Medical Specialties Commons^™

Hif1a-Dependent Induction Of Alveolar Epithelial Pfkfb3 Dampens Acute Lung Injury, Christine U Vohwinkel, Nana Burns, Ethan Coit, Xiaoyi Yuan, Eszter K Vladar, Christina Sul, Eric P Schmidt, Peter Carmeliet, Kurt Stenmark, Eva S Nozik, Rubin M Tuder, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during …

Aptamer Proteomics Of Serum Exosomes From Patients With Primary Raynaud's And Patients With Raynaud's At Risk Of Evolving Into Systemic Sclerosis, Sonsoles Piera-Velazquez, Simon T. Dillon, Xuesong Gu, Towia A. Libermann, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: A major unmet need for Systemic Sclerosis (SSc) clinical management is the lack of biomarkers for the early diagnosis of patients with Raynaud's Phenomenon at high risk of evolving into SSc.

OBJECTIVE: To identify proteins contained within serum exosomes employing an aptamer proteomic analysis that may serve to reveal patients with Raynaud's Phenomenon at risk of developing SSc.

METHODS: Exosomes were isolated from serum samples from patients with Primary Raynaud's Phenomenon and from patients with Raynaud's Phenomenon harbouring serum antinuclear antibodies (ANA) who may be at high risk of evolving into SSc. The expression of 1,305 proteins was quantified …

Human Health During Space Travel: State-Of-The-Art Review, Chayakrit Krittanawong, Nitin Kumar Singh, Richard A Scheuring, Emmanuel Urquieta, Eric M Bershad, Timothy R Macaulay, Scott Kaplin, Carly Dunn, Stephen F Kry, Thais Russomano, Marc Shepanek, Raymond P Stowe, Andrew W Kirkpatrick, Timothy J Broderick, Jean D Sibonga, Andrew G Lee, Brian E Crucian

Faculty, Staff and Student Publications

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, …

Engineering Naturally Occurring Cd7- T Cells For The Immunotherapy Of Hematological Malignancies, Abdullah Freiwan, Jaquelyn T Zoine, Jeremy Chase Crawford, Abishek Vaidya, Stefan A Schattgen, Jacquelyn A Myers, Sagar L Patil, Mahsa Khanlari, Hiroto Inaba, Jeffery M Klco, Charles G Mullighan, Giedre Krenciute, Peter J Chockley, Swati Naik, Deanna M Langfitt, Maksim Mamonkin, Esther A Obeng, Paul G Thomas, Stephen Gottschalk, M Paulina Velasquez

Faculty, Staff and Students Publications

Chimeric antigen receptor (CAR) T-cell therapy targeting T-cell acute lymphoblastic leukemia (T-ALL) faces limitations such as antigen selection and limited T-cell persistence. CD7 is an attractive antigen for targeting T-ALL, but overlapping expression on healthy T cells leads to fratricide of CD7-CAR T cells, requiring additional genetic modification. We took advantage of naturally occurring CD7- T cells to generate CD7-CAR (CD7-CARCD7-) T cells. CD7-CARCD7- T cells exhibited a predominantly CD4+ memory phenotype and had significant antitumor activity upon chronic antigen exposure in vitro and in xenograft mouse models. Based on these encouraging results, we next explored the utility of CD7- …

Period 2 Regulates Low-Dose Radioprotection Via Per2/Pgsk3Β/Β-Catenin/Per2 Loop, Aris T Alexandrou, Yixin Duan, Shanxiu Xu, Clifford Tepper, Ming Fan, Jason Tang, Jonathan Berg, Wassim Basheer, Tyler Valicenti, Paul F Wilson, Matthew A Coleman, Andrew T Vaughan, Loning Fu, David J Grdina, Jefferey Murley, Aijun Wang, Gayle Woloschak, Jian Jian Li

Faculty, Staff and Students Publications

During evolution, humans are acclimatized to the stresses of natural radiation and circadian rhythmicity. Radiosensitivity of mammalian cells varies in the circadian period and adaptive radioprotection can be induced by pre-exposure to low-level radiation (LDR). It is unclear, however, if clock proteins participate in signaling LDR radioprotection. Herein, we demonstrate that radiosensitivity is increased in mice with the deficient Period 2 gene (Per2def) due to impaired DNA repair and mitochondrial function in progenitor bone marrow hematopoietic stem cells and monocytes. Per2 induction and radioprotection are also identified in LDR-treated Per2wt mouse cells and in human skin (HK18) and breast (MCF-10A) …

