Digital Commons Network^™

A Case For Accelerating Standards To Achieve The Fair Principles Of Environmental Health Research Experimental Data, Rance Nault, Matthew C. Cave, Gabriele Ludewig, Hunter N. B. Moseley, Kelly G. Pennell, Tim Zacharewski

Markey Cancer Center Faculty Publications

BACKGROUND: Funding agencies, publishers, and other stakeholders are pushing environmental health science investigators to improve data sharing; to promote the findable, accessible, interoperable, and reusable (FAIR) principles; and to increase the rigor and reproducibility of the data collected. Accomplishing these goals will require significant cultural shifts surrounding data management and strategies to develop robust and reliable resources that bridge the technical challenges and gaps in expertise.

OBJECTIVE : In this commentary, we examine the current state of managing data and metadata—referred to collectively as (meta)data—in the experimental environmental health sciences. We introduce new tools and resources based on in vivo …

A Proposed Fair Approach For Disseminating Geospatial Information System Maps, P. Travis Thompson, Sweta Ojha, Christian D. Powell, Kelly G. Pennell, Hunter N. B. Moseley

Markey Cancer Center Faculty Publications

We present a draft Minimum Information about Geospatial Information System (MIaGIS) standard for facilitating public deposition of geospatial information system (GIS) datasets that follows the FaIR (Findable, accessible, Interoperable and Reusable) principles. the draft MIaGIS standard includes a deposition directory structure and a minimum javascript object notation (JSON) metadata formatted file that is designed to capture critical metadata describing GIS layers and maps as well as their sources of data and methods of generation. the associated miagis Python package facilitates the creation of this MIAGIS metadata file and directly supports metadata extraction from both Esri JSON and GEOJSON GIS data …

Creation Of Egd-Derived Gastric Cancer Organoids To Predict Treatment Responses, Hannah Mcdonald, Megan Harper, Kristen S. Hill, Anqi Gao, Angelica L. Solomon, Charles J. Bailey, Miranda Lin, Mautin Barry-Hundeyin, Michael Cavnar, Samuel H. Mardini, Prakash Pandalai, Reema A. Patel, Jill M. Kolesar, Justin A. Rueckert, Lawrence Hookey, Mark Ropeleski, Shaila J. Merchant, Joseph Kim, Mei Gao

Markey Cancer Center Faculty Publications

Gastric adenocarcinoma (GAd) is the third leading cause of cancer-related deaths worldwide. Most patients require perioperative chemotherapy, yet methods to accurately predict responses to therapy are lacking. Thus, patients may be unnecessarily exposed to considerable toxicities. Here, we present a novel methodology using patient-derived organoids (PDOs) that rapidly and accurately predicts the chemotherapy efficacy for GAd patients.

Methods: Endoscopic GAd biopsies were obtained from 19 patients, shipped overnight, and PDOs were developed within 24 h. Drug sensitivity testing was performed on PDO single-cells with current standard-of-care systemic GAd regimens and cell viability was measured. Whole exome sequencing was used to …

Differential Inhibition Of Anaplerotic Pyruvate Carboxylation And Glutaminolysis-Fueled Anabolism Underlies Distinct Toxicity Of Selenium Agents In Human Lung Cancer, Teresa W-M Fan, Jason Winnike, Ahmad Al-Attar, Alex C. Belshoff, Pawel Lorkiewicz, Jin Lian Tan, Min Wu, Richard M. Higashi, Andrew N. Lane

Markey Cancer Center Faculty Publications

Past chemopreventive human trials on dietary selenium supplements produced controversial outcomes. They largely employed selenomethionine (SeM)-based diets. SeM was less toxic than selenite or methylseleninic acid (MSeA) to lung cancer cells. We thus investigated the toxic action of these Se agents in two non-small cell lung cancer (NSCLC) cell lines and ex vivo organotypic cultures (OTC) of NSCLC patient lung tissues. Stable isotope-resolved metabolomics (SIRM) using 13C6-glucose and 13C5,15N2-glutamine tracers with gene knockdowns were employed to examine metabolic dysregulations associated with cell type- and treatment-dependent phenotypic changes. Inhibition of key anaplerotic processes, pyruvate carboxylation (PyC) and glutaminolysis were elicited by …

Green Solvent Mediated Extraction Of Micro- And Nano-Plastic Particles From Water, Jameson R. Hunter, Qi Qiao, Yuxuan Zhang, Qing Shao, Czarena L. Crofcheck, Jian Shi

