennelle C Hodge, Joseph D Khoury, Katia Leite, Shahin Sayed, Puay Hoon Tan, Rosalie Elenitsas, Eduardo Calonje, Lyn M Duncan, Liang Zhiyong, Holger Moch, Rajendra Singh, Harshima Wijesinghe, Ian Cree, Dilani Lokuhetty

Faculty, Staff and Student Publications

The 5th edition of the World Health Organization Classification of Tumours (WCT) serves as a foundation for global diagnostic standards in tumour pathology. Similar to other volumes in this series, the Skin Tumours (Skin5) edition follows a standardized approach. This edition introduces two new chapters: 'Tumours of the nail unit' and 'Metastases to skin', along with new entities across relevant chapters. This review article provides an overview of the updates in Skin5 based on currently published evidence, with emphasis on newly introduced chapters and newly described entities that involve the skin, in particular, epidermal, melanocytic and appendageal tumours.

Investigating The Oxygen Dependence Of Flash-Rt Using Electron Paramagnetic Resonance Imaging, Trey Waldrop, Grace Murley, Brett Velasquez, Elise Konradsson, Denae Neill, Luke Connell, Alan Lopez Hernandez, Abagail Delahoussaye, F William Schuler, Jorge De La Cerda, Ziyi Li, Mark D Pagel, Emil Schüler

Faculty, Staff and Student Publications

Purpose: The FLASH effect occurs when radiation given at ultra-high dose rates spares healthy tissue while achieving isoeffective tumor control relative to conventional (CONV) dose rate irradiation. Limited data has implicated oxygen in the FLASH effect. This study investigated the effect of tissue oxygen tension (pO2) on gastrointestinal (GI) FLASH sparing in mice.

Methods: pO2 was quantified in vivo by electron paramagnetic resonance imaging (EPRI)- noninvasive oximetry through spin probe injection and magnetic resonance co-registration- and a phosphorescent quenching microsensor. B6(Cg)-Tyrc-2 J/J female mice were imaged while breathing 10%, 21%, and 95% oxygen. C57BL/6 mice of both sexes underwent microsensor …

Tbr2-Dependent Parallel Pathways Regulate The Development Of Distinct Iprgc Subtypes, Takae Kiyama, Ching-Kang Chen, Halit Y Altay, Yu-Jiun Chen, Leviette Sigala, Dan Su, Steven Eliason, Brad A Amendt, Chai-An Mao

Faculty, Staff and Student Publications

The intrinsically photosensitive retinal ganglion cells (ipRGC) are the conduit between the retina and brain regions responsible for non-image-forming and image-forming vision. In mice, six ipRGC subtypes have been discovered based on morphological characteristics, functions, and molecular profiles. All ipRGCs arise from Tbr2-expressing RGCs during developmental stages and subsequently diverge and differentiate into the six mature, distinct subtypes in adult retinas. However, the cellular and molecular mechanisms controlling the formation and maturation of the six ipRGC subtypes remain elusive. Here, we demonstrate that two Tbr2-dependent transcription factors, Iroquois‑related homeobox 1 (Irx1) and T-box containing factor 20 (Tbx20), are key downstream …

Neurological Recovery After Ich Is Mediated By The Aryl Hydrocarbon Receptor-Bilirubin Interplay Through Improved Erythrophagocytosis, Xiurong Zhao, Shun-Ming Ting, Guanghua Sun, Jaroslaw Aronowski

Faculty, Staff and Student Publications

Hematoma clearance after ICH is a pro-hemostatic process aiming at repair/recovery and is achieved through microglia/macrophages (MMΦ)-mediated erythrophagocytosis. Upon the engulfment of masses of erythrocytes and toxic hemolysis products, hemoglobin and heme, phagocytes convert them to bilirubin (BrB). Bilirubin is essentially not soluble in water and when overproduced, it precipitates within the cell causing injury. Thus, keeping bilirubin soluble and at a low intracellular level is needed for proper function of MMΦ. Here, using cultured microglia (MG), we found that intracellular formation of BrB in microglia during erythrophagocytosis coincides with the activation of transcription factor AhR, and AhR target genes …

