Translational Medical Research Commons^™

Gatad2b O-Glcnacylation Regulates Breast Cancer Stem-Like Potential And Drug Resistance, Giang Le Minh, Jessica Merzy, Emily Esquea, Nusaiba Ahmed, Riley Young, Ryan Sharp, Tejsi Dhameliya, Bernice Agana, Mi-Hye Lee, Jennifer Bethard, Susana Comte-Walters, Lauren Ball, Mauricio Reginato

Kimmel Cancer Center Faculty Papers

The growth of breast tumors is driven and controlled by a subpopulation of cancer cells resembling adult stem cells, which are called cancer stem-like cells (CSCs). In breast cancer, the function and maintenance of CSCs are influenced by protein O-GlcNAcylation and the enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, the mechanism of CSCs regulation by OGT and O-GlcNAc cycling in breast cancer is still unclear. Analysis of the proteome and O-GlcNAcome, revealed GATAD2B, a component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, as a substrate regulated by OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression …

Reconstitution Of Mirna-205 In Docetaxel Resistant Prostate Cancer Cells: A Nanotherapeutic Approach, Neeraj Chauhan, Eswara Naga Hanuma Kumar Ghali, Rahul Tiwari, Iris Enriquez, Rajasekhar Baru, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Prostate cancer (PrCa) is the second most diagnosed cancer and cause of death in men globally. Docetaxel (Dtxl) based first line chemotherapy is the main available therapeutic choice for PrCa patients. However, most (almost all) patients develop resistance to Dtxl treatment, making it difficult to treat such patients with no effective adjuvant therapy. Although cabazitaxel may be used to treat these patients, it is associated with many severe side effects including low white blood cells and allergic reactions. Therefore, finding an alternative strategy to reduce Dtxl resistance is of high importance for treating PrCa. miR-205 is a widely studied …

Developing Ship On-Chip Strategy Of Transporting Theranostic Radionuclides For Rapid And Efficient Radiopharmaceutical Production, Mai Lin, Robert Ta, Mark Mc Veigh, Joseph Lapka, Don Nolting, Leon Marcel Bellan, William Charlton, H. Charles Manning

Research Symposium

Introduction: Radiopharmaceuticals play a critical role in cancer diagnosis, staging, and therapy. Recent successes in radiotheranostics (which utilize targeted radiopharmaceutical pairs for both diagnosis and therapy) have led to improved outcomes in challenging clinical settings, such as neuroendocrine tumors and prostate cancer. Despite the tremendous potential, development of new radiopharmaceutical agents and widespread distribution is hampered by the extreme costs associated with production and delivery. Most hospitals require a substantial investment in facility and operational equipment for radiosynthesis that in turn limits the development of radiopharmaceuticals and their impact on precision medicine. Herein, we describe a simple and inexpensive microfluidic …

Roles Of Mir-223 In Platelet Function And High On-Treatment Platelet Reactivity: A Brief Report And Review, Shayan Askari, Lawrence E. Goldfinger

Cardeza Foundation for Hematologic Research

BACKGROUND: Platelets are highly enriched in microRNAs (miRNAs), which are genomically encoded 19-25 nucleotide non-coding RNAs that target complementary mRNAs through total or near-total base pairing. MiR-223 is among the most abundant miRNAs in human and murine platelets, but despite ongoing investigations in recent years, miR-223 roles in platelet physiology and its putative roles in high on-treatment platelet reactivity (HTPR) remain controversial, as studies showed varying findings.

OBJECTIVES: In the current hybrid review/report, we aim to compare studies that investigated miR-223 in platelet function and HTPR. Additionally, we briefly report our own findings on murine miR-223-deficient platelets.

METHODS: We have …

The Role Of The Female Reproductive Cycle In Social Communication And Relevance To Mental Health, Julissa Amaro Castillo, Fernando Dominguez, Ariana Hinojosa, Giselle Padilla, Mario Gil

Research Symposium

The female reproductive cycle is characterized by fluctuating hormones, including estrogens and progesterone, that are involved in reproductive health; however, they have also been linked to disorders like Premenstrual syndrome (PMS), Premenstrual Dysphoric Disorder (PMDD), mood swings, depression and others. The goal of this study is to use the Syrian hamster (Mesocricetus auratus) as an animal model to examine the influence of the reproductive cycle and hormones on behavior. Scent-marking activity known as flank marking is exhibited by territorial or sociable animals. In essence, animals mark their territory or convey information such as reproductive status by rubbing their flanks or …

Effects Of Arginine-Vasopressin In The Brain On Cardiovascular Function In A Psychosocial Stress Animal Model, Esmeralda Lopez-Garcia, Ariana V. Hinojosa, Esperanza I. Alaniz, Fernando Dominguez, Giselle Padilla, Mario Gil