Markey Cancer Center Faculty Publications

The production of plastic and the amount of waste plastic that enters the ecosystem increases every year. Synthetic plastics gradually break down into particles on the micro‑ and nano‑scale in the environment. The micro‑ and nano‑plastics pose a significant ecological threat by transporting toxic chemicals and causing inflammation and cellular damage when ingested; however, removal of those particles from water is challenging using conventional separation methods. Deep eutectic solvents (DES), a new class of solvents composed of hydrogen bond donors and acceptors, have been proposed as a cheaper alternative to ionic liquids. Hydrophobic DES derived from natural compounds (NADES) show …

Identifying And Sharing Per-And Polyfluoroalkyl Substances Hot-Spot Areas And Exposures In Drinking Water, Sweta Ojha, P. Travis Thompson, Christian D. Powell, Hunter N. B. Moseley, Kelly G. Pennell

Markey Cancer Center Faculty Publications

Exposure to per- and polyfluoroalkyl substances (PFAS) in drinking water is widely recognized as a public health concern. Decision-makers who are responsible for managing PFAS drinking water risks lack the tools to acquire the information they need. In response to this need, we provide a detailed description of a Kentucky dataset that allows decision-makers to visualize potential hot-spot areas and evaluate drinking water systems that may be susceptible to PFAS contamination. The dataset includes information extracted from publicly available sources to create five different maps in ArcGIS Online and highlights potential sources of PFAS contamination in the environment in relation …

Noncovalent Interactions That Tune The Reactivities Of The Flavins In Bifurcating Electron Transferring Flavoprotein, María González-Viegas, Rajiv K. Kar, Anne-Frances Miller, Maria-Andrea Mroginski

Markey Cancer Center Faculty Publications

Bifurcating electron transferring flavoproteins (Bf-ETFs) tune chemically identical flavins to two contrasting roles. To understand how, we used hybrid quantum mechanical molecular mechanical calculations to characterize noncovalent interactions applied to each flavin by the protein. Our computations replicated the differences between the reactivities of the flavins: the electron transferring flavin ( ETflavin) was calculated to stabilize anionic semiquinone (ASQ) as needed to execute its single-electron transfers, whereas the Bf flavin (Bfflavin) was found to disfavor the ASQ state more than does free flavin and to be less susceptible to reduction. The stability of ETflavin ASQ was attributed in part to …

Novel Isolation Method Reveals Sex-Specific Composition And Neurotoxicity Of Small Extracellular Vesicles In A Mouse Model Of Alzheimer’S Disease, Ahmed Elsherbini, Zhihui Zhu, Zainuddin Quadri, Simone M. Crivelli, Xiaojia Ren, Hemendra J. Vekaria, Priyanka Tripathi, Liping Zhang, Wenbo Zhi, Erhard Bieberich

Markey Cancer Center Faculty Publications

We developed a new method to isolate small extracellular vesicles (sEVs) from male and female wild-type and 5xFAD mouse brains to investigate the sex-specific functions of sEVs in Alzheimer’s disease (AD). A mass spectrometric analysis revealed that sEVs contained proteins critical for EV formation and Aβ. ExoView analysis showed that female mice contained more GFAP and Aβ-labeled sEVs, suggesting that a larger proportion of sEVs from the female brain is derived from astrocytes and/or more likely to bind to Aβ. Moreover, sEVs from female brains had more acid sphingomyelinase (ASM) and ceramide, an enzyme and its sphingolipid product important for …

The Kappa Opioid Receptor Agonist 16-Bromo Salvinorin A Has Anti-Cocaine Effects Without Significant Effects On Locomotion, Food Reward, Learning And Memory, Or Anxiety And Depressive-Like Behaviors, Ross Van De Wetering, Amy Ewald, Susan Welsh, Lindsay Kornberger, Samuel E. Williamson, Bryan D. Mcelroy, Eduardo R. Butelman, Thomas E. Prisinzano, Bronwyn M. Kivell