Rare Diseases And Space Health: Optimizing Synergies From Scientific Questions To Care, Maria Puscas, Gabrielle Martineau, Gurjot Bhella, Penelope E Bonnen, Phil Carr, Robyn Lim, John Mitchell, Matthew Osmond, Emmanuel Urquieta, Jaime Flamenbaum, Giuseppe Iaria, Yann Joly, Étienne Richer, Joan Saary, David Saint-Jacques, Nicole Buckley, Etienne Low-Decarie

Faculty, Staff and Students Publications

Knowledge transfer among research disciplines can lead to substantial research progress. At first glance, astronaut health and rare diseases may be seen as having little common ground for such an exchange. However, deleterious health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases. Here, we compare and contrast research and healthcare in the contexts of rare diseases and space health and identify common barriers and avenues of improvement. The prevalent genetic basis of most rare disorders contrasts sharply with the occupational considerations required to sustain human health in space. Nevertheless small sample …

Stabilized Core Gene And Pathway Election Uncovers Pan-Cancer Shared Pathways And A Cancer-Specific Driver, Pathum Kossinna, Weijia Cai, Xuewen Lu, Carrie S Shemanko, Qingrun Zhang

Department of Cancer Biology Faculty Papers

Approaches systematically characterizing interactions via transcriptomic data usually follow two systems: (i) coexpression network analyses focusing on correlations between genes and (ii) linear regressions (usually regularized) to select multiple genes jointly. Both suffer from the problem of stability: A slight change of parameterization or dataset could lead to marked alterations of outcomes. Here, we propose Stabilized COre gene and Pathway Election (SCOPE), a tool integrating bootstrapped least absolute shrinkage and selection operator and coexpression analysis, leading to robust outcomes insensitive to variations in data. By applying SCOPE to six cancer expression datasets (BRCA, COAD, KIRC, LUAD, PRAD, and THCA) in …

Activation Of Basal Forebrain-To-Lateral Habenula Circuitry Drives Reflexive Aversion And Suppresses Feeding Behavior, Jessica L Swanson, Joshua Ortiz-Guzman, Snigdha Srivastava, Pey-Shyuan Chin, Sean W Dooling, Elizabeth Hanson Moss, Mikhail Y Kochukov, Patrick J Hunt, Jay M Patel, Brandon T Pekarek, Qingchun Tong, Benjamin R Arenkiel

Faculty, Staff and Student Publications

Environmental cues and internal states such as mood, reward, or aversion directly influence feeding behaviors beyond homeostatic necessity. The hypothalamus has been extensively investigated for its role in homeostatic feeding. However, many of the neural circuits that drive more complex, non-homeostatic feeding that integrate valence and sensory cues (such as taste and smell) remain unknown. Here, we describe a basal forebrain (BF)-to-lateral habenula (LHb) circuit that directly modulates non-homeostatic feeding behavior. Using viral-mediated circuit mapping, we identified a population of glutamatergic neurons within the BF that project to the LHb, which responds to diverse sensory cues, including aversive and food-related …

Concurrent Mutations In Sf3b1 And Phf6 In Myeloid Neoplasms, Zhuang Zuo, L Jeffrey Medeiros, Sofia Garces, Mark J Routbort, Chi Young Ok, Sanam Loghavi, Rashmi Kanagal-Shamanna, Fatima Zahra Jelloul, Guillermo Garcia-Manero, Kelly S Chien, Keyur P Patel, Rajyalakshmi Luthra, C Cameron Yin

Faculty, Staff and Student Publications

It has been reported that gene mutations in SF3B1 and PHF6 are mutually exclusive. However, this observation has never been rigorously assessed. We report the clinicopathologic and molecular genetic features of 21 cases of myeloid neoplasms with double mutations in SF3B1 and PHF6, including 9 (43%) with myelodysplastic syndrome, 5 (24%) with acute myeloid leukemia, 4 (19%) with myeloproliferative neoplasms, and 3 (14%) with myelodysplastic/myeloproliferative neoplasms. Multilineage dysplasia with ring sideroblasts, increased blasts, and myelofibrosis are common morphologic findings. All cases but one had diploid or non-complex karyotypes. SF3B1 mutations were detected in the first analysis of all the …

Kras Inhibitor That Simultaneously Inhibits Nucleotide Exchange Activity And Effector Engagement, Cynthia V Pagba, Amit K Gupta, Ali K Naji, Dharini Van Der Hoeven, Kelly Churion, Xiaowen Liang, Jacob Jakubec, Magnus Hook, Yan Zuo, Marisela Martinez De Kraatz, Jeffrey A Frost, Alemayehu A Gorfe

