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Editorial: Immunological Aspects Of Emerging And Re-Emerging Zoonoses, Wei Wang, Jingxin Li, Yuejin Liang, Wenping Gong

Faculty, Staff and Student Publications

No abstract provided.

An Image-Driven Micromechanical Approach To Characterize Multiscale Remodeling In Infarcted Myocardium, Emilio A Mendiola, Sunder Neelakantan, Qian Xiang, Shuda Xia, Jianyi Zhang, Vahid Serpooshan, Peter Vanderslice, Reza Avazmohammadi

Faculty, Staff and Student Publications

Myocardial infarction (MI) is accompanied by the formation of a fibrotic scar in the left ventricle (LV) and initiates significant alterations in the architecture and constituents of the LV free wall (LVFW). Previous studies have shown that LV adaptation is highly individual, indicating that the identification of remodeling mechanisms post-MI demands a fully subject-specific approach that can integrate a host of structural alterations at the fiber-level to changes in bulk biomechanical adaptation at the tissue-level. We present an image-driven micromechanical approach to characterize remodeling, assimilating new biaxial mechanical data, histological studies, and digital image correlation data within an in-silico framework …

Her4 And Egfr Activate Cell Signaling In Nrg1 Fusion-Driven Cancers: Implications For Her2-Her3-Specific Versus Pan-Her Targeting Strategies, Hibiki Udagawa, Monique B Nilsson, Jacqulyne P Robichaux, Junqin He, Alissa Poteete, Hong Jiang, Simon Heeke, Yasir Y Elamin, Yuji Shibata, Shingo Matsumoto, Kiyotaka Yoh, Shogo Okazaki, Takashi Masuko, Igor Odintsov, Romel Somwar, Marc Ladanyi, Koichi Goto, John V Heymach

Faculty, Staff and Student Publications

Introduction: NRG1 gene fusions are clinically actionable alterations identified in NSCLC and other tumors. Previous studies have reported that NRG1 fusions signal through HER2 and HER3 but, thus far, strategies targeting HER3 specifically or HER2-HER3 signaling have exhibited modest activity in patients with NSCLC bearing NRG1 fusions. Although NRG1 fusion proteins can bind HER4 in addition to HER3, the contribution of HER4 and other HER family members in NRG1 fusion-positive cancers is not fully understood.

Methods: We investigated the role of HER4 and EGFR-HER3 signaling in NRG1 fusion-positive cancers using Ba/F3 models engineered to express various HER family members in …

Investigation Of Autosegmentation Techniques On T2-Weighted Mri For Off-Line Dose Reconstruction In Mr-Linac Workflow For Head And Neck Cancers, Brigid A Mcdonald, Carlos E Cardenas, Nicolette O'Connell, Sara Ahmed, Mohamed A Naser, Kareem A Wahid, Jiaofeng Xu, Dan Thill, Raed J Zuhour, Shane Mesko, Alexander Augustyn, Samantha M Buszek, Stephen Grant, Bhavana V Chapman, Alexander F Bagley, Renjie He, Abdallah S R Mohamed, John Christodouleas, Kristy K Brock, Clifton D Fuller

Faculty, Staff and Student Publications

Background: In order to accurately accumulate delivered dose for head and neck cancer patients treated with the Adapt to Position workflow on the 1.5T magnetic resonance imaging (MRI)-linear accelerator (MR-linac), the low-resolution T2-weighted MRIs used for daily setup must be segmented to enable reconstruction of the delivered dose at each fraction.

Purpose: In this pilot study, we evaluate various autosegmentation methods for head and neck organs at risk (OARs) on on-board setup MRIs from the MR-linac for off-line reconstruction of delivered dose.

Methods: Seven OARs (parotid glands, submandibular glands, mandible, spinal cord, and brainstem) were contoured on 43 images by …

The Mir-17-92 Cluster In Cardiac Health And Disease, Yuhan Cao, Mingjie Zheng, Maham A Sewani, Jun Wang

Faculty, Staff and Student Publications

MicroRNAs (miRs) are small noncoding RNAs that play important roles in both physiological and pathological processes through post-transcriptional regulation. The miR-17-92 cluster includes six individual members: miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1. The miR-17-92 cluster has been extensively studied and reported to broadly function in cancer biology, immunology, neurology, pulmonology, and cardiology. This review focuses on its roles in heart development and cardiac diseases. We briefly introduce the nature of the miR-17-92 cluster and its crucial roles in both normal development and the pathogenesis of various diseases. We summarize the recent progress in understanding the versatile roles of miR-17-92 …

Generation Of Non-Alloreactive Antiviral Central Memory Cd8 Human Veto T Cells For Cell Therapy, Esther Bachar-Lustig, Assaf Lask, Yaki Eidelstein, Noga Or-Geva, Rotem Gidron-Budovsky, Bar Nathansohn-Levy, Matthias Eyrich, Wei-Hsin Liu, Giang Dang, Karla Castro Miranda, Alejandro Ramirez, Indreshpal Kaur, Katayoun Rezvani, Elizabeth Shpall, Richard E Champlin, Arnon Nagler, Avichai Shimoni, Sivan Barnees-Kagan, Yair Reisner

Faculty, Staff and Student Publications

Previous studies in mice demonstrated that CD8 T cells exhibit marked veto activity enhancing engraftment in several models for T cell-depleted bone marrow (TDBM) allografting. To reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic CD8 veto T cells, these studies made use of naive CD8 T cells stimulated against third-party stimulators under cytokine deprivation and subsequent expansion in the presence of IL-15. More recently, it was shown that mouse CD8 veto T cells can be generated by stimulating CD8 memory T cells from ovalbumin immunized mice under cytokine deprivation, using ovalbumin as a third-party antigen. These cells also …

Emerging Therapeutic Options For Follicular-Derived Thyroid Cancer In The Era Of Immunotherapy, Naimah Turner, Sarah Hamidi, Rim Ouni, Rene Rico, Ying C Henderson, Maria Puche, Sayan Alekseev, Jocelynn G Colunga-Minutti, Mark E Zafereo, Stephen Y Lai, Sang T Kim, Maria E Cabanillas, Roza Nurieva

Faculty, Staff and Student Publications

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also …

Aging-Related Biomarker Discovery In The Era Of Immune Checkpoint Inhibitors For Cancer Patients, Abdullah Al-Danakh, Mohammed Safi, Yuli Jian, Linlin Yang, Xinqing Zhu, Qiwei Chen, Kangkang Yang, Shujing Wang, Jianjun Zhang, Deyong Yang

Faculty, Staff and Student Publications

Older patients with cancer, particularly those over 75 years of age, often experience poorer clinical outcomes compared to younger patients. This can be attributed to age-related comorbidities, weakened immune function, and reduced tolerance to treatment-related adverse effects. In the immune checkpoint inhibitors (ICI) era, age has emerged as an influential factor impacting the discovery of predictive biomarkers for ICI treatment. These age-linked changes in the immune system can influence the composition and functionality of tumor-infiltrating immune cells (TIICs) that play a crucial role in the cancer response. Older patients may have lower levels of TIICs infiltration due to age-related immune …

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Protection Against Fibrosis By A Bacterial Consortium In Metabolic Dysfunction-Associated Steatohepatitis And The Role Of Amino Acid Metabolism, Suet-Ying Kwan, Kristyn A Gonzales, Mohamed A Jamal, Heather L Stevenson, Lin Tan, Philip L Lorenzi, P Andrew Futreal, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Robert R Jenq, Laura Beretta

Faculty, Staff and Student Publications

The gut microbiota drives progression to liver fibrosis, the main determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH). In this study, we aimed to identify bacterial species associated with protection against liver fibrosis in a high-risk population, and test their potential to protect against liver fibrosis in vivo. Based on stool shotgun metagenomic sequencing of 340 subjects from a population cohort disproportionally affected by MASH, we identified bacterial species from the Bacteroidales and Clostridiales orders associated with reduced risk of liver fibrosis. A bacterial consortium was subsequently tested in a mouse model of MASH, which demonstrated protective effects against …

Usp22 Overexpression Fails To Augment Tumor Formation In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Interleukin-1beta And Inflammasome Expression In Spinal Cord Following Chronic Constriction Injury In Male And Female Rats, Suzanne M Green-Fulgham, Jayson B Ball, Andrew J Kwilasz, Michael E Harland, Matthew G Frank, Joseph M Dragavon, Peter M Grace, Linda R Watkins

Faculty, Staff and Student Publications

Females represent a majority of chronic pain patients and show greater inflammatory immune responses in human chronic pain patient populations as well as in animal models of neuropathic pain. Recent discoveries in chronic pain research have revealed sex differences in inflammatory signaling, a key component of sensory pathology in chronic neuropathic pain, inviting more research into the nuances of these sex differences. Here we use the chronic constriction injury (CCI) model to explore similarities and differences in expression and production of Inflammatory cytokine IL-1beta in the lumbar spinal cord, as well as its role in chronic pain. We have discovered …

Identifying Genomic Data Sources From Biomedical Literature, Xu Zuo, Ashley Gilliam, Yan Hu, Kalpana Raja, Kirk Roberts, Hua Xu

Faculty, Staff and Student Publications

Genomic research is becoming increasingly data-intensive, yet the proper reference of data remains a persistent challenge. Despite various efforts to establish and standardize data citation practices, scientists frequently fall short of accurately referencing data in their papers. This deficiency complicates the attribution of contributions to data providers and impedes the reproducibility of findings in genomic research. This study addresses this gap by introducing a gold standard corpus designed to identify mentions of genomic data sources and associated attributes, thereby offering insights into data source availability and accessibility. Within this corpus, we categorize entities into six classes, encompassing three primary entities …

The Contribution Of Amyloid Deposition In The Aortic Valve To Calcification And Aortic Stenosis, Romeesa Khan, Claudia M Di Gesù, Juneyoung Lee, Louise D Mccullough

Faculty, Staff and Student Publications

Trillions of microbes live symbiotically in the host, specifically in mucosal tissues such as the gut. Recent advances in metagenomics and metabolomics have revealed that the gut microbiota plays a critical role in the regulation of host immunity and metabolism, communicating through bidirectional interactions in the microbiota-gut-brain axis (MGBA). The gut microbiota regulates both gut and systemic immunity and contributes to the neurodevelopment and behaviors of the host. With aging, the composition of the microbiota changes, and emerging studies have linked these shifts in microbial populations to age-related neurological diseases (NDs). Preclinical studies have demonstrated that gut microbiota-targeted therapies can …

The Emerging Role Of Notch3 Receptor Signalling In Human Lung Diseases, Grant W Goodman, Patrick Devlin, Bryce E West, Rodney M Ritzel

Faculty, Staff and Student Publications

The recent identification of skull bone marrow as a reactive hematopoietic niche that can contribute to and direct leukocyte trafficking into the meninges and brain has transformed our view of this bone structure from a solid, protective casing to a living, dynamic tissue poised to modulate brain homeostasis and neuroinflammation. This emerging concept may be highly relevant to injuries that directly impact the skull such as in traumatic brain injury (TBI). From mild concussion to severe contusion with skull fracturing, the bone marrow response of this local myeloid cell reservoir has the potential to impact not just the acute inflammatory …

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

Measurement Of 8-Hydroxy-2′-Deoxyguanosine In Serum And Cerebrospinal Fluid Of Horses With Neuroaxonal Degeneration And Other Causes Of Proprioceptive Ataxia, Megan Palmisano, Jeaneen Kulp, Susan Bender, Darko Stefanovski, Mary Robinson, Amy Johnson

Faculty, Staff and Student Publications

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses.

HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses.

ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November …

One-Step Production Of Fully Biotinylated And Glycosylated Human Fc Gamma Receptors, Minhyo Kang, Zening Wang, Xin Ge

Faculty, Staff and Student Publications

Initiating and regulating humoral immunity, Fc gamma receptors (FcγRs) have been identified both as therapeutics and as drug targets, and thus production of biologically active FcγRs is highly demanded for biopharmaceutical development. Focusing on low-affinity FcγRs IIA (131H/R allotypes), IIB, and IIIA (176F/V), this study used human 293-F cells to achieve correct post-translational modifications (PTMs) including biotinylation, N-glycosylation, and disulfides. Approaches involving co-expression of FcγR-AviTag and Escherichia coli biotin ligase BirA, endoplasmic reticulum retention, stable and transient transfections, and optimization of transgene ratio were investigated. Protein electrophoresis under reducing and non-reducing conditions, enzymatic deglycosylation, streptavidin pull-down assays, and binding kinetic …

Persistent Microbial Infections And Idiopathic Pulmonary Fibrosis – An Insight Into Non-Typeable Haemophilus Influenza Pathogenesis, Anthony Shadid, Haydn E Rich, Hunter Devaughn, Aleksey Domozhirov, Marie-Françoise Doursout, Tingting Weng-Mills, Kristin L Eckel-Mahan, Harry Karmouty-Quintana, Marcos I Restrepo, Pooja Shivshankar

Faculty, Staff and Student Publications

Interstitial lung disease (ILD) is characterized by chronic inflammation and scarring of the lungs, of which idiopathic pulmonary fibrosis (IPF) is the most devastating pathologic form. Idiopathic pulmonary fibrosis pathogenesis leads to loss of lung function and eventual death in 50% of patients, making it the leading cause of ILD-associated mortality worldwide. Persistent and subclinical microbial infections are implicated in the acute exacerbation of chronic lung diseases. However, while epidemiological studies have highlighted pollutants, gastric aspirate, and microbial infections as major causes for the progression and exacerbation of IPF, the role of persistent microbial infections in the pathogenesis of IPF …

How Can We Treat If We Do Not Measure: A Systematic Review Of Neurogenic Bowel Objective Measures, Argy Stampas, Amisha Patel, Komal Luthra, Madeline Dicks, Radha Korupolu, Leila Neshatian, George Triadafilopoulos

Faculty, Staff and Student Publications

Background: Guidelines fail to recommend objective measures to assist with treatment of neurogenic bowel dysfunction (NBD) in spinal cord injury (SCI).

Objectives: The main objective was to review the literature to identify the objective measures used in all NBD populations and to present their results and any correlations performed to validated subjective measures.

Methods: A systematic review of the literature was performed in accordance with PRISMA (2020) guidelines, including all records from January 2012 to May 2023 with MeSH terms like "neurogenic bowel" indexed in the following databases: PubMed, EMBASE, CINAHL, Cochrane Central Trials Register, and ClinicalTrials.gov. Abstracts were excluded …

Profound First-Degree Atrioventricular Block In A High-Level Basketball Athlete., Justin D Stumph, William K Cornwell, Michael A Rosenberg, Morteza Khodaee

Heart and Vascular Articles

First-degree atrioventricular (AV) block (PR interval >200 ms) is commonly observed among screening electrocardiogram (ECG) in athletes. Profound first-degree AV block (PR interval >400 ms) and Mobitz type I (Wenckebach) second-degree AV block are generally uncommon and often require further workup on a case-by-case basis, particularly when there is concern for a structural cardiac abnormality. In this case, we present an example of an asymptomatic profound first-degree AV block with Mobitz type I (Wenckebach) second-degree AV block. Transthoracic echocardiogram and stress echocardiogram were unremarkable and the patient was cleared to participate in sports without any restriction. Physicians managing athletes should …

Combining Neuroimaging And Brain Stimulation To Test Alternative Causal Pathways For Nicotine Addiction In Schizophrenia, Xiaoming Du, Fow-Sen Choa, Joshua Chiappelli, Heather Bruce, Mark Kvarta, Ann Summerfelt, Yizhou Ma, William T Regenold, Kevin Walton, George F Wittenberg, Stephanie Hare, Si Gao, Andrew Van Der Vaart, Zhiwei Zhao, Shuo Chen, Peter Kochunov, L Elliot Hong

Faculty, Staff and Student Publications

The smoking rate is high in patients with schizophrenia. Brain stimulation targeting conventional brain circuits associated with nicotine addiction has also yielded mixed results. We aimed to identify alternative circuitries associated with nicotine addiction in both the general population and schizophrenia, and then test whether modulation of such circuitries may alter nicotine addiction behaviors in schizophrenia. In Study I of 40 schizophrenia smokers and 51 non-psychiatric smokers, cross-sectional neuroimaging analysis identified resting state functional connectivity (rsFC) between the dorsomedial prefrontal cortex (dmPFC) and multiple extended amygdala regions to be most robustly associated with nicotine addiction severity in healthy controls and …

Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially …

Willingness To Accept Monkeypox Vaccine And Its Correlates Among Men Who Have Sex With Men In Southern China: A Web-Based Online Cross-Sectional Study, Xinju Huang, Zhifeng Lin, Jiao Qin, Dee Yu, Fei Zhang, Ganggang Fang, Xi Chen, Jinfeng He, Ping Cen, Mu Li, Rongjing Zhang, Tong Luo, Junjun Jiang, Sanqi An, Hao Liang, Li Ye, Bingyu Liang

Faculty, Staff and Student Publications

BACKGROUND: The May 2022 global outbreak of monkeypox (MPX) poses a threat to the health of men who have sex with men. However, there is limited data on the willingness of MSM to receive monkeypox vaccination in Southern China. This study aimed to assess the knowledge of MPX, concerns regarding MPX, and willingness to receive monkeypox vaccination, as well as their correlates, among MSM in China.

METHODS: We conducted a Web-based online survey of MSM in Southern China from August to September 2022. Data were collected on the socio-demographic characteristics, knowledge, worries, concerns regarding MPX and willingness to receive monkeypox …

Voluntary Wheel Running Prevents Formation Of Membrane Attack Complexes And Myelin Degradation After Peripheral Nerve Injury, Suzanne M Green-Fulgham, Michael J Lacagnina, Kendal F Willcox, Jiahe Li, Michael E Harland, Adriano Polican Ciena, Igor R Correia Rocha, Jayson B Ball, Renee A Dreher, Younus A Zuberi, Joseph M Dragavon, Marucia Chacur, Steven F Maier, Linda R Watkins, Peter M Grace

Faculty, Staff and Student Publications

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor …

Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially …

Tissue Transglutaminase: A Multifunctional And Multisite Regulator In Health And Disease, Zhouzhou Yao, Yuhua Fan, Lizhen Lin, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Tissue transglutaminase (TG2) is a widely distributed multifunctional protein involved in a broad range of cellular and metabolic functions carried out in a variety of cellular compartments. In addition to transamidation, TG2 also functions as a Gα signaling protein, a protein disulfide isomerase (PDI), a protein kinase, and a scaffolding protein. In the nucleus, TG2 modifies histones and transcription factors. The PDI function catalyzes the trimerization and activation of heat shock factor-1 in the nucleus and regulates the oxidation state of several mitochondrial complexes. Cytosolic TG2 modifies proteins by the addition of serotonin or other primary amines and in this …

From Mitochondria To Tumor Suppression: Acat1’S Crucial Role In Gastric Cancer, Wei He, Yanfang Li, Song-Bai Liu, Ying Chang, Shiyuan Han, Xingyu Han, Zixin Ma, Hesham M Amin, Yao-Hua Song, Jin Zhou

Faculty, Staff and Student Publications

Acetyl CoA acetyltransferase 1 (ACAT1), a mitochondrial enzyme, is mainly involved in the formation and decomposition of ketones, isoleucine, and fatty acids. Previous clinical studies showed that mutations in the ACAT1 gene lead to ketoacidosis, Notably the role of ACAT1 in human cancer' pathogenesis varies depending on cancer type, and its specific role in gastric cancer remains largely unknown. In the current study, we found that the expression of ACAT1 in primary late-stage gastric cancer tumor tissues was significantly lower than in early-stage tumors. This observation was further confirmed in high-grade gastric cancer cell line MKN45. The expression of CD44 …

Dysregulation Of Epigenetic Modifications In Inborn Errors Of Immunity, Zhongyao Xiao, Rongjing He, Zihan Zhao, Taiping Chen, Zhengzhou Ying

Faculty, Staff and Student Publications

Inborn errors of immunity (IEIs) are a group of typically monogenic disorders characterized by dysfunction in the immune system. Individuals with these disorders experience increased susceptibility to infections, autoimmunity and malignancies due to abnormal immune responses. Epigenetic modifications, including DNA methylation, histone modifications and chromatin remodeling, have been well explored in the regulation of immune cell development and effector function. Aberrant epigenetic modifications can disrupt gene expression profiles crucial for immune responses, resulting in impaired immune cell differentiation and function. Dysregulation of these processes caused by mutations in genes involving in epigenetic modifications has been associated with various IEIs. In …

Usp22 Overexpression Fails To Augment Tumor Formatiaon In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …