Medical Specialties Commons^™

P2y2 Purinergic Receptor Gene Deletion Protects Mice From Bacterial Endotoxin And Sepsis-Associated Liver Injury And Mortality, Athis R Arunachalam, Sanju S Samuel, Arunmani Mani, Janielle P Maynard, Kelsey M Stayer, Eric Dybbro, Subapradha Narayanan, Aalekhya Biswas, Saliha Pathan, Krishnakant Soni, Abu Hena Mostafa Kamal, Chandra Shekar R Ambati, Nagireddy Putluri, Moreshwar S Desai, Sundararajah Thevananther

Faculty, Staff and Students Publications

The liver plays a significant role in regulating a wide range of metabolic, homeostatic, and host-defense functions. However, the impact of liver injury on the host's ability to control bacteremia and morbidity in sepsis is not well understood. Leukocyte recruitment and activation lead to cytokine and chemokine release, which, in turn, trigger hepatocellular injury and elevate nucleotide levels in the extracellular milieu. P2Y2 purinergic receptors, G protein-coupled and activated by extracellular ATP/UTP, are expressed at the cell surface of hepatocytes and nonparenchymal cells. We sought to determine whether P2Y2 purinergic receptor function is necessary for the maladaptive host response to …

Risk-Adjusted Cumulative Sum For Early Detection Of Hospitals With Excess Perioperative Mortality, Vivi W Chen, Alexis P Chidi, Yongquan Dong, Peter A Richardson, David A Axelrod, Laura A Petersen, Nader N Massarweh

Faculty, Staff and Students Publications

IMPORTANCE: National surgical quality improvement programs lack tools for early detection of quality or safety concerns, which risks patient safety because of delayed recognition of poor performance.

OBJECTIVE: To compare the risk-adjusted cumulative sum (CUSUM) with episodic evaluation for early detection of hospitals with excess perioperative mortality.

DESIGN, SETTING, AND PARTICIPANTS: National, observational, hospital-level, comparative effectiveness study of 697 566 patients. Identification of hospitals with excess, risk-adjusted, quarterly 30-day mortality using observed to expected ratios (ie, current criterion standard in the Veterans Affairs Surgical Quality Improvement Program) was compared with the risk-adjusted CUSUM. Patients included in the study underwent a …

Endoscopic Vacuum Therapy For Treatment Of Spontaneous And Iatrogenic Upper Gastrointestinal Defects, Kavea Panneerselvam, Jake S Jacob, Ronald E Samuel, Andy Tau, Gyanprakash A Ketwaroo, Wasif M Abidi, Robert J Sealock

Faculty, Staff and Students Publications

BACKGROUND/AIMS: Endoscopic vacuum therapy (EVT) can heal a variety of defects within the gastrointestinal (GI) tract via applying negative pressure, which reduces the defect size, aspirates the infected fluid, and promotes granulation tissue. Here we present our experience with EVT as it relates to both spontaneous and iatrogenic upper GI tract perforations, leaks, and fistulas.

METHODS: This retrospective study was conducted at four large hospital centers. All patients who underwent EVT between June 2018 and March 2021 were included. Data on multiple variables were collected, including demographics, defect size and location, number and intervals of EVT exchanges, technical success, and …

An Automated Respiratory Data Pipeline For Waveform Characteristic Analysis, Savannah Lusk, Christopher S Ward, Andersen Chang, Avery Twitchell-Heyne, Shaun Fattig, Genevera Allen, Joanna L Jankowsky, Russell S Ray

Faculty, Staff and Students Publications

Comprehensive and accurate analysis of respiratory and metabolic data is crucial to modelling congenital, pathogenic and degenerative diseases converging on autonomic control failure. A lack of tools for high-throughput analysis of respiratory datasets remains a major challenge. We present Breathe Easy, a novel open-source pipeline for processing raw recordings and associated metadata into operative outcomes, publication-worthy graphs and robust statistical analyses including QQ and residual plots for assumption queries and data transformations. This pipeline uses a facile graphical user interface for uploading data files, setting waveform feature thresholds and defining experimental variables. Breathe Easy was validated against manual selection by …