Study Of Nano-Bio Interactions In Biological Fluids: Modelling And Simulations., Beatrice Cipriani

Doctoral

Nanoparticles have attracted significant interest due to their tunable properties and unique physicochemical characteristics, offering promising applications in drug delivery, biosensing, and diagnostics. Their use in medicine has the potential to reshape current paradigms by enabling more efficient, precise, and patient-centric approaches. Although advances in nanomaterial synthesis have rapidly expanded the library of available nanodevices, our understanding of the mechanisms that govern their behaviour at biological interfaces remains limited. Nanoparticles are similar in size to biomolecules found in biological environments, leading to complex, competitive interactions that affect their functional performance, biological fate, and acquired bioidentity. Unlike traditional small molecules, which …

Pair-Feeding Study Designs Can Create Biases And Inflate Type I Error Rates: A Simulation Study, Wasiuddin Najam, Daniel E Kpormegbey, Deependra K Thapa, Bret Rust, Lilian Golzarri-Arroyo, Lance H Baumgard, Louis Wai-Tong Fan, Joseph G Ibrahim, Edith J Mayorga, David B Allison

Children’s Nutrition Research Center Staff Publications

Objective: Pair-feeding is a study design element where one group's food intake is provided to another group to assess whether a treatment effect is independent of food intake. Investigators often assume equivalent food intake across experimental conditions and exclude it from the statistical analysis. However, the impact of this practice on type I error (T1Er) rates has not been quantified.

Methods: We conducted a Monte Carlo simulation in which animals were assigned baseline weights and food intakes, then randomized to non-pair-fed or pair-fed groups. Daily food intake for both groups was initially drawn from the baseline food intake distribution. For …

Enteral And Intravenous Supplementation Of Arginine And Citrulline Fail To Prevent Necrotizing Enterocolitis In Preterm Neonatal Pigs, Caitlin Vonderohe, Julia Garcia Mancebo, Valeria Melendez Hebib, Barbara Stoll, Inka Didelija, Sarah Elefson, Mahmoud Mohammad, Brooklynn Earls, Greg Guthrie, Doug Burrin

Children’s Nutrition Research Center Staff Publications

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants with a morality rate that approaches 50%. Arginine has been widely studied in the field of clinical nutrition as a supplement for patients experiencing critical illness because it can be metabolized into nitric oxide, an important agent for supporting immunity and microcirculation. Citrulline has received less attention but can be metabolized into arginine and has a much longer plasma half-life than arginine. We used the highly translational preterm pig model to determine the effect of intravenous and enteral supplementation of arginine and citrulline on NEC incidence in …

Bet Inhibitor-Based Combinations Targeting Novel Dependencies In Mecom-Rearranged (R) Aml, Christine E Birdwell, Warren Fiskus, Christopher P Mill, Tapan M Kadia, Naval Daver, Courtney D Dinardo, Koji Sasaki, John A Davis, Kaberi Das, Hanxi Hou, Antrix Jain, Anna Malovannaya, Lauren B Flores, Rasoul Pourebrahim, Selina Yuan, Xiaoping Su, Michele Ceribelli, Kapil N Bhalla

Faculty, Staff and Student Publications

MECOM rearrangement in AML involves either inv(3)(q21;q26.2) or t(3;3)(q21;q26.2), where the dislocated GATA2 enhancer drives overexpression of the transcriptional regulator EVI1, causes concomitant GATA2 repression, and promotes AML progression, aggressive phenotype and therapy refractoriness. Treatment with BET protein inhibitor (BETi) induces in vitro and in vivo efficacy in MECOM-r AML cells. Utilizing an unbiased, high-throughput drug screen, focused on mechanistically-annotated drugs, we identified BRD4, PIK3CA, mTOR, BCL-xL and XIAP as dependencies in the MECOM-r AML cells. Monotherapy with mivebresib (BETi), dactolisib (PI3K/mTORi) and LCL161 (IAPi) dose-dependently induced greater lethality in PD MECOM-r versus non-MECOM-r AML cells. RNA-Seq and/or mass spectrometry …