Markey Cancer Center Faculty Publications

Kappa opioid receptor (KOR) agonists have preclinical antipsychostimulant effects; however, adverse side effects have limited their therapeutic development. In this preclinical study, conducted in Sprague Dawley rats, B6-SJL mice, and non-human primates (NHPs), we evaluated the G-protein-biased analogue of salvinorin A (SalA), 16-bromo salvinorin A (16-BrSalA), for its anticocaine effects, side effects, and activation of cellular signaling pathways. 16-BrSalA dose-dependently decreased the cocaine-primed reinstatement of drug-seeking behavior in a KOR-dependent manner. It also decreased cocaine-induced hyperactivity, but had no effect on responding for cocaine on a progressive ratio schedule. Compared to SalA, 16-BrSalA had an improved side effect profile, with …

Ariation In Tannin Content And Morphological Traits In Lotus Corniculatus L. (Bird’S-Foot Trefoil), A. H. Marshall, F. Ribaimont, R. P. Collins, D. Bryant, M. T. Abberton

IGC Proceedings (1977-2023)

Lotus corniculatus L. (bird's-foot trefoil) is a potentially valuable species for UK grassland agriculture. The herbage contains proanthocyanidins, or condensed tannins (CT's), which help to reduce bloat, have anthelmintic properties, can protect protein in the rumen, and thus potentially reduce N losses to the environment. It is currently a relatively minor species within UK grassland, as available varieties lack persistence in mixed swards (Hopkins et al., 1996). The seed used is of foreign bred varieties with no varieties bred specifically for the UK environment. To explore the feasibility of breeding L. corniculatus for the UK, variation in morphological traits, …

Ruminal Disappearance And Passage Rates In Fresh Nezasa Dwarf Bamboo Growing In Japanese Native Pasture, Masato Yayota, J. Karashima, T. Kokestu, M. Nakano, Shigeru Ohtani

IGC Proceedings (1977-2023)

Nezasa dwarf bamboo (Pleioblastus chino makino) is one of major native forages for grazing in Japan. However its nutritional utilisation in the rumen has been little studied. The object of this research was to measure ruminal disappearance and passage rates in fresh Nezasa dwarf bamboo compared with improved grass.

Perennial Ryegrass Variety Differences In Nutritive Value Characteristics, T. J. Gilliland, R. E. Agnew, A. M. Fearon, F. E. A. Wilson

IGC Proceedings (1977-2023)

Animal grazing performance at grass is predominately determined by herbage intake rates, with high yielding dairy cows requiring up to 20 kg/d DM within a limited grazing time (Gibb, 1998). Grass nutritional factors such as seasonal patterns in digestibility and water-soluble carbohydrate levels have been linked to animal productivity (Davies et al., 1991), while sward surface height, herbage mass, bulk density and green leaf mass have been shown to promote high grazing intake (Barrett et al., 2001). Furthermore, fatty acid profiles have been shown to improve the unsaturated fatty acid composition of milk, with potential human health benefits …

Devices And Methods For Removing Perflourinated Compounds From Contaminted Water, Dibakar Bhattacharyya Phd, Anthony Saad Phd, Rollie Mills Phd, L. E. Ormsbee Phd, M Abdul Mottaleb Phd

Civil Engineering Faculty Patents

PFAS compounds have emerged as a persistent and harmful environmental pollutant that present significant challenges to health and remediation. This patent describes a new technology that employs membrane technology along with thermo-responsive adsorption-desorption processes to remove perfluorinated compounds from contaminate water.

Validation Of Monitoring Septic Thymus Involution In Mice Using Ultrasound., Jianyao Xue, Xiang-An Li

Journal of Pharmacology & Nutritional Sciences

Sepsis is a dangerous condition commonly seen in the intensive care unit (ICU) of hospitals. It causes the thymus, a crucial immune organ, to shrink. This process is known as thymus involution. Although thymus involution is a natural process that occurs as we age, it is accelerated during sepsis. This process is associated with poor outcomes in septic patients, yet it had never been studied using ultrasonography in a septic mouse model. Researchers from the University of Kentucky have validated a non-invasive ultrasound imaging approach to monitor septic thymus involution in a cecum ligation and puncture (CLP) sepsis mouse model. …

The Last Of Us In Therapy: How Mind-Controlling Fungi And Gut Bacteria Affect Your Mental Health, Anastasia Lyon

Journal of Pharmacology & Nutritional Sciences

The "psilocybiome" represents the mutually beneficial relationship between ourselves, our bacteria, and psychedelic drugs. This short review briefly discusses the benefits and limitations surrounding the potential for psychedelic therapy to synergize with gut bacteria to help regulate and maintain proper balance in the immune system, diet, and stress levels. Psychedelic therapy is a novel treatment strategy that has the potential to improve patient mental health, and, by identifying the types of gut bacteria present in patients, it can aid in personalizing medicine by determining how well their "psilocybiome" may respond.