Advancements In Dendritic Cell Vaccination: Enhancing Efficacy And Optimizing Combinatorial Strategies For The Treatment Of Glioblastoma, Robert Subtirelu, Eric Teichner, Arjun Ashok, Chitra Parikh, Sahithi Talasila, Irina-Mihaela Matache, Ahab Alnemri, Victoria Anderson, Osmaan Shahid, Sricharvi Mannam, Andrew Lee, Thomas Werner, Mona-Elisabeth Revheim, Abass Alavi

Student Papers, Posters & Projects

Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of ¹⁸F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of …

Anthocyanins: Molecular Aspects On Their Neuroprotective Activity, César A Zaa, Álvaro J Marcelo, Zhiqiang An, José L Medina-Franco, Marco A Velasco-Velázquez

Faculty, Staff and Student Publications

Anthocyanins are a type of flavonoids that give plants and fruits their vibrant colors. They are known for their potent antioxidant properties and have been linked to various health benefits. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lower the risk of neurodegenerative diseases. Anthocyanins exhibit neuroprotective effects that could potentially alleviate symptoms associated with such diseases. In this review, we compiled and discussed a large body of evidence supporting the neuroprotective role of anthocyanins. Our examination encompasses human studies, animal models, …

The Influence Of Obesity On Outcomes With Immune Checkpoint Blockade: Clinical Evidence And Potential Biological Mechanisms, Andrew W Hahn, Neha Venkatesh, Pavlos Msaouel, Jennifer L Mcquade

Faculty, Staff and Student Publications

Immune checkpoint blockade (ICB) is a mainstay of treatment for advanced cancer, yet tumor response and host toxicity are heterogenous in those patients who receive ICB. There is growing interest in understanding how host factors interact with tumor intrinsic properties and the tumor microenvironment to influence the therapeutic index with ICB. Obesity, defined by body mass index, is a host factor associated with improved outcomes in select cancers when treated with ICB. While the biological mechanism for this obesity paradox is not fully understood, pre-clinical and translational studies suggest obesity may potentially impact tumor metabolism, inflammation, and angiogenesis. Herein, we …

Correction: Microrna 603 Acts As A Tumor Suppressor And Inhibits Triple-Negative Breast Cancer Tumorigenesis By Targeting Elongation Factor 2 Kinase, Recep Bayraktar, Martin Pichler, Pinar Kanlikilicer, Cristina Ivan, Emine Bayraktar, Nermin Kahraman, Burcu Aslan, Serpil Oguztuzun, Mustafa Ulasli, Ahmet Arslan, George Calin, Gabriel Lopez-Berestein, Bulent Ozpolat

Faculty, Staff and Student Publications

No abstract provided.

Daily Fosfomycin Versus Levofloxacin For Complicated Urinary Tract Infections, Nadine Rouphael, Patricia Winokur, Michael C Keefer, Jessica Traenkner, Ana Drobeniuc, Yohei Doi, Sonal Munsiff, Vance G Fowler, Scott Evans, Randolph E Oler, Bonifride Tuyishimire, Marina Lee, Varduhi Ghazaryan, Henry F Chambers

Faculty, Staff and Student Publications

Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.

The Uncharted Role Of Her2 Mutant Alleles In Breast Cancer, Rashi Kalra, Bora Lim, Matthew J Ellis, Shyam M Kavuri

Faculty, Staff and Student Publications

Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.

Sdc1 And Itga2 As Novel Prognostic Biomarkers For Pdac Related To Ipmn, Chuan-Long Zhang, Qian Shen, Fu-Dong Liu, Fan Yang, Meng-Qi Gao, Xiao-Chen Jiang, Yi Li, Xi-Yuan Zhang, Ge-Er En, Xue Pan, Bo Pang