Life-Extending Interventions Do Not Necessarily Result In Compression Of Morbidity: A Case Example Offering A Robust Statistical Approach, Deependra K Thapa, Wasiuddin Najam, Erik S Parker, Xi Rita Wang, Daniel L Smith, Ufuk Beyaztas, James F Nelson, Steven N Austad, Gary A Churchill, David B Allison

Children’s Nutrition Research Center Staff Publications

Despite extensive research on life-extending interventions, rigorous statistical techniques to determine their impact on compression of morbidity (CoM) are rarely used. We present a case example of an analytical method for examining the effect of life-extending dietary interventions on CoM by comparing the rates of decline in vitality and survival toward the end of life. Using data from previous experimental studies in mice, we calculated the average rate of vitality decline by fitting exponential decay models to individual vitality trajectories and compared this rate with the rate of survival decline estimated from Cox proportional hazards model. The results showed that, …

A Typology Of Australian Terrestrial Bird Communities, Martine Maron, Karlina Indraswari, Jonathan Mills-Anderson, Courtney B. Melton, Hugh Possingham, James Radford, April E. Reside, Andrew Bennett, Allan Burbidge, Michael Clarke, Rohan H. Clarke, Robert Davis, Teresa Eyre, Amanda Freeman, Michelle Gibson, Birgita Hansen, Jacinta Humphrey, Nigel Jackett, Bryony Palmer, Alex Kutt, Nicholas P. Leseberg, Richard Loyn, Alex Maisey, Golo Maurer, Helen Mayfield, Paul Mcdonald

Research outputs 2022 to 2026

Aim: Holistic measurement of the response of fauna communities to interventions requires suitable community condition metrics. However, the development of such metrics is hindered by the absence of broad-scale typologies at suitable spatial and ecological resolutions. We aimed to derive a preliminary typology of terrestrial bird communities for Australia, based on bird co-occurrence data, and describe and map the likely distribution of each community type across the continent. Location: Mainland Australia, continental islands. Time Period: 1973–2022. Major Taxa Studied: Aves. Methods: We used fine-scale co-occurrence data from standard 2-ha surveys in BirdLife Australia's citizen-science database. After filtering to reduce bias, …

Animal Taxa Threatened By Adverse Fire Regimes In Western Australia: A Synthesis And Outlook, Tim S. Doherty, Mark G. Allen, Karlene Bain, Stephen J. Beatty, Allan H. Burbidge, Renee A. Catullo, Sarah Comer, Ben Corey, Saul J. Cowen, Robert A. Davis, Martin A. Dziminski, J. Anthony Friend, Bruce Greatwich, Mark S. Harvey, Hannah Killian, Michael W. Klunzinger, Damian C. Lettoof, Nicola J. Mitchell, Melinda Moir, Harry A. Moore, David L. Morgan, Ian J. Radford, Michael G. Rix, Tom Vigilante, Adrian F. Wayne, Corey Whisson

Research outputs 2022 to 2026

Adverse fire regimes threaten biodiversity, potentially leading to population declines and increased extinction risk. Understanding how varying fire regimes affect threatened species is essential for effective ecosystem management, including in Western Australia where diverse ecosystems are exposed to wildfires, Indigenous burning, and prescribed fire. We compiled and synthesised data on the threat of adverse fire regimes to threatened animal taxa in Western Australia. Using a threat classification scheme, we ranked adverse fire regimes as having either no, low, medium, high, or unknown impact on each taxon. A total of 212 taxa were reviewed, 153 (72%) of which are considered fire-threatened: …

Mechanical Characterization And Modeling Of Rat Myocardia Under The Influence Of Epirubicin, Abdallah Mahmoud Alkhaiyat

Theses and Dissertations

Cancer remains a predominant health challenge that is responsible for a significant portion of global morbidity and mortality. Epirubicin (EPI), a chemotherapeutic anti-cancer drug, has shown remarkable efficacy in combating various malignancies. However, it is known to have undesirable side effects on the heart, collectively referred to as cardiotoxicity. This research investigates the adverse effects of chemotherapy on cardiac contractility through an in vitro examination of the mechanics of healthy and infarcted animal heart tissues. Electrically stimulated slices of rat ventricular tissue were tested using an isometric force measurement tissue bath. The tissue slices were subjected to uniaxial stretching, allowing …

