Digital Commons Network^™

Algorithm-Based Meta-Analysis Reveals The Mechanistic Interaction Of The Tumor Suppressor Limd1 With Non-Small-Cell Lung Carcinoma, Ling Wang, Ayrianna Sparks-Wallace, Jared L. Casteel, Mary E.A. Howell, Shunbin Ning

ETSU Faculty Works

Non-small-cell lung carcinoma (NSCLC) is the major type of lung cancer, which is among the leading causes of cancer-related deaths worldwide. LIMD1 was previously identified as a tumor suppressor in lung cancer, but their detailed interaction in this setting remains unclear. In this study, we have carried out multiple genome-wide bioinformatic analyses for a comprehensive understanding of LIMD1 in NSCLC, using various online algorithm platforms that have been built for mega databases derived from both clinical and cell line samples. Our results indicate that LIMD1 expression level is significantly downregulated at both mRNA and protein levels in both lung adenocarcinoma …

2021-March-30-Dr Michael Kruppa Awarded Etsus First Candida Auris-Related Grant, University Marketing And Communication, East Tennessee State University

ETSU News

JOHNSON CITY (March 30, 2021) – Dr. Michael Kruppa, an East Tennessee State University Quillen College of Medicine faculty member, has received a grant to study a global emerging fungal infection, Candida auris.

The National Institutes of Health, National Institute of Allergy and Infectious Disease, awarded a R21 grant to Kruppa for his study “Genetic Characterization of phosphomannan biosynthesis in C. auris.”  The two-year, $407,000 award is the first grant awarded to a researcher at ETSU to study Candida auris.

The incidence of Candida auris, a newly emergent species, has risen worldwide since its first recognition …

2021 March 16 - Medical Student Education Committee Minutes, Medical Student Education Committee, East Tennessee State University

Medical Student Education Committee Minutes

No abstract provided.

Long Non-Coding Rna Gas5 Regulates T Cell Functions Via Mir21-Mediated Signaling In People Living With Hiv, Lam N. T. Nguyen, Lam N. Nguyen, Juan Zhao, Madison Schank, Xindi Dang, Dechao Cao, Sushant Khanal, Bal K. Chand Thakuri, Zeyuan Lu, Jinyu Zhang, Zhengke Li, Zheng D. Morrison, Xiao Y. Wu, Mohamed El Gazzar, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

T cells are critical for the control of viral infections and T cell responses are regulated by a dynamic network of non-coding RNAs, including microRNAs (miR) and long non-coding RNAs (lncRNA). Here we show that an activation-induced decline of lncRNA growth arrest-specific transcript 5 (GAS5) activates DNA damage response (DDR), and regulates cellular functions and apoptosis in CD4 T cells derived from people living with HIV (PLHIV) via upregulation of miR-21. Notably, GAS5-miR21-mediated DDR and T cell dysfunction are observed in PLHIV on antiretroviral therapy (ART), who often exhibit immune activation due to low-grade inflammation despite robust virologic control. We …

2021-March-01-One Year Later - Etsu Responds To Covid-19, University Marketing And Communication, East Tennessee State University

ETSU News

A look back at the first year of the COVID-19 pandemic shows the many ways that East Tennessee State University prioritized the health and safety of the campus community while continuing to serve its students and the Appalachian Highlands community. A COVID-19 Medical Response Team was formed to make recommendations to university administration regarding modifications to campus operations, and a Future Operations Workgroup developed a series of operational stages to provide levels of restrictions and other health and safety guidelines. The Bucs are Back website was created  and continues to keep the campus community informed of new protocols, testing initiatives, …

2021 February 16 - Medical Student Education Committee Minutes, Medical Student Education Committee, East Tennessee State University

Medical Student Education Committee Minutes

No abstract provided.