Faculty, Staff and Student Publications

We describe a small molecule ligand ACA-14 (2-hydroxy-5-{[(2-phenylcyclopropyl) carbonyl] amino} benzoic acid) as an initial lead for the development of direct inhibitors of KRAS, a notoriously difficult anticancer drug target. We show that the compound binds to KRAS near the switch regions with affinities in the low micromolar range and exerts different effects on KRAS interactions with binding partners. Specifically, ACA-14 impedes the interaction of KRAS with its effector Raf and reduces both intrinsic and SOS-mediated nucleotide exchange rates. Likely as a result of these effects, ACA-14 inhibits signal transduction through the MAPK pathway in cells expressing mutant KRAS and …

Dissecting The Recruitment And Self-Organization Of Αsma-Positive Fibroblasts In The Foreign Body Response, Maria Parlani, Matthew L Bedell, Antonios G Mikos, Peter Friedl, Eleonora Dondossola

Faculty, Staff and Student Publications

The foreign body response (FBR) is a clinically relevant issue that can cause malfunction of implanted medical devices by fibrotic encapsulation. Whereas inflammatory aspects of the FBR have been established, underlying fibroblast-dependent mechanisms remain unclear. We here combine multiphoton microscopy with ad hoc reporter mice expressing α-smooth muscle actin (αSMA) protein to determine the locoregional fibroblast dynamics, activation, and fibrotic encapsulation of polymeric materials. Fibroblasts invaded as individual cells and established a multicellular network, which transited to a two-compartment fibrotic response displaying an αSMA cold external capsule and a long-lasting, inner αSMA hot environment. The recruitment of fibroblasts and extent …

Pleiomorphism Plurihormonal Pit-1-Positive Macroadenoma With Central Hyperthyroidism: A Rare Case Report And Literature Review, Guiliang Peng, Chuanhong Guo, Yangfan Lv, Dandan Li, Ling Zhou, Rufei Shen, Yong Chen, Xin Zheng, Zheng Sun, Hongting Zheng, Min Long

Faculty, Staff and Students Publications

BACKGROUND: Thyrotropin-secreting pituitary neuroendocrine tumors (PitNETs) are rare pituitary adenomas that are occasionally accompanied by hypersecretion of other anterior pituitary hormones, such as growth hormone (GH) and prolactin (PRL). The clinical, biochemical, and pathological characteristics may represent diverse circumstances.

CASE PRESENTATION: In this report, a 33-year-old female diagnosed with a TSH PitNET co-secreting GH presented no obvious clinical symptoms. The main characteristics were elevated thyroid-stimulating hormone (TSH), free tri-iodothyronine (FT3), and free thyroxine (FT4) levels accompanied by slightly elevated GH and insulin-like growth factor-1 (IGF-1) levels. Magnetic resonance imaging (MRI) detected a pituitary macroadenoma (18 × 16 × 16 mm) …

Patient-Centered Outcomes Of An Emergency Department Social And Medical Resource Intervention, Rohit Gupta, Anthony Wang, Daniel Wang, Daniela Ortiz, Karen Kurian, Thiago Halmer, Michael S Jaung

Faculty, Staff and Students Publications

INTRODUCTION: Few studies have examined the impact of emergency department (ED) social interventions on patient outcomes and revisits, especially in underserved populations. Our objective in this study was to characterize a volunteer initiative that provided community medical and social resources at ED discharge and its effect on ED revisit rates and adherence to follow-up appointments at a large, county hospital ED.

METHODS: We performed a cross-sectional analysis of ED patients who received medical and social resources and an educational intervention at discharge between September 2017-June 2018. Demographic information, the number of ED return visits, and outpatient follow-up appointment adherence within …

Impact Of Covid-19 On A Worksite Weight Loss Program For Employees With Overweight And Obesity, Che Young Lee, Michael C Robertson, Kendahl Servino, Thuan Le, Margaret Raber, Katherine Oestman, Karen M Basen-Engquist

Faculty, Staff and Students Publications

OBJECTIVE: The COVID-19 pandemic has been shown to be negatively associated with physical activity engagement, adherence to healthy diet, and weight management among people with obesity. The current study examined COVID-19-related changes in weight, physical activity (PA), and diet among employees with obesity or overweight who participated in Vibrant Lives (VL), a worksite weight loss program.

METHODS: School district employees participated in the 6-month VL weight loss program and were categorized into non-COVID-era participants and COVID-era participants. Participants completed questionnaires about PA and dietary intake at baseline and follow-up. COVID-era participants reported the effects of pandemic on their behaviors. Changes …

Fetal Brain Tumors, A Challenge In Prenatal Diagnosis, Counselling, And Therapy, Ivonne Alexandra Bedei, Thierry A G M Huisman, William Whitehead, Roland Axt-Fliedner, Michael Belfort, Magdalena Sanz Cortes

Faculty, Staff and Students Publications

Fetal brain tumors are a rare entity with an overall guarded prognosis. About 10% of congenital brain tumors are diagnosed during fetal life. They differ from the postnatally encountered pediatric brain tumors with respect to location and tumor type. Fetal brain tumors can be benign or malignant and infiltrate or displace adjacent brain structures. Due to their high mitotic rate, they can show rapid growth. Outcome depends on age of diagnosis, size, and histological tumor type. Findings like polyhydramnios and macrocephaly encountered on routine ultrasound are frequently associated. Detailed prenatal anomaly scan and subsequent fetal magnetic resonance imaging (MRI) may …

Systemic Delivery Of Divalent Europium From Ligand Screening With Implications To Direct Imaging Of Hypoxia, Md Mamunur Rashid, Brooke A Corbin, Pavan Jella, Caitlyn J Ortiz, Md Abul Hassan Samee, Robia G Pautler, Matthew J Allen

Faculty, Staff and Students Publications

Hypoxia is a hallmark of many diseases, including cancer, arthritis, heart and kidney diseases, and diabetes, and it is often associated with disease aggressiveness and poor prognosis. Consequently, there is a critical need for imaging hypoxia in a noninvasive and direct way to diagnose, stage, and monitor the treatment and development of new therapies for these diseases. Eu-containing contrast agents for magnetic resonance imaging have demonstrated potential for in vivo imaging of hypoxia via changes in metal oxidation state from +2 to +3, but rapid oxidation in blood limits EuII-containing complexes to only studies compatible with direct injection to sites. …

Author Correction: A Nanoengineered Topical Transmucosal Cisplatin Delivery System Induces Anti-Tumor Response In Animal Models And Patients With Oral Cancer, Manijeh Goldberg, Aaron Manzi, Amritpreet Birdi, Brandon Laporte, Peter Conway, Stefanie Cantin, Vasudha Mishra, Alka Singh, Alexander T Pearson, Eric R Goldberg, Sam Goldberger, Benjamin Flaum, Rifat Hasina, Nyall R London, Gary L Gallia, Chetan Bettegowda, Simon Young, Vlad Sandulache, James Melville, Jonathan Shun, Sonya E O'Neill, Erkin Aydin, Alex Zhavoronkov, Anxo Vidal, Atenea Soto, Maria Jose Alonso, Ari J Rosenberg, Mark W Lingen, Anil D'Cruz, Nishant Agrawal, Evgeny Izumchenko

Faculty, Staff and Student Publications

No abstract provided.

The Microbial Etiology Of Community-Acquired Pneumonia In Adults: From Classical Bacteriology To Host Transcriptional Signatures, Naomi J Gadsby, Daniel M Musher

Faculty, Staff and Students Publications

All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called "community-acquired pneumonia") beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis,

Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current E, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder

Nebraska Center for Virology: Faculty Publications

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts to reduce the potential for emergence …

Does Receiving A Sars-Cov-2 Antibody Test Result Change Covid-19 Protective Behaviors? Testing Risk Compensation In Undergraduate Students With A Randomized Controlled Trial, Christina Ludema, Molly S Rosenberg, Jonathan T Macy, Sina Kianersi, Maya Luetke, Chen Chen, Lilian Golzarri-Arroyo, Erin Ables, Kevin Maki, David B Allison

Children’s Nutrition Research Center Staff Publications

Background: Risk compensation, or matching behavior to a perceived level of acceptable risk, can blunt the effectiveness of public health interventions. One area of possible risk compensation during the SARS-CoV-2 pandemic is antibody testing. While antibody tests are imperfect measures of immunity, results may influence risk perception and individual preventive actions. We conducted a randomized control trial to assess whether receiving antibody test results changed SARS-CoV-2 protective behaviors.

Purpose: Assess whether objective information about antibody status, particularly for those who are antibody negative and likely still susceptible to SARS-CoV-2 infection, increases protective behaviors. Secondarily, assess whether a positive antibody test …

Spatial Heterogeneity Of Infiltrating T Cells In High-Grade Serous Ovarian Cancer Revealed By Multi-Omics Analysis, Bin Yang, Xiong Li, Wei Zhang, Junpeng Fan, Yong Zhou, Wenting Li, Jingjing Yin, Xiaohang Yang, Ensong Guo, Xi Li, Yu Fu, Si Liu, Dianxing Hu, Xu Qin, Yingyu Dou, Rourou Xiao, Funian Lu, Zizhuo Wang, Tianyu Qin, Wei Wang, Qinghua Zhang, Shuaicheng Li, Ding Ma, Gordon B Mills, Gang Chen, Chaoyang Sun

Faculty, Staff and Student Publications

Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune "cold" patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T …

Structural Insights Into Cardiolipin Replacement By Phosphatidylglycerol In A Cardiolipin-Lacking Yeast Respiratory Supercomplex, Elena G Govorunova, Oleg A Sineshchekov, Leonid S Brown, Ana-Nicoleta Bondar, John L Spudich

Faculty, Staff and Student Publications

Potassium-selective channelrhodopsins (KCRs) are light-gated K+ channels recently found in the stramenopile protist Hyphochytrium catenoides. When expressed in neurons, KCRs enable high-precision optical inhibition of spiking (optogenetic silencing). KCRs are capable of discriminating K+ from Na+ without the conventional K+ selectivity filter found in classical K+ channels. The genome of H. catenoides also encodes a third paralog that is more permeable for Na+ than for K+. To identify structural motifs responsible for the unusual K+ selectivity of KCRs, we systematically analyzed a series of chimeras and mutants of this protein. We found that mutations of three critical residues in the …

Xcvatr: Detection And Characterization Of Variant Impact On The Embeddings Of Single -Cell And Bulk Rna-Sequencing Samples, Arif Harmanci, Akdes Serin Harmanci, Tiemo J Klisch, Akash J Patel

Duncan NRI Faculty and Staff Publications

Background: RNA-sequencing has become a standard tool for analyzing gene activity in bulk samples and at the single-cell level. By increasing sample sizes and cell counts, this technique can uncover substantial information about cellular transcriptional states. Beyond quantification of gene expression, RNA-seq can be used for detecting variants, including single nucleotide polymorphisms, small insertions/deletions, and larger variants, such as copy number variants. Notably, joint analysis of variants with cellular transcriptional states may provide insights into the impact of mutations, especially for complex and heterogeneous samples. However, this analysis is often challenging due to a prohibitively high number of variants and …

The Role Of Lncrnas In The Tumor Microenvironment And Immunotherapy Of Melanoma, Wencheng Zhou, Xuewen Xu, Ying Cen, Junjie Chen

Faculty, Staff and Student Publications

Melanoma is one of the most lethal tumors with highly aggressive and metastatic properties. Although immunotherapy and targeted therapy have certain therapeutic effects in melanoma, a significant proportion of patients still have drug resistance after treatment. Recent studies have shown that long noncoding RNAs (lncRNAs) are widely recognized as regulatory factors in cancer. They can regulate numerous cellular processes, including cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) progression and the immune microenvironment. The role of lncRNAs in malignant tumors has received much attention, whereas the relationship between lncRNAs and melanoma requires further investigation. Our review summarizes tumor suppressive and oncogenic lncRNAs …

Accumulation Of Sublethal Radiation Damage And Its Effect On Cell Survival, Oleg N Vassiliev

Faculty, Staff and Student Publications

Objective. Determine the extent of sublethal radiation damage (SRD) in a cell population that received a given dose of radiation and the impact of this damage on cell survival. Approach. We developed a novel formalism to account for accumulation of SRD with increasing dose. It is based on a very general formula for cell survival that correctly predicts the basic properties of cell survival curves, such as the transition from the linear-quadratic to a linear dependence at high doses. Using this formalism we analyzed extensive experimental data for photons, protons and heavy ions to evaluate model parameters, quantify the extent …

Image Fusion Involving Real-Time Transabdominal Or Endoscopic Ultrasound For Gastrointestinal Malignancies: Review Of Current And Future Applications, Ben S Singh, Irina M Cazacu, Carlos A Deza, Bastien S Rigaud, Adrian Saftoiu, Gabriel Gruionu, Lucian Guionu, Kristy K Brock, Eugene J Koay, Joseph M Herman, Manoop S Bhutani

