Translational Medical Research Commons^™

Activation Of Crtc2/Creb1 In Skeletal Muscle Enhances Weight Loss During Intermittent Fasting, Nelson E Bruno, Jerome C Nwachukwu, David C Hughes, Sathish Srinivasan, Richard Hawkins, David Sturgill, Gordon L Hager, Stephen Hurst, Shey-Shing Sheu, Sue C Bodine, Michael D Conkright, Kendall W Nettles

Department of Medicine Faculty Papers

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating …

Does Hiv Status Confer A Higher Risk Of Acquiring Covid-19? Using Clinical Decision Science To Combat Patients’ Anxiety, Camilo Guzman

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

del Amo J, Polo R, Moreno S, et al. “Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy.” Annals of Internal Medicine. 2020;173(7):536-541. doi.org/10.7326/m20-3689

for a patient with HIV and concerns about COVID-19 for immunocompromised individuals.

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

Generating Cisplatin Resistant Hpv-Positive Hnscc Cell Lines, Temitope Akintola

Undergraduate Student Research Internships Conference

Acquired or innate resistance to chemotherapy poses a significant challenge in the treatment of head and neck squamous cell carcinomas (HNSCC). HNSCCs are often treated with a combination of surgery, radiation and chemotherapy, with cisplatin being a standard-of-care chemotherapy drug. Human Papillomavirus (HPV) associated HNSCCs have better treatment outcomes and prognosis when compared to HPV- HNSCCs. However, a subset (15-20%) of HPV+ patients develop treatment resistant diseases. The purpose of this study is to generate in-vitro models of cisplatin resistance in five HNSCC cell lines. We aim to characterize the generated cells in order to identify target genes that may …

Modulating Immunometabolism To Improve The Activity Of Car-Nk Cells Targeting Cd70 In Renal Cell Carcinoma, Hind Rafei

Dissertations & Theses (Open Access)

Despite the approval of several therapies for metastatic clear cell renal cell carcinoma (ccRCC), disease resistance and relapse are common, and therapies with novel mechanisms of action are urgently needed. Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable responses in hematologic malignancies, but many obstacles hinder success in solid tumors including the paucity of highly specific targets and the hostility of the tumor microenvironment (TME). Moreover, the limitations of generating an autologous cell product, such as cost of manufacture, and the challenges of toxicity with CAR-T cells highlight the need to develop new cell therapy products that are at …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

MSU Graduate Theses

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Post-Acute Sequelae Of Covid-19 (Pasc): Association With Inflammation And Autoimmunity, Raghava S. Ambadapoodi, Fnu Deepti, Javaria Anwer Mbbs, Rafael Fernandez-Botran

The University of Louisville Journal of Respiratory Infections

It has become increasingly evident that a high percentage of patients that recover from acute COVID-19 infection continue to suffer from a variety of persistent symptoms even months after viral clearance, the most common ones being fatigue, dyspnea, anosmia, dysgeusia, cognitive dysfunction, and psychological problems, including anxiety and depression. This syndrome, known as Post-acute sequelae of COVID-19 (PASC), can severely affect the life quality and represents an important health care concern. The exact causes for the symptoms observed in patients with PASC remain to be adequately characterized, but are likely to be associated with multiple factors, including residual disease and/or …

An Update On The Hiv Dna Vaccine Strategy, Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable …

Exploring Attitudes Towards Newly Approved Therapeutics In Prenatal Genetic Counseling Practice, Charlotte Close

Human Genetics Theses

Cystic fibrosis (CF) care has rapidly evolved over the past decade due to the introduction of CFTR modulators and continued quality improvement efforts, yet research from 2013 suggests that prenatal genetic counselors often did not feel knowledgeable discussing newer CF treatments with patients and expressed the need to refer to a CF specialist (Elsas, 2017). Given that the intervening years have allowed for collection of long-term data about CFTR modulators and that the recently approved modulator Trikafta (tez/elx/iva) is available to 90% of the CF population, it is appropriate to re-evaluate the status of prenatal genetic counselors’ awareness of and …

Non-Selective Primary Human Tumor Cell Line Generation From Surgical Resections To Be Paired With Flash Frozen And Paraffin Embedded Tissue: Advancements In Democratizing Translational Research Materials To Rural Institutions, Jennifer Hawkins, Rebecca Russell, Logan M. Lawrence, Amrita Valluri, Jessica Wellman, Krista Denning

Marshall Journal of Medicine

Translational cancer research relies on the availability of human patient tissue demonstrating the specific disease process under investigation. Biobanks of human tissue have historically been and remain to date the primary access point for cancer research samples. Biorepositories routinely supply researchers with varying sample types for use in biomedical studies; most commonly formalin-fixed and paraffin-embedded (FFPE) tissue, or fresh snap-frozen tissue. In conjunction with preserved tissue samples, viable tumor cell lines derived from patient tissue have emerged to be a new gold standard in cancer research particularly in drug discovery and functional prognostic assays. Tissue banks providing these samples are …

Streptococcus Anginosus Lung Infection And Empyema: A Case Report And Review Of The Literature, Nishita Tripathi, Kuldeep Ghosh, Anupama Raghuram

The University of Louisville Journal of Respiratory Infections

Streptococcus milleri group (SMG) also referred to as the Streptococcus anginosus group. These are Gram-positive, variable hemolysis, catalase negative, microaerophilic, non-motile facultative anaerobes which have been known to cause abscesses in humans. We report a case of empyema caused by Streptococcus anginosus in a patient with an unresolved pneumonia for over a month. In early October 2018, the patient presented to an emergency room with the complaints of shortness of air, productive cough, chills, subjective fever and weight loss for 4 weeks. A chest X-ray revealed a left lower lobe pneumonia. He was treated with 250 mg of azithromycin for …

Differential Effects Of Kim-1 In Subcutaneous And Orthotopic Renca Models Of Kidney Cancer, Demitra M. Yotis Dy

Electronic Thesis and Dissertation Repository

Renal Cell Carcinoma (RCC) is the most common and fatal type of kidney cancer. Over 30% of patients that are diagnosed with RCC exhibit metastases. Almost 88% of patients with distant metastases succumb to the disease within 5 years of diagnosis. Kidney Injury Molecule-1 (KIM-1) is a cell surface glycoprotein that is not expressed in a healthy kidney but becomes highly expressed on proximal tubular epithelial cells (PTECs) following injury. Data from the Cancer Genome Atlas (TCGA) reveals that >90% of RCC tumours express KIM-1 mRNA and that higher expression levels correlate with increased overall survival rates of patients. The …

Pvn Activity In Cardiac Sympathetic Afferent Reflex (Csar) Control And Cardiovascular Function, Shane H. Boomer

Honors Thesis

Regulation of blood pressure is essential in bodily health. Hypertension and hypotension can be associated with varying diseases that could potentiate further disease. From this, understanding the mechanisms that regulate blood pressure is important within medicine. In my study, I will be focusing on a cardiovascular reflex that is less well understood, the cardiac sympathetic afferent reflex (CSAR). In particular, this work will examine sex differences in this reflex in overall function and in the involvement of an area of the brain called the paraventricular nucleus (PVN). We will test the hypothesis that there will be a significant difference between …

Functional Role Of Dream And Dyrk1a In High-Grade Serous Ovarian Cancer Cell Dormancy, Pirunthan Perampalam

Electronic Thesis and Dissertation Repository

High-grade serous ovarian cancer (HGSOC) is the most common form of ovarian cancer. The majority of women are disproportionately diagnosed at an advanced stage (stage III-IV) of the disease when tumours have progressed beyond the ovaries or fallopian tubes and into the peritoneal cavity. Survival rates at late-stage are as low as 25% and chemoresistant disease recurrence is common, affecting up to 90% of patients. Multicellular clusters called spheroids contribute to dormancy, chemoresistance, and metastases and are a major challenge to treatment of HGSOC. Spheroid cells undergo reversible quiescence to evade chemotherapy in a process mediated by the mammalian DREAM …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Development Of A Method Using Retrograde Neuronal Tracers To Neuroanatomically Characterize Respiratory Neural Circuitry, Samantha Thomas, Angelo Lepore

Phase 1

Introduction:

Loss of respiratory function is one of the leading causes of death following spinal cord injury (SCI). Existing studies have demonstrated that pre-phrenic interneurons (PPIN’s) can be recruited into the phrenic motor neuron (PhMN) pathway following cervical SCI and may contribute to respiratory recovery, but there is still a lack of information detailing the nature of these changes and the extent they may improve diaphragm function. This project aims to validate a method of utilizing neuronal tracers to further characterize the intact respiratory circuitry.

Methods:

This study was carried out using a rat model. A fluorophore-conjugated retrograde neuronal …

Comparison Of Circulating Tumour Dna And Extracellular Vesicle Dna By Low-Pass Whole-Genome Sequencing Reveals Molecular Drivers Of Disease In A Breast Cancer Patient, Olivia Ruhen, Bob Mirzai, Michael E. Clark, Bella Nguyen, Carlos Salomon, Wendy Erber, Katie Meehan

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. There is increasing recognition of circulating tumour DNA (ctDNA) as a non-invasive alternative to tumour tissue for the molecular characterisation and monitoring of disease. Recent evidence suggests that cancer-associated changes can also be detected in the DNA contained within extracellular vesicles (EVs). As yet, there has been limited investigation into the relationship between EV DNA and ctDNA, and no studies have examined the EV DNA of breast cancer patients. The aim of this study was to use low-pass whole-genome sequencing to identify copy number variants (CNVs) in serial samples of both …