Faculty, Staff and Student Publications

The existing biomarkers are insufficient for predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). Intraductal papillary mucinous neoplasm (IPMN) is a precursor to PDAC; therefore, identifying biomarkers from differentially expressed genes (DEGs) of PDAC and IPMN is a new and reliable strategy for predicting the prognosis of PDAC. In this study, four datasets were downloaded from the Gene Expression Omnibus database and standardized using the R package 'limma.' A total of 51 IPMN and 81 PDAC samples were analyzed, and 341 DEGs in PDAC and IPMN were identified; DEGs were involved in the extracellular matrix and tumor microenvironment. An acceptable …

A Small-Molecule Inhibitor Of Topbp1 Exerts Anti-Myc Activity And Synergy With Parp Inhibitors, Fang-Tsyr Lin, Kang Liu, Lidija A Wilhelms Garan, Helena Folly-Kossi, Yongcheng Song, Shwu-Jiuan Lin, Weei-Chin Lin

Faculty, Staff and Students Publications

We have previously identified TopBP1 (topoisomerase IIβ-binding protein 1) as a promising target for cancer therapy, given its role in the convergence of Rb, PI(3)K/Akt, and p53 pathways. Based on this, we conducted a large-scale molecular docking screening to identify a small-molecule inhibitor that specifically targets the BRCT7/8 domains of TopBP1, which we have named 5D4. Our studies show that 5D4 inhibits TopBP1 interactions with E2F1, mutant p53, and Cancerous Inhibitor of Protein Phosphatase 2A. This leads to the activation of E2F1-mediated apoptosis and the inhibition of mutant p53 gain of function. In addition, 5D4 disrupts the interaction of TopBP1 …

The Potential Weight Loss Benefits Of Tirzepatide: A Double-Edged Sword?, Muhammad Taha Nasim, Ayesha Ali, Muhammad Tabish Nasim

Medical College Documents

No abstract provided.

Sigma1 Regulates Lipid Droplet-Mediated Redox Homeostasis Required For Prostate Cancer Proliferation, Halley Oyer, Alexandra Steck, Charles Longen, Sanjana Venkat, Konuralp Bayrak, Eleanor Munger, Dan Fu, Paola Castagnino, Christina Sanders, Nathalia Tancler, My Mai, Justin Myers, Matthew Schiewer, Nan Chen, Elahe Mostaghel, Felix Kim

Department of Urology Faculty Papers

UNLABELLED: Lipid droplets (LD) are dynamic organelles that serve as hubs of cellular metabolic processes. Emerging evidence shows that LDs also play a critical role in maintaining redox homeostasis and can mitigate lipid oxidative stress. In multiple cancers, including prostate cancer, LD accumulation is associated with cancer aggressiveness, therapy resistance, and poor clinical outcome. Prostate cancer arises as an androgen receptor (AR)-driven disease. Among its myriad roles, AR mediates the biosynthesis of LDs, induces autophagy, and modulates cellular oxidative stress in a tightly regulated cycle that promotes cell proliferation. The factors regulating the interplay of these metabolic processes downstream of …

Mga-Seq: Robust Identification Of Extrachromosomal Dna And Genetic Variants Using Multiple Genetic Abnormality Sequencing, Da Lin, Yanyan Zou, Xinyu Li, Jinyue Wang, Qin Xiao, Xiaochen Gao, Fei Lin, Ningyuan Zhang, Ming Jiao, Yu Guo, Zhaowei Teng, Shiyi Li, Yongchang Wei, Fuling Zhou, Rong Yin, Siheng Zhang, Lingyu Xing, Weize Xu, Xiaofeng Wu, Bing Yang, Ke Xiao, Chengchao Wu, Yingfeng Tao, Xiaoqing Yang, Jing Zhang, Sheng Hu, Shuang Dong, Xiaoyu Li, Shengwei Ye, Zhidan Hong, Yihang Pan, Yuqin Yang, Haixiang Sun, Gang Cao

Children’s Nutrition Research Center Staff Publications

Genomic abnormalities are strongly associated with cancer and infertility. In this study, we develop a simple and efficient method - multiple genetic abnormality sequencing (MGA-Seq) - to simultaneously detect structural variation, copy number variation, single-nucleotide polymorphism, homogeneously staining regions, and extrachromosomal DNA (ecDNA) from a single tube. MGA-Seq directly sequences proximity-ligated genomic fragments, yielding a dataset with concurrent genome three-dimensional and whole-genome sequencing information, enabling approximate localization of genomic structural variations and facilitating breakpoint identification. Additionally, by utilizing MGA-Seq, we map focal amplification and oncogene coamplification, thus facilitating the exploration of ecDNA's transcriptional regulatory function.

Recent Advances In The Synthesis And Antioxidant Activity Of Low Molecular Mass Organoselenium Molecules, João M Anghinoni, Paloma T Birmann, Marcia J Da Rocha, Caroline S Gomes, Michael J Davies, César A Brüning, Lucielli Savegnago, Eder J Lenardão

Faculty, Staff and Student Publications

Selenium is an essential trace element in living organisms, and is present in selenoenzymes with antioxidant activity, like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). The search for small selenium-containing molecules that mimic selenoenzymes is a strong field of research in organic and medicinal chemistry. In this review, we review the synthesis and bioassays of new and known organoselenium compounds with antioxidant activity, covering the last five years. A detailed description of the synthetic procedures and the performed in vitro and in vivo bioassays is presented, highlighting the most active compounds in each series.

Association Of Dcis Size And Margin Status With Risk Of Developing Breast Cancer Post-Treatment: Multinational, Pooled Cohort Study, Renée S J M Schmitz, Alexandra W Van Den Belt-Dusebout, Karen Clements, Yi Ren, Chiara Cresta, Jasmine Timbres, Yat-Hee Liu, Danalyn Byng, Thomas Lynch, Brian A Menegaz, Deborah Collyar, Terry Hyslop, Samantha Thomas, Jason K Love, Michael Schaapveld, Proteeti Bhattacharjee, Marc D Ryser, Elinor Sawyer, E Shelley Hwang, Alastair Thompson, Jelle Wesseling, Esther H Lips, Marjanka K Schmidt

Faculty, Staff and Student Publications

OBJECTIVE: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer.

DESIGN: Multinational, pooled cohort study.

SETTING: Four large international cohorts.

PARTICIPANTS: Patient level data on 47 695 women with a diagnosis of pure, primary DCIS between 1999 and 2017 in the Netherlands, UK, and US who underwent surgery, either breast conserving or mastectomy, often followed by radiotherapy or endocrine treatment, or both.

MAIN OUTCOME MEASURES: The main outcomes were 10 year cumulative …

Enolase Inhibitors As Early Lead Therapeutics Against Trypanosoma Brucei, Colm P Roster, Danielle Lavigne, Jillian E Milanes, Emily Knight, Heidi D Anderson, Sabrina Pizarro, Elijah M Harding, Meredith T Morris, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian Dominy, Daniel C Whitehead, Md Nasir Uddin, Steven W Millward, James C Morris

Faculty, Staff and Student Publications

Glucose metabolism is critical for the African trypanosome, Trypanosoma brucei, serving as the lone source of ATP production for the bloodstream form (BSF) parasite in the glucose-rich environment of the host blood. Recently, phosphonate inhibitors of human enolase (ENO), the enzyme responsible for the interconversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) in glycolysis or PEP to 2-PG in gluconeogenesis, have been developed for the treatment of glioblastoma multiforme (GBM). Here, we have tested these agents against T. brucei ENO (TbENO) and found the compounds to be potent enzyme inhibitors and trypanocides. For example, (1-hydroxy-2-oxopyrrolidin-3-yl) phosphonic acid (deoxy-SF2312) …

The Lin28b/Wnt5a Axis Drives Pancreas Cancer Through Crosstalk Between Cancer Associated Fibroblasts And Tumor Epithelium, Zhaoqi Shu, Minghe Fan, Bo Tu, Zhiheng Tang, Haojie Wang, Haimeng Li, Hengchao Li, Meng Yuan, Jingru Bai, Sihan Huo, Lina Wang, Wei-Guo Zhu, Wei Wang, Xiaoyun Liu, Shaokun Shu, Ying Zhao

Faculty, Staff and Student Publications

Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9's production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in …

Simian Immunodeficiency Virus-Infected Rhesus Macaques With Aids Co-Develop Cardiovascular Pathology And Encephalitis, Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams

Nebraska Center for Virology: Faculty Publications

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/ macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently …

Neuroprotective Agents With Therapeutic Potential For Covid-19, César A Zaa, Clara Espitia, Karen L Reyes-Barrera, Zhiqiang An, Marco A Velasco-Velázquez

Faculty, Staff and Student Publications

COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate …

Optimization Of Pore Characteristics Of Graphite-Based Anode For Li-Ion Batteries By Control Of The Particle Size Distribution, Yun-Jeong Choi, Young-Seak Lee, Ji-Hong Kim, Ji-Sun Im

Faculty, Staff and Student Publications

We investigate the reassembly techniques for utilizing fine graphite particles, smaller than 5 µm, as high-efficiency, high-rate anode materials for lithium-ion batteries. Fine graphite particles of two sizes (0.4-1.2 µm and 5 µm) are utilized, and the mixing ratio of the two particles is varied to control the porosity of the assembled graphite. The packing characteristics of the assembled graphite change based on the mixing ratio of the two types of fine graphite particles, forming assembled graphite with varying porosities. The open porosity of the manufactured assembled graphite samples ranges from 0.94% to 3.55%, while the closed porosity ranges from …

Irf1 Regulates Self-Renewal And Stress Responsiveness To Support Hematopoietic Stem Cell Maintenance, Alexandra J S Rundberg Nilsson, Hongxu Xian, Shabnam Shalapour, Jörg Cammenga, Michael Karin

Faculty, Staff and Student Publications

Hematopoietic stem cells (HSCs) are tightly controlled to maintain a balance between blood cell production and self-renewal. While inflammation-related signaling is a critical regulator of HSC activity, the underlying mechanisms and the precise functions of specific factors under steady-state and stress conditions remain incompletely understood. We investigated the role of interferon regulatory factor 1 (IRF1), a transcription factor that is affected by multiple inflammatory stimuli, in HSC regulation. Our findings demonstrate that the loss of IRF1 from mouse HSCs significantly impairs self-renewal, increases stress-induced proliferation, and confers resistance to apoptosis. In addition, given the frequent abnormal expression of IRF1 in …

Tak1 And Tbk1 Are Differentially Required By Gmp- And Lmpp-Like Leukemia Stem Cells, Austin P. Runde, Joseph Michael Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Allan Youmaran, Mattias Lenz, Rohit Thalla, Wei Wei, Peter Breslin S.J., Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow. Aside from the M3 subtype (PML-RARA⁺), AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a 2-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine. Despite 60-70% of patients achieving complete remission (CR), at least half of CR-achieving patients …

Bayesian Parametric Models For Survival Prediction In Medical Applications, Iwan Paolucci, Yuan-Mao Lin, Jessica Albuquerque Marques Silva, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Background: Evidence-based treatment decisions in medicine are made founded on population-level evidence obtained during randomized clinical trials. In an era of personalized medicine, these decisions should be based on the predicted benefit of a treatment on a patient-level. Survival prediction models play a central role as they incorporate the time-to-event and censoring. In medical applications uncertainty is critical especially when treatments differ in their side effect profiles or costs. Additionally, models must be adapted to local populations without diminishing performance and often without the original training data available due to privacy concern. Both points are supported by Bayesian models-yet they …

Apple Crispr-Cas9-A Recipe For Successful Targeting Of Agamous-Like Genes In Domestic Apple, Seth Jacobson, Natalie Bondarchuk, Thy Anh Nguyen, Allison Canada, Logan Mccord, Timothy S Artlip, Philipp Welser, Amy L Klocko

Faculty, Staff and Student Publications

Fruit trees and other fruiting hardwood perennials are economically valuable, and there is interest in developing improved varieties. Both conventional breeding and biotechnology approaches are being utilized towards the goal of developing advanced cultivars. Increased knowledge of the effectiveness and efficiency of biotechnology approaches can help guide use of the CRISPR gene-editing technology. Here, we examined CRISPR-Cas9-directed genome editing in the valuable commodity fruit tree Malus x domestica (domestic apple). We transformed two cultivars with dual CRISPR-Cas9 constructs designed to target two AGAMOUS-like genes simultaneously. The main goal was to determine the effectiveness of this approach for achieving target …

Phenotypic Maps For Precision Medicine: A Promising Systems Biology Tool For Assessing Therapy Response And Resistance At A Personalized Level, Sayantan Bhattacharyya, Shafqat F Ehsan, Loukia G Karacosta

Faculty, Staff and Student Publications

In this perspective we discuss how tumor heterogeneity and therapy resistance necessitate a focus on more personalized approaches, prompting a shift toward precision medicine. At the heart of the shift towards personalized medicine, omics-driven systems biology becomes a driving force as it leverages high-throughput technologies and novel bioinformatics tools. These enable the creation of systems-based maps, providing a comprehensive view of individual tumor's functional plasticity. We highlight the innovative PHENOSTAMP program, which leverages high-dimensional data to construct a visually intuitive and user-friendly map. This map was created to encapsulate complex transitional states in cancer cells, such as Epithelial-Mesenchymal Transition (EMT) …

Decoding Meningioma Heterogeneity And Neoplastic Cell-Macrophage Interaction Through Single-Cell Transcriptome Profiling Across Pathological Grades, Hailang Fan, Lairong Song, Jian Fan, Junpeng Ma, Xiaojie Li, Junting Zhang, Jian Hu, Zhen Wu, Dake Zhang, Liang Wang

Faculty, Staff and Student Publications

Background: Analyzing meningioma of distinct pathological types at the single-cell level can provide new and valuable insights into the specific biological mechanisms of each cellular subpopulation, as well as their vital interplay within the tumor microenvironment.

Methods: We recruited patients diagnosed with four distinct types of meningioma and performed single-cell RNA sequencing on their tumor samples, concurrently analyzing a publicly available dataset for comparison. Next, we separated the cells into discrete clusters and identified their unique identities. Using pseudotime analysis, we demonstrated cellular differentiation and dynamics. To investigate biological function, we employed weighted gene co-expression network analysis, gene regulatory network, …

Identification Of Chronic Wasting Disease Prions In Decaying Tongue Tissues From Exhumed White-Tailed Deer, Paulina Soto, Francisca Bravo-Risi, Rebeca Benavente, Stuart Lichtenberg, Mitch Lockwood, J Hunter Reed, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) prions cause fatal neuropathies in farmed and free-ranging cervids. The deposition of prions in natural and humanmade environmental components has been implicated as a major mechanism mediating CWD spread in wild and captive populations. Prions can be deposited in the environment through excreta, tissues, and carcasses from pre-clinical and clinical animals. Furthermore, burial of CWD-positive animals may reduce but not completely mitigate prion spread from carcasses into the surrounding environment. Here, we analyzed exhumed, decaying deer carcasses for the presence of CWD prions. By analyzing tongue tissues through the protein misfolding cyclic amplification (PMCA) technique, we …

Uracil-Dna Glycosylase Of Murine Gammaherpesvirus 68 Binds Cognate Viral Replication Factors Independently Of Its Catalytic Residues, Kyle R Smith, Somnath Paul, Qiwen Dong, Orchi Anannya, Darby G Oldenburg, J Craig Forrest, Kevin M Mcbride, Laurie T Krug

Faculty, Staff and Student Publications

Herpesviruses are large double-stranded DNA viruses that encode core replication proteins and accessory factors involved in nucleotide metabolism and DNA repair. Mammalian uracil-DNA glycosylases (UNG) excise deleterious uracil residues from their genomic DNA. Each herpesvirus UNG studied to date has demonstrated conservation of the enzymatic function to excise uracil residues from DNA. We previously reported that a murine gammaherpesvirus (MHV68) with a stop codon in ORF46 (ORF46.stop) that encodes for vUNG was defective in lytic replication and latency in vivo. However, a mutant virus that expressed a catalytically inactive vUNG (ORF46.CM) had no replication defect unless coupled with additional …