Economic Impacts Of Abolishing Vertical Integration In The Us Pork Industry, Konstantinos Giannakas

Department of Agricultural Economics: Presentations, Working Papers, and Gray Literature

This paper develops a multi-market framework of analysis of vertical relationships in pork production and game theoretic models of heterogeneous firms to examine the economic, market and welfare impacts of abolishing vertical integration in the US pork sector. Different scenarios on the causes of vertical integration and the potential states of nature that can emerge after the removal of this vertical market arrangement are considered within this framework. Analytical results are consistent across the different scenarios and forms of strategic interactions between pork producers and indicate that the abolishment of vertical integration in the US pork sector will hurt pork …

Fighting The Black Snake: The Dapl And The Case For Indigenous Environmental Stewardship, Kenny Moll

Student Theses 2015-Present

This thesis analyzes the current scope of environmental injustice on Native lands in the U.S. Specifically it examines The Dakota Access Pipeline (DAPL) and its impacts on the Standing Rock Sioux Tribe of North Dakota. Western colonialism and capitalism have dominated North American ecosystems since their forcible introduction hundreds of years ago, causing the commodification of natural resources and leading to injustices such as that of the “Black Snake.” However, the story of The Standing Rock Sioux Tribe’s resistance will be analyzed through the framework of Indigenous philosophy and environmental justice. Chapter 1 analyzes the implementation of the DAPL and …

A Simple And Affordable Protocol To Assess Censer Seed Dispersal: First Confirmation Of The Mechanism In The Genus Solanum, Abigail J. Motter, Christopher T. Martine, Melody P. Sain

Faculty Journal Articles

The censer seed dispersal mechanism, whereby mature fruits are retained on plants and seeds dispersed by mechanical shaking, is among the most specialized wind-aided seed dispersal strategies employed by the flowering plants. An efficient, affordable, and easily repeatable protocol for determining whether a species uses this unusual mechanism of seed dispersal is lacking. Our focal species, Solanum tudununggae, is one of just two Solanum species (in a fleshy-fruited genus of ca. 1200 species) hypothesized to use this dispersal mechanism as a means to move seeds farther from parent plants than would gravity alone.

Kernel Density Estimate (Kde) Surfaces Of Wintering Tidal Marsh Birds Along The Mississippi Gulf Coast, Carlos Ramirez-Reyes, Kristine O. Evans, Mark S. Woodrey, Rachel V. Anderson, Jared Feura, Landon R. Jones, Raymond B. Iglay

Research Data

This dataset accompanies the article Spatial patterns of habitat use of wintering tidal marsh birds along the Mississippi Gulf Coast and includes kernel density estimate (KDE) raster layers describing spatial patterns of bird abundance and community richness derived from winter bird surveys. The study examined landscape features associated with the occurrence and spatial distribution of eight tidal marsh bird species during the non-breeding season along the Mississippi Gulf Coast.

Using field observations collected along fixed transects, the analysis evaluated differences between occupied and unoccupied transects, associations between bird occurrence and landscape-level predictors at ecologically relevant spatial scales, and species co-occurrence …

Combined Glycoprotein Mutations In Rabies Virus Promote Astrocyte Tropism And Protective Cns Immunity In Mice, Mirjam Anna Rita Bertoune, Corinna Kolbe, Ann-Cathrin Werner, Maren Steinmetz, Bernhard Dietzschold, Eberhard Weihe

Department of Microbiology and Immunology Faculty Papers

Rabies virus (RABV) causes fatal encephalitis once it invades the central nervous system (CNS), and treatment options are extremely limited at this stage. We investigated the recombinant RABV variants SPBN, SPBNGA (glycoprotein substitution R333E), SPBNGAK (R333E plus N194K), SPBNGAS (R333E plus N194S), and TriGAS (three copies of the R333E/N194S glycoprotein). We evaluated their cellular tropism and immune activation in an intracerebral mouse infection model using immunohistochemistry and confocal immunofluorescence. SPBNGAK (R333E/N194K) resulted in mixed neuronal and astrocytic infection and lethal disease. In contrast, the R333E/N194S mutations in the GAS variants were associated with reduced neuronal infection and apparent astrocyte-restricted infection …