Research Symposium

Background: Psychosocial stress impacts cardiovascular health, increasing the risk of events like myocardial infarction (MI), stress cardiomyopathy, and neuropsychiatric disorders, including Major Depressive Disorder (MDD) and Anxiety. However, our understanding of the biological mechanisms that connect psychosocial stress with negative cardiovascular and psychological outcomes remains incomplete. Arginine-vasopressin (AVP) is linked to both mental and physical health by regulating social behavior, blood pressure, and anxiety-related behaviors. This study investigates the potential cardioprotective effects of the neuropeptide AVP, in an effort to generate evidence that it may strengthen heart function and lessen the severity of adverse cardiovascular events caused by stress, brain …

Exploring The Effects Of Serotonin And Ssris On The Neurological, Behavioral, And Cardiovascular Systems Under Induced Stress –Using The Animal Model Of The Syrian Hamster, Ariana V. Hinojosa, Esperanza I. Alaniz, Esmeralda Lopez-Garcia, Giselle Padilla, Fernando Dominquez, Mario Gil

Research Symposium

Background: Serotonin is a neurotransmitter that has been found to have a wide range of effects on not just the neuropsychological processes but has also been found to exert effects outside the central nervous system (CNS); regulating numerous biological processes, such as metabolism, gastrointestinal system, reproductive function, and even the cardiovascular system. However, there is still a limited understanding of how serotonin affects all these systems due to its complexity and ability to regulate homeostasis. This project aims to create a stronger foundation of knowledge about serotonin and its influence on the interaction between the CNS, behavior, and cardiac function …

Detection Of Alteration In Carotid Artery Volumetry Using Standard-Of-Care Computed Tomography Surveillance Scans Following Unilateral Radiation Therapy For Early-Stage Tonsillar Squamous Cell Carcinoma Survivors: A Cross-Sectional Internally-Matched Carotid Isodose Analysis, Efstratios Koutroumpakis, Mohamed A Naser, Abdallah Sherif Radwan Mohamed, Salman A Eraj, Andrea Jarre, Jay C Shiao, Mona Kamal, Subha Perni, Jack P Phan, William H Morrison, Steven J Frank, G Brandon Gunn, Adam S Garden, Anita Deswal, Jun-Ichi Abe, David I Rosenthal, Elie Mouhayar, Clifton D Fuller

Faculty, Staff and Student Publications

Aim: This study leveraged standard-of-care CT scans of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer to detect volumetric changes in the carotid arteries, and determine whether there is a dose-response relationship.

Methods: Disease-free cancer survivors (>3 months since therapy and age > 18 years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded. Isodose lines from treatment plans were projected onto both scans, facilitating the delineation of carotid artery …

Investigating The Relationship Between The Circadian Clock, Age, And Lifestyle, Samuel Park, Amaka Eziakonwa, Amega Nguyen, Madison Payne, Erich Stahmer, Alexis Salinas, Payson Broome, Angel Oliver, Christian Mccormick, Jasmyn Brown, Julie A. Zacharias-Simpson, Jutta Ward, Deborah Bell-Pedersen

Annual Research Symposium

This poster presentation aims to understand how circadian clock strength and phase are affected by age and lifestyle. By analyzing changes in physiological rhythms, the study seeks to develop strategies for promoting healthy aging by optimizing circadian function.

Tracking The Effects Of Time Zone Shift On An Individual’S Circadian Rhythm, Amaka Eziakonwa, Erich Stahmer, Amega Nguyen, Samuel Park, Madison Payne, Alexis Salinas, Deborah Bell-Pedersen, Julie A. Zacharias-Simpson

Annual Research Symposium

This poster presentation aims to understand how a rapid time-zone change can affect an individual’s circadian rhythms. By quantifying changes in physiological rhythms, the study seeks to develop targeted therapeutic interventions to mitigate the negative effects of jetlag.

Can We Eliminate The Negative Consequences Of Circadian Desynchronization Caused By Night Shift Work By Using A Light Therapy Lamp To Simulate A Sunset?, Amega Nguyen, Madison Payne, Amaka Eziakonwa, Erich Stahmer, Alexis Salinas, Samuel Park, Julie A. Zacharias-Simpson, Deborah Bell-Pedersen

Annual Research Symposium

This poster aims to understand the relationship between desynchronosis of circadian rhythms and night-shift work and how light therapy can mitigate some of the issues of desynchronosis. This study seeks to develop therapies for disrupted circadian rhythms from night-ship works.

Transcranial Magnetic Stimulation As A Treatment Modality For Functional Bowel Disorder And Irritable Bowel Syndrome And Possible Correlations With The Gut-Brain Axis: A Review, Lauren Draper, Devin Pfister, Ethan Zaugg

Annual Research Symposium

Functional Bowel Disorders (FBD), including Irritable Bowel Syndrome (IBS), are highly prevalent gastrointestinal conditions classified as Disorders of Gut-Brain Interactions (DGBIs) under the Rome IV criteria. These conditions, marked by abdominal pain, altered bowel habits, and significant psychological comorbidities, present substantial challenges in both diagnosis and treatment. Conventional therapies primarily target gut-centric mechanisms but often yield limited efficacy, underscoring the need for approaches that account for the complex interplay of the gut-brain axis in DGBI pathophysiology.

Characteristics And Outcomes Of Adults Hospitalized With Respiratory Syncytial Virus, Brian S. Shaw, Cara Slaton, Ian P. Murphy, Michael Mcalister, Daniel Egan, Kwabena Ayesu

The University of Louisville Journal of Respiratory Infections

Background: Respiratory syncytial virus (RSV) is a negative sense single-stranded RNA virus (ssRNA) that primarily causes respiratory infections in both children and older adults. We examined clinical characteristics and outcomes of hospitalized adult patients who tested positive for RSV.

Methods: This was a multicenter, retrospective, descriptive study that examined adult patients admitted with a positive RSV test over two years across eight hospitals in Orlando, Florida.

Results: A total of 120 patients were included, of which 88 (73%) were 60 years old and older. Overall, patients with RSV infection were caucasian (62%) with a median age of 70 years and …

Notch3 Deletion Regulates Hiv-1 Gene Expression And Systemic Inflammation To Ameliorate Chronic Kidney Disease, Mackenzie Thornton, Nicole Sommer, Mercedes Mcgonigle, Anil Kumar Ram, Sireesha Yerrathota, Henrietta Ehirim, Aakriti Chaturvedi, Johnny Dinh Phan, Anubhav Chakraborty, V. Praveen Chakravarthi, Sumedha Gunewardena, Mudit Tyagi, Jaya Talreja, Tao Wang, Pravin Singhal, Pamela V. Tran, Timothy A. Fields, Patricio E. Ray, Navneet K. Dhillon, Madhulika Sharma

Center for Translational Medicine Faculty Papers

Anti-retroviral therapy (ART) has decreased human immunodeficiency virus (HIV)-1-associated morbidity. However, despite ART, immune cells remain latently infected, leading to chronic inflammation and HIV-1-associated comorbidities. New strategies are needed to target viral proteins and inflammation. We found activation of Notch3 in renal cells of the HIV-1 transgenic mouse model (HIV-Tg26) and in patients with HIV-associated nephropathy. We hypothesized that targeting NOTCH3 activation constitutes an effective therapy for HIV-related chronic kidney disease. We generated HIV-Tg26 mice with Notch3 knocked out (Tg-N3KO). Compared to HIV-Tg26 mice at 3 months, Tg-N3KO mice showed a marked reduction in renal injury, skin lesions and mortality …

Pull Or Play? The Interpretation Of A Novel, Ai-Powered On-Field Decision Support Tool., Lynne Becker, Dafne Badilla, Osho Yonzon, Xiaoyu Wu, Roland Rocafort, Erik Viogan Phd, Devansh Manocha

Journal for Sports Neuroscience

The document titled "Pull or Play? The interpretation of a novel, AI-powered on-field decision support tool" explores the development and application of the Injury Impact Severity Score (IISS)™ for assessing traumatic brain injuries (TBIs), particularly in sports settings. It addresses the limitations of current assessment tools like the Glasgow Coma Scale (GCS) and proposes a more objective approach using patient-reported data and machine learning algorithms.

Key points include:

• Background: TBIs are a significant health concern with under-reported cases and a lack of effective research. Current assessment tools like the GCS have limitations in accuracy and speed, especially in dynamic …

Application Of The Theory Of Planned Behavior In Concussion Disclosure: A Systematic Review, Michelle L. Weber Rawlins, R. Curtis Bay, Tamara Valovich Mcleod

Internet Journal of Allied Health Sciences and Practice

Purpose: Many athletes do not seek care for a suspected concussion for a number of reasons. Failing to do so can lead to persisting symptoms, longer recovery, or secondary injury. The Theory of Planned Behavior (TPB), along with knowledge of concussion, has been used to examine concussion care seeking. It is theorized that TPB components including attitudes, subjective norms, and self-efficacy are associated with one’s intention to perform a health-related behavior, and their actual behavior. Many studies have used the TPB in an attempt to predict concussion disclosure, with mixed results. The purpose of this systematic review was to determine …

Perinuclear Organelle Trauma At The Nexus Of Cardiomyopathy Pathogenesis Arising From Loss Of Function Lmna Mutation, Jason C. Choi

Center for Translational Medicine Faculty Papers

Over the past 25 years, nuclear envelope (NE) perturbations have been reported in various experimental models with mutations in the LMNA gene. Although the hypothesis that NE perturbations from LMNA mutations are a fundamental feature of striated muscle damage has garnered wide acceptance, the molecular sequalae provoked by the NE damage and how they underlie disease pathogenesis such as cardiomyopathy (LMNA cardiomyopathy) remain poorly understood. We recently shed light on one such consequence, by employing a cardiomyocyte-specific