Faculty, Staff and Student Publications

Image fusion of CT, MRI, and PET with endoscopic ultrasound and transabdominal ultrasound can be promising for GI malignancies as it has the potential to allow for a more precise lesion characterization with higher accuracy in tumor detection, staging, and interventional/image guidance. We conducted a literature review to identify the current possibilities of real-time image fusion involving US with a focus on clinical applications in the management of GI malignancies. Liver applications have been the most extensively investigated, either in experimental or commercially available systems. Real-time US fusion imaging of the liver is gaining more acceptance as it enables further …

Stabilization Of Mcl-1 By E3 Ligase Traf4 Confers Radioresistance, Ming Li, Feng Gao, Xiaoying Li, Yu Gan, Shuangze Han, Xinfang Yu, Haidan Liu, Wei Li

Faculty, Staff and Students Publications

The E3 ligase TNF receptor-associated factor 4 (TRAF4) is frequently overexpressed and closely related to poor prognosis in human malignancies. However, its effect on carcinogenesis and radiosensitivity in oral squamous cell carcinoma (OSCC) remains unclear. The present study found that TRAF4 was significantly upregulated in primary and relapsed OSCC tumor tissues. Depletion of TRAF4 markedly improved the sensitivity of OSCC cells to irradiation (IR) treatment, showing that tumor cell proliferation, colony formation and xenograft tumor growth were reduced. Mechanistically, IR promoted the interaction between TRAF4 and Akt to induce Akt K63-mediated ubiquitination and activation. TRAF4 knockout inhibited the phosphorylation of …

Ccl4 Regulates Eosinophil Activation In Eosiccl4 Regulates Eosinophil Activation In Eosinophilic Airway Inflammationnophilic Airway Inflammation, Hanh Hong Chu, Yoshiki Kobayashi, Dan Van Bui, Yasutaka Yun, Linh Manh Nguyen, Akitoshi Mitani, Kensuke Suzuki, Mikiya Asako, Akira Kanda, Hiroshi Iwai

Faculty, Staff and Student Publications

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory airway disease accompanied by eosinophilic inflammation, the mechanisms of which are unknown. We recently found that CCL4/MIP-1β-a specific ligand for CCR5 receptors-was implicated in eosinophil recruitment into the inflammatory site and was substantially released from activated eosinophils. Moreover, it was found in nasal polyps from patients with ECRS, primarily in epithelial cells. In the present study, the role of epithelial cell-derived CCL4 in eosinophil activation was investigated. First, CCL4 expression in nasal polyps from patients with ECRS as well as its role of CCL4 in eosinophilic airway inflammation were investigated in an in …

Nuclear S6k1 Enhances Oncogenic Wnt Signaling By Inducing Wnt/Β-Catenin Transcriptional Complex Formation, Min Gyu Lee, Hwamok Oh, Jong Woo Park, Jueng Soo You, Jeung-Whan Han

Faculty, Staff and Student Publications

Ribosomal protein S6 kinase 1 (S6K1), a key downstream effector of the mammalian target of rapamycin (mTOR), regulates diverse functions, such as cell proliferation, cell growth, and protein synthesis. Because S6K1 was previously known to be localized in the cytoplasm, its function has been mainly studied in the cytoplasm. However, the nuclear localization and function of S6K1 have recently been elucidated and other nuclear functions are expected to exist but remain elusive. Here, we show a novel nuclear role of S6K1 in regulating the expression of the Wnt target genes. Upon activation of the Wnt signaling, S6K1 translocated from the …

Ex Vivo Drug Sensitivity Correlates With Clinical Response And Supports Personalized Therapy In Pediatric Aml, Debbie C Strachan, Christine J Gu, Ryosuke Kita, Erica K Anderson, Michelle A Richardson, George Yam, Graham Pimm, Jordan Roselli, Alyssa Schweickert, Maci Terrell, Raushan Rashid, Alan K Gonzalez, Hailey H Oviedo, Michelle C Alozie, Tamilini Ilangovan, Andrea N Marcogliese, Hiroomi Tada, Marianne T Santaguida, Alexandra M Stevens

Faculty, Staff and Students Publications

Acute myeloid leukemia (AML) is a heterogeneous disease that accounts for ~20% of all childhood leukemias, and more than 40% of children with AML relapse within three years of diagnosis. Although recent efforts have focused on developing a precise medicine-based approach towards treating AML in adults, there remains a critical gap in therapies designed specifically for children. Here, we present ex vivo drug sensitivity profiles for children with de novo AML using an automated flow cytometry platform. Fresh diagnostic blood or bone marrow aspirate samples were screened for sensitivity in response to 78 dose conditions by measuring the reduction in …