Complete Genome Characterization Of A New Alphapartitivirus Identified In The Ectomycorrhizal Fungus Lactarius Mediterraneensis, Aigul Kali̇yeva, Ergi̇n Şahi̇n, Gülce Edi̇ş, Ilgaz Akata

Turkish Journal of Botany

Viruses that naturally infect fungi capable of forming mycorrhizal symbioses remain poorly studied. In the present study, a new partitivirus associated with the basidiomycete mycorrhizal fungus Lactarius mediterraneensis was identified and characterized, and it was designated as Lactarius mediterraneensis partitivirus 1 (LmPV1). The complete genome of LmPV1 was determined through high throughput sequencing of double-stranded RNA (dsRNA) extracts and confirmed by Sanger sequencing of RLM-RACE PCR amplicons. T he genome comprises two dsRNA segments, 1899 bp and 1957 bp, each containing a single open reading frame (ORF) a putative RNA-dependent RNA polymerase (RdRp) and a capsid protein (CP). Comparative analysis …

Nilotinib-Mediated Reprogramming Of Bone Marrow Macrophages Alters Hematopoietic Stem Cell Fate In Chronic Myeloid Leukemia, Tiffany Davia Ricketts

ETDs from 2020-2029

Tyrosine kinase inhibition (TKI) is highly effective and promotes favorable long-term outcomes for many patients with chronic myeloid leukemia (CML). However, many patients experience treatment resistance or recurrence after TKI cessation due to leukemic stem cell (LSC) persistence within the hematopoietic stem cell (HSC) niche. Within the niche, macrophages adopt different activation states to alter HSC function, however, CML disrupts niche signals to selectively support LSCs and macrophages may contribute to this process. We hypothesize that macrophages contribute to pro-inflammatory activation within the niche to promote LSC development and nilotinib will reprogram macrophages to selectively support non-leukemic stem cells. To …

Conserved Chromatin Programs Orchestrate Cardiac Cell States In Health And Disease And Drive Cardiomyocyte Proliferation After Injury, Xiaoxiao Geng

ETDs from 2020-2029

Chromatin structure is a central regulator of gene expression and cellular identity, yet the chromatin structural factors driving cardiac disease and regeneration remain incompletely defined. This dissertation investigates how modulation of chromatin architecture shapes pathological and regenerative cardiac phenotypes through integrated single-cell transcriptomic, epigenomic, and functional analyses. To determine whether chromatin structural regulators distinguish healthy from diseased cardiac states, we curated a comprehensive list of chromatin structural genes and applied it to single-nuclei RNA sequencing datasets from human hearts with and without dilated cardiomyopathy (DCM). Chromatin structural gene expression effectively stratified cardiomyocyte and fibroblast populations by disease status. Diseased cardiomyocytes …

Downregulation Of Slc40a1 Leads To Iron Accumulation In Fibrotic Lung Fibroblasts, Quanjin Dang, Chaoqun Huang, Yurong Liang, Akshaya Surendran, Dharanya Muthiah, Kishore Vaddadi, Sankha Hewawasam, Tingting W Mills, Lin Liu

Faculty, Staff and Student Publications

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbestos-induced lung fibrosis mice. Iron was partially co-localized with the …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

Community Synchrony In Aquatic Macroinvertebrates Is Unrelated To Environmental Variability But Differs Among Functional Feeding Groups, Anthony J. Pignatelli, Tad Dallas

Faculty Publications

Environments are becoming increasingly more variable, as a function of climate change. As this occurs, species may be exposed to conditions outside their preferred range. Such variability in the environment can influence community abundance as individual species respond either similarly (synchronous dynamics) or differently (asynchronous dynamics) to each other. These fluctuations in abundances are important for understanding the impact of environmental variability on species temporal fluctuations in aquatic macroinvertebrates. This group of organisms is species-rich and highly sensitive to environmental fluctuations. We analyzed 18 stream macroinvertebrate communities sampled by the National Ecological Observatory Network between 2014 and2022 to understand how …