(Pro)Renin Receptor And Its Soluble Form In Metabolic Dysfunction: Friend Or Foe?, Gertrude Arthur

Journal of Pharmacology & Nutritional Sciences

(Pro)renin receptor is component of the renin angiotensin system which has been shown to be involved in several physiological and pathophysiological processes including blood pressure regulation and hypertension, water and electrolyte balance, kidney injury, obesity, and metabolic dysfunction. Enzymatic cleavage of prorenin receptor produces soluble prorenin receptor which can also activate the renin angiotensin system stimulate similar pathophysiological process like its full form receptor. This review explores findings on the role of prorenin receptor and soluble prorenin receptor in metabolic dysfunction and discusses the conflicting findings on soluble prorenin receptor in metabolic dysfunction.

Fiscal Year 2021 Fhwa-536 Report For The Kentucky Transportation Cabinet, Doug Kreis, Candice Wallace, Bryan Gibson, Sarah Mccormack

Kentucky Transportation Center Research Report

No abstract provided.

Flood Fatalities In Eastern Kentucky And The Public Health Legacy Of Mountaintop Removal Coal Mining, W. Jay Christian, Beverly May, Jeffery E. Levy

UK CARES Faculty Publications

Heavy rains at night caused severe flooding in eastern Kentucky on 28 July 2022, resulting in 39 deaths. Using publicly available information, we assembled a database of these fatalities, including demographic characteristics and location of death. We perturbed fatality locations and plotted them on a topographical map highlighting mountaintop removal mining with valley fill sites, where mountaintops were excavated to mine thin seams of coal. This map reveals many flood fatalities occurred along rivers or streams near such sites. Previous research suggests that surface mining has contributed to the majority of land cover change in this region, and this has …

Accelerating Colorectal Cancer Screening And Follow-Up Through Implementation Science (Accsis) In Appalachia: Protocol For A Group Randomized, Delayed Intervention Trial, Electra D. Paskett, Aaron J. Kruse-Diehr, Jill M. Oliveri, Robin C. Vanderpool, Darrell M. Gray Ii, Michael L. Pennell, Bin Huang, Gregory S. Young, Darla Fickle, Mark Cromo, Mira L. Katz, Paul L. Reiter, Melinda Rogers, David A. Gross, Vickie Fairchild, Wendy Xu, Angela Carman, Jean M. Walunis, Ann Scheck Mcalearney, Timothy R. Huerta, Saurabh Rahurkar, Erika Biederman, Mark B. Dignan

UK CARES Faculty Publications

Appalachian regions of Kentucky and Ohio are hotspots for colorectal cancer (CRC) mortality in the USA. Screening reduces CRC incidence and mortality; however, screening uptake is needed, especially in these underserved geographic areas. Implementation science offers strategies to address this challenge. The aim of the current study was to conduct multi-site, transdisciplinary research to evaluate and improve CRC screening processes using implementation science strategies. The study consists of two phases (Planning and Implementation). In the Planning Phase, a multilevel assessment of 12 health centers (HC) (one HC from each of the 12 Appalachian counties) was conducted by interviewing key informants, …

Combination Therapy With Trastuzumab And Niraparib: Quantifying Early Proliferative Alterations In Her2+ Breast Cancer Models, Ameer Mansur, Patrick N. Song, Yun Lu, Andrew C. Burns, Luke Sligh, Eddy S. Yang, Anna G. Sorace

Markey Cancer Center Faculty Publications

HER2–targeted treatments have improved survival rates in HER2+ breast cancer patients, yet poor responsiveness remains a major clinical obstacle. Recently, HER2+ breast cancer cells, both resistant and responsive to HER2–targeted therapies, have demonstrated sensitivity to poly–(ADP– ribose) polymerase (PARP) inhibition, independent of DNA repair deficiencies. This study seeks to describe biological factors that precede cell viability changes in response to the combination of trastuzumab and PARP inhibition. Treatment response was evaluated in HER2+ and HER2– breast cancer cells. Further, we evaluated the utility of 3′–Deoxy–3′–[18F]–fluorothymidine positron emission tomography ([18F]FLT–PET) imaging for early response assessment in a HER2+ patient derived xenograft …

Predictive Modeling Of Cave Entrance Locations: Relationships Between Surface And Subsurface Morphology, William Blitch, Adia R. Sovie, Benjamin Tobin

Faculty, Staff, and Affiliated Publications--KGS

Cave entrances directly connect the surface and subsurface geomorphology in karst landscapes. Understanding the spatial distribution of these features can help identify areas on the landscape that are critical to flow in the karst groundwater system. Sinkholes and springs are major locations of inflow and outflow from the groundwater system, respectively, however not all sinkholes and springs are equally connected to the main conduit system.

Predicting where on the landscape zones of high connectivity exist is a challenge because cave entrances are difficult to detect and imperfectly documented. Wildlife research has a similar issue of understanding the complexities of where …

Serum Amyloid A Augments The Atherogenic Effects Of Cholesteryl Ester Transfer Protein, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Preetha Shridas

Saha Cardiovascular Research Center Faculty Publications

Serum amyloid A (SAA) is predictive of CVD in humans and causes atherosclerosis in mice. SAA has many proatherogenic effects in vitro. However, HDL, the major carrier of SAA in the circulation, masks these effects. The remodeling of HDL by cholesteryl ester transfer protein (CETP) liberates SAA restoring its proinflammatory activity. Here, we investigated whether deficiency of SAA suppresses the previously described proatherogenic effect of CETP. ApoE¡/¡ mice and apoE¡/¡ mice deficient in the three acute-phase isoforms of SAA (SAA1.1, SAA2.1, and SAA3; “apoE¡/¡ SAA-TKO”) with and without adeno-associated virus-mediated expression of CETP were studied. There was no effect of …

Spatial Metabolomics Reveals Glycogen As An Actionable Target For Pulmonary Fibrosis, Lindsey R. Conroy, Harrison A. Clarke, Derek B. Allison, Samuel Santos Valenca, Qi Sun, Tara R. Hawkinson, Lyndsay E. A. Young, Juanita E. Ferreira, Autumn V. Hammonds, Jaclyn B. Dunne, Robert J. Mcdonald, Kimberly J. Absher, Brittany Dong, Ronald C. Bruntz, Kia H. Markussen, Jelena A. Juras, Warren J. Alilain, Jinze Liu, Matthew S. Gentry, Peggi M. Angel, Christopher M. Waters, Ramon C. Sun

Saha Cardiovascular Research Center Faculty Publications

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high- dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed …

Artificial Intelligence In Continuous Kidney Replacement Therapy, Lucas J. Liu, Tomonori Takeuchi, Jin Chen, Javier A. Neyra

Markey Cancer Center Faculty Publications

Over the past decade, artificial intelligence (AI) through machine learning (ML) has been increasingly used in health care applications. The use of AI/ML to enhance the provision of continuous kidney replacement therapy (CKRT) is an area of active investigation because of the growing clinical needs of critically ill patients and the abundance of multimodal data from the electronic health records (EHRs) and the CKRT machine itself. Importantly, best clinical practices of CKRT have not been sufficiently standardized, so there is considerable heterogeneity in utilization and deliverables. In this context, AI/ML-based tools could facilitate informed decisions to enhance CKRT goal-oriented deliver- …

Development And Characterization Of Nanobodies That Specifically Target The Oncogenic Phosphatase Of Regenerating Liver-3 (Prl-3) And Impact Its Interaction With A Known Binding Partner, Cnnm3, Caroline N. Smith, Kyle Kihn, Zachary A. Williamson, K. Martin Chow, Louis B. Hersh, Konstantin V. Korotkov, Daniel Deredge, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis. The mechanisms that drive PRL-3’s oncogenic functions are not well under- stood, partly due to a lack of research tools available to study this protein. We have begun to address these issues by developing alpaca-derived single domain antibodies, or nanobo- dies, targeting PRL-3 with a KD of 30–300 nM and no activity towards highly homologous family members PRL-1 and PRL-2. We found that longer and charged N-terminal tags on PRL-3, such as GFP and FLAG, changed PRL-3 localization compared to untagged protein, indicating that the nanobodies may provide …

Icam-1-Supar-Cd11b Axis Is A Novel Therapeutic Target For Metastatic Triple-Negative Breast Cancer, Dong Li, Hami Hemati, Younhee Park, Rokana Taftaf, Youbin Zhang, Jinpeng Liu, Massimo Cristofanilli, Xia Liu

Markey Cancer Center Faculty Publications

Accumulating evidence demonstrates that circulating tumor cell (CTC) clusters have higher metastatic ability than single CTCs and negatively correlate with cancer patient outcomes. Along with homotypic CTC clusters, heterotypic CTC clusters (such as neutrophil–CTC clusters), which have been identified in both cancer mouse models and cancer patients, lead to more efficient metastasis formation and worse patient outcomes. However, the mechanism by which neutrophils bind to CTCs remains elusive. In this study, we found that intercellular adhesion molecule-1 (ICAM-1) on triple- negative breast cancer (TNBC) cells and CD11b on neutrophils mediate tumor cell–neutrophil binding. Consequently, CD11b deficiency inhibited tumor cell–neutrophil binding …

Life Stressors And Immune Aging: Protective Effects Of Cognitive Reappraisal, Rebecca G. Reed, Steven R. Presnell, Ahmad Al-Attar, Charles T. Lutz, Suzanne C. Segerstrom

Markey Cancer Center Faculty Publications

Stressful life events may accelerate aspects of immune aging, but habitual use of an adaptive emotion regulation strategy, cognitive reappraisal, may attenuate these effects. This study examined whether cognitive reappraisal moderates the associations between life stressor frequency and stressor desirability on aspects of immune aging, including late-differentiated CD8+ T and natural killer (NK) cells and inflammatory markers (IL-6, TNF-α, and CRP), both between and within people in a longitudinal sample of 149 older adults (mean age = 77.8, range: 64–92 years). Participants reported stressful life events, use of cognitive reappraisal, and provided blood semiannually for up to 5 years to …

Single Fraction And Hypofractionated Radiation Cause Cochlear Damage, Hearing Loss, And Reduced Viability Of Merlin-Deficient Schwann Cells, Christine T. Dinh, Si Chen, Aida Nourbakhsh, Kyle Padgett, Perry Johnson, Stefania Goncalves, Olena Bracho, Esperanza Bas, Jorge Bohorquez, Paula V. Monje, Cristina Fernandez-Valle, Nagy Elsayyad, Xuezhong Liu, Scott M. Welford, Fred Telischi

Markey Cancer Center Faculty Publications

Background: Vestibular schwannomas (VS) are benign intracranial tumors caused by loss of function of the merlin tumor suppressor. We tested three hypotheses related to radiation, hearing loss (HL), and VS cell survival: (1) radiation causes HL by injuring auditory hair cells (AHC), (2) fractionation reduces radiation-induced HL, and (3) single fraction and equivalent appropriately dosed multi-fractions are equally effective at controlling VS growth. We investigated the effects of single fraction and hypofractionated radiation on hearing thresholds in rats, cell death pathways in rat cochleae, and viability of human merlin-deficient Schwann cells (MD-SC). Methods: Adult rats received cochlear irradiation with single …

The Plod2/Succinate Axis Regulates The Epithelial–Mesenchymal Plasticity And Cancer Cell Stemness, Yuxin Tong, Yifei Qi, Gaofeng Xiong, Junyan Li, Timothy L. Scott, Jie Chen, Daheng He, Linzhang Li, Chi Wang, Andrew N. Lane, Ren Xu

Markey Cancer Center Faculty Publications

Aberrant accumulation of succinate has been detected in many cancers. However, the cellular function and regulation of succinate in cancer progression is not completely understood. Using stable isotope-resolved metabolomics analysis, we showed that the epithelial mesenchymal transition (EMT) was associated with profound changes in metabolites, including elevation of cytoplasmic succinate levels. The treatment with cell-permeable succinate induced mesenchymal phenotypes in mammary epithelial cells and enhanced cancer cell stemness. Chromatin immunoprecipitation and sequence analysis showed that elevated cytoplasmic succinate levels were sufficient to reduce global 5-hydroxymethylcytosinene (5hmC) accumulation and induce transcriptional repression of EMT-related genes. We showed that expression of procollagen-lysine,2-oxoglutarate …

Reviewer Acknowledgments, Randy Wykoff Md, Mph & Tm, Rachel E. Dixon Mphil

Journal of Appalachian Health

As we reach our fifth year, we are particularly thankful for the contributions of our peer reviewers. The knowledge, expertise, and guidance offered by the people listed below have ensured that we can continue to share timely research to effect health and well-being across Appalachia.