A Matter Of Life Or Death: Productively Infected And Bystander Cd4 T Cells In Early Hiv Infection, Dechao Cao, Sushant Khanal, Ling Wang, Zhengke Li, Juan Zhao, Lam N. Nguyen, Lam N. Nguyen, Xindi Dang, Madison Schank, Bal K. C. Thakuri, Jinyu Zhang, Zeyuan Lu, Xiao Y. Wu, Zheng D. Morrison, Mohamed El Gazzar, Shunbin Ning, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

CD4 T cell death or survival following initial HIV infection is crucial for the development of viral reservoirs and latent infection, making its evaluation critical in devising strategies for HIV cure. Here we infected primary CD4 T cells with a wild-type HIV-1 and investigated the death and survival mechanisms in productively infected and bystander cells during early HIV infection. We found that HIV-infected cells exhibited increased programmed cell death, such as apoptosis, pyroptosis, and ferroptosis, than uninfected cells. However, productively infected (p24+) cells and bystander (p24-) cells displayed different patterns of cell death due to differential expression of pro-/anti-apoptotic proteins …

2021-February-10-Quillen College Of Medicine Students Gain Covid- Research Experience, University Marketing And Communication, East Tennessee State University

ETSU News

JOHNSON CITY (Feb. 10, 2021) – A summer research program at East Tennessee State University’s Quillen College of Medicine led to an opportunity for medical students to gain COVID-19 research experience.

Dr. Donald Hoover, professor in the Department of Biomedical Sciences, mentored two second-year medical students, Fulton Robinson and Ryan Mihealsick, during Quillen’s Medical Student Summer Research Program held last summer. The students had the opportunity to participate in the conception, planning, implementation and publication of research focusing on cardiac morbidity and mortality related to COVID-19 infection.  

Their mini-review, “Role of angiotensin-converting enzyme 2 and pericytes in cardiac complications of …

2021-February-05-College Of Public Health Hosts Webinar On Vaccines, University Marketing And Communication, East Tennessee State University

ETSU News

Leading Voices in Public Health

JOHNSON CITY (Feb. 5, 2021)  – As the nation moves through the vaccination phases of the coronavirus pandemic, East Tennessee State University’s College of Public Health is hosting a second installment of its popular “Coronavirus: Separating Fact from Fiction” webinar. This installment will focus solely on issues and questions related to the COVID-19 vaccines.

The webinar, which is part of the college’s Leading Voices in Public Health lecture series, will be …

Hiv-1 Latency And Viral Reservoirs: Existing Reversal Approaches And Potential Technologies, Targets, And Pathways Involved In Hiv Latency Studies, Sushant Khanal, Madison Schank, Mohamed El Gazzar, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Eradication of latent human immunodeficiency virus (HIV) infection is a global health challenge. Reactivation of HIV latency and killing of virus-infected cells, the so-called “kick and kill” or “shock and kill” approaches, are a popular strategy for HIV cure. While antiretroviral therapy (ART) halts HIV replication by targeting multiple steps in the HIV life cycle, including viral entry, integration, replication, and production, it cannot get rid of the occult provirus incorporated into the host-cell genome. These latent proviruses are replication-competent and can rebound in cases of ART interruption or cessation. In general, a very small population of cells harbor provirus, …

Trimming Type I Interferon-Mediated Innate Immune Response In Antiviral And Antitumor Defense, Ling Wang, Shunbin Ning

ETSU Faculty Works

The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination-or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunother-apeutic strategies for immune diseases and cancers. Given their importance in antiviral immune response, viruses have evolved sophisticated immune escape …

Gattonrx Magazine - 2021, Bill Gatton College Of Pharmacy, East Tennessee State University

GattonRX Magazine

No abstract provided.

Etsu Health Annual Report - 2021, 2021

ETSU Health Annual Reports

No abstract provided.

Lactate Promotes Macrophage Hmgb1 Lactylation, Acetylation, And Exosomal Release In Polymicrobial Sepsis, Kun Yang, Min Fan, Xiaohui Wang, Jingjing Xu, Yana Wang, Fei Tu, P. S. Gill, Tuanzhu Ha, Li Liu, David L. Williams, Chuanfu Li

ETSU Faculty Works

High circulating levels of lactate and high mobility group box-1 (HMGB1) are associated with the severity and mortality of sepsis. However, it is unclear whether lactate could promote HMGB1 release during sepsis. The present study demonstrated a novel role of lactate in HMGB1 lactylation and acetylation in macrophages during polymicrobial sepsis. We found that macrophages can uptake extracellular lactate via monocarboxylate transporters (MCTs) to promote HMGB1 lactylation via a p300/CBP-dependent mechanism. We also observed that lactate stimulates HMGB1 acetylation by Hippo/YAP-mediated suppression of deacetylase SIRT1 and β-arrestin2-mediated recruitment of acetylases p300/CBP to the nucleus via G protein-coupled receptor 81 (GPR81). …

The Impact Of Hiv-And Art-Induced Mitochondrial Dysfunction In Cellular Senescence And Aging, Madison Schank, Juan Zhao, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

According to the WHO, 38 million individuals were living with human immunodeficiency virus (HIV), 25.4 million of which were using antiretroviral therapy (ART) at the end of 2019. Despite ART-mediated suppression of viral replication, ART is not a cure and is associated with viral persistence, residual inflammation, and metabolic disturbances. Indeed, due to the presence of viral reservoirs, lifelong ART therapy is required to control viremia and prevent disease progression into acquired immune deficiency syndrome (AIDS). Successful ART treatment allows people living with HIV (PLHIV) to achieve a similar life expectancy to uninfected individuals. However, recent studies have illustrated the …

Hydroxychloroquine: A Comprehensive Review And Its Controversial Role In Coronavirus Disease 2019, Pankaj Bansal, Amandeep Goyal, Austin Cusick, Shubham Lahan, Harpal S. Dhaliwal, Poonam Bhyan, Pradnya B. Bhattad, Fawad Aslam, Sagar Ranka, Tarun Dalia, Lovely Chhabra, Devang Sanghavi, Bhavin Sonani, John M. Davis

ETSU Faculty Works

Hydroxychloroquine, initially used as an antimalarial, is used as an immunomodulatory and anti-inflammatory agent for the management of autoimmune and rheumatic diseases such as systemic lupus erythematosus. Lately, there has been interest in its potential efficacy against severe acute respiratory syndrome coronavirus 2, with several speculated mechanisms. The purpose of this review is to elaborate on the mechanisms surrounding hydroxychloroquine. The review is an in-depth analysis of the antimalarial, immunomodulatory, and antiviral mechanisms of hydroxychloroquine, with detailed and novel pictorial explanations. The mechanisms of hydroxychloroquine are related to potential cardiotoxic manifestations and demonstrate potential adverse effects when used for coronavirus …

Selective Oxidative Stress Induces Dual Damage To Telomeres And Mitochondria In Human T Cells, Ling Wang, Zeyuan Lu, Juan Zhao, Madison Schank, Dechao Cao, Xindi Dang, Lam N. Nguyen, Lam N. Nguyen, Sushant Khanal, Jinyu Zhang, Xiao Y. Wu, Mohamed El Gazzar, Shunbin Ning, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere erosion and mitochondrial injury, leading to impaired cellular functions and cell death. Whether oxidative stress-mediated telomere erosion induces mitochondrial injury, or vice versa, in human T cells—the major effectors of host adaptive immunity against infection and malignancy—is poorly understood due to the pleiotropic effects of ROS. Here we employed a novel chemoptogenetic tool that selectively produces a single oxygen (1O2) only at telomeres or mitochondria in Jurkat T cells. We found that targeted 1O2 production at telomeres triggered not only telomeric DNA damage but also mitochondrial dysfunction, resulting in …

State Of The University Annual Report - 2020-2021, Office Of The President, East Tennessee State University, University Marketing And Communication, East Tennessee State University

Office of the President State of the University Annual Report

No abstract provided.

Hcv-Associated Exosomes Upregulate Runxor And Runx1 Expressions To Promote Mdsc Expansion And Suppressive Functions Through Stat3-Mir124 Axis, Bal Krishna Chand Thakuri, Jinyu Zhang, Juan Zhao, Lam N. Nguyen, Lam N.T. Nguyen, Madison Schank, Sushant Khanal, Xindi Dang, Dechao Cao, Zeyuan Lu, Xiao Y. Wu, Yong Jiang, Mohamed El Gazzar, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

RUNX1 overlapping RNA (RUNXOR) is a long non-coding RNA and plays a pivotal role in the differentiation of myeloid cells via targeting runt-related transcription factor 1 (RUNX1). We and others have previously reported that myeloid-derived suppressor cells (MDSCs) expand and inhibit host immune responses during chronic viral infections; however, the mechanisms responsible for MDSC differentiation and suppressive functions, in particular the role of RUNXOR-RUNX1, remain unclear. Here, we demonstrated that RUNXOR and RUNX1 expressions are significantly upregulated and associated with elevated levels of immunosuppressive molecules, such as arginase 1 (Arg1), inducible nitric oxide synthase (iNOS), signal transducer and activator of …

2020-December-02-Dr Jonathan Moorman Receives Va Grant To Study Covid-19, University Marketing And Communication, East Tennessee State University

ETSU News

JOHNSON CITY (Dec. 2, 2020) – Dr. Jonathan Moorman of East Tennessee State University was recently awarded a $330,000 Biomedical Laboratory Research and Development Merit Review Award by the Department of Veterans Affairs to study immune responses to COVID-19. 

The project, “Characterizing trained immune responses to COVID-19,” was one of 18 funded studies awarded from a pool of 104 applications received from VA Medical Centers across the country.

“The new project’s goals are to determine the importance of innate immune responses in responding to repeat exposure to viral antigens following COVID-19 recovery and  identify ‘trained’ innate immune memory responses to …

2020-December-02-Duncan Serving On Nasem, University Marketing And Communication, East Tennessee State University

ETSU News

JOHNSON CITY – (Dec. 2, 2020) Dr. William Duncan, vice provost for research at East Tennessee State University, has been named by the National Academies of Sciences, Engineering, and Medicine (NASEM) to its committee on Assessment of NIH Research on Autoimmune Diseases.

He and the other committee members have been charged with providing a general overview of epidemiologic trends in autoimmune diseases, with particular focus on the research efforts by the National Institutes of Health.  They will be closely examining the NIH research portfolio with particular attention to issues such as risk factors, diagnostic tools, barriers to diagnoses, treatments and …

Using Expanded Natural Killer Cells As Therapy For Invasive Aspergillosis, Win Mar Soe, Joan Hui Juan Lim, David L. Williams, Jessamine Geraldine Goh, Zhaohong Tan, Qi Hui Sam, Sanjay H. Chotirmall, Nur A’Tikah Binte Mohamed Ali, Soo Chin Lee, Ju Ee Seet, Sharada Ravikumar, Louis Yi Ann Chai

ETSU Faculty Works

Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was …

Assessing Nurse Practitioners' Knowledge And Clinical Practice With Regard To The Oral-Systemic Link, Angela Haynes

Electronic Theses and Dissertations

Nurse Practitioners (NPs) comprise a significant portion of the U.S. primary care workforce and play an essential role in patients' health awareness, prevention strategies, disease management, and in providing appropriate provider referrals. Nurse Practitioners receive education on the oral-systemic connection, yet there have been limited studies on the clinical practice of NPs assessing the oral cavity to evaluate the condition of the teeth and the oral tissues. The purpose of this study was to explore the nurse practitioners’ knowledge and practice habits of assessing the oral cavity for diseases or abnormalities in the mouth that can, in turn, affect overall …

Immune Activation Induces Telomeric Dna Damage, Reduces Memory Precursors, And Promotes Short-Lived Effector T Cell Differentiation In Chronic Hcv Infection, Lam Nguyen

Electronic Theses and Dissertations

Chronic hepatitis C virus (HCV) infection exhibits persistent high viral load, inducing T cells differentiation and dysfunction in chronically infected individuals. Recent longitude studies in both HCV specific- and bulk T cells reveal that chronic immune stimulation is the driving force for the impaired T cell functions, however, the underlying mechanisms remain elusive. Here, we show that peripheral CD4⁺ T cells from chronically HCV-infected patients exhibit lymphopenia with the reduction of naïve population and expansion of effector memory T cells. CD4⁺ T cells from HCV patient also display elevated activation markers. including HLA-DR, GLUT1, Granzyme B, and short-lived …

“Fetch M’Dear”: Healers, Midwives, Witches, And Conjuring Women In Select Ya And Toni Morrison Novels, Diane Mallett-Birkitt

Electronic Theses and Dissertations

Accusations and persecution of witchcraft have been embedded in global culture for centuries. For as long as these persecutions have occurred, women have found themselves accused most frequently. Older women with herbal knowledge were often called on to assist with childbirth or termination of pregnancies and this “secret knowledge” often led them to be suspected of supernatural abilities, often of a satanic nature. Intrigued by these wise women who appeared to have mysterious powers and a penchant for arousing the ire of men in the legal, medical, and religious communities, I began to notice their frequent appearance in novels. Does …

2020-October-21-Coronavirus Separating Fact From Fiction Set For Oct 27.Pdf, University Marketing And Communication, East Tennessee State University

ETSU News

JOHNSON CITY (Oct. 21, 2020) – East Tennessee State University’s College of Public Health is hosting “Coronavirus: Separating Fact from Fiction,” a presentation and question and answer session featuring three local experts on infectious diseases and public health.

The event, which is part of the college’s Leading Voices in Public Health lecture series, will be held on Tuesday, Oct. 27 from 6-7 p.m. on Zoom. It is free and open to the public.

Dr. Randy Wykoff, dean of the ETSU College of Public Health, will be joined by Dr. Jonathan Moorman, vice chair of research and scholarship, professor and chief …

2020-October-12-Dr Chuanfu Li Receives 2 Million Nih Grant.Pdf, University Marketing And Communication, East Tennessee State University

ETSU News

JOHNSON CITY (Oct. 12, 2020) – The National Institutes of Health (NIH) has awarded East Tennessee State University’s Dr. Chuanfu Li a $2.19 million R01 grant to research the role of lactate in sepsis-induced cardiovascular dysfunction.

Li is a professor in the Department of Surgery at Quillen College of Medicine and is also a member of the ETSU Center of Excellence in Inflammation, Infectious Disease, and Immunity (CIIDI). He was recently named one of the inaugural Quillen Distinguished Research Fellows.

Li and his laboratory group have made a novel discovery that high levels of lactate directly cause vascular dysfunction and …

Lactate Suppresses Macrophage Pro-Inflammatory Response To Lps Stimulation By Inhibition Of Yap And Nf-Κb Activation Via Gpr81-Mediated Signaling, Kun Yang, Jingjing Xu, Min Fan, Fei Tu, Xiaohui Wang, Tuanzhu Ha, David L. Williams, Chuanfu Li

ETSU Faculty Works

Recent evidence from cancer research indicates that lactate exerts a suppressive effect on innate immune responses in cancer. This study investigated the mechanisms by which lactate suppresses macrophage pro-inflammatory responses. Macrophages [Raw 264.7 and bone marrow derived macrophages (BMDMs)] were treated with LPS in the presence or absence of lactate. Pro-inflammatory cytokines, NF-κB and YAP activation and nuclear translocation were examined. Our results show that lactate significantly attenuates LPS stimulated macrophage TNF-α and IL-6 production. Lactate also suppresses LPS stimulated macrophage NF-κB and YAP activation and nuclear translocation in macrophages. Interestingly, YAP activation and nuclear translocation are required for LPS …

2020-October-01-Etsu Health Receives Cup Of Kindness Award For Community Service.Pdf, University Marketing And Communication, East Tennessee State University

ETSU News

Highlights of Community Service

Early in the pandemic, ETSU Health worked to established the region’s first drive-through COVID-19 testing site. This site was instrumental in detecting the first cases of community spread in the area. Currently, ETSU’s Quillen College of Medicine is conducting vital research on COVID-19 using blood samples from local patients who have recovered from the disease.

As the pandemic progressed, ETSU Health became a go-to source of expertise for government and community leaders, our local media, and the public. Representatives from ETSU Health were called upon for interviews about various facets of COVID-19, and the ETSU College …

A Baker’S Dozen Of Top Antimicrobial Stewardship Intervention Publications In 2019, Kayla R. Stover, Elias B. Chahine, David Cluck, Sarah Green, Daniel B. Chastain, Darrell Childress, Carmen Faulkner-Fennell, Katherine Lusardi, Edoabasi U. Mcgee, Michelle Turner, P. Brandon Bookstaver, Christopher M. Bland

ETSU Faculty Works

Staying current on literature related to antimicrobial stewardship can be challenging given the ever-increasing number of published articles. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship–related peer-reviewed literature that detailed an actionable intervention for 2019. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training and to identify potential intervention opportunities within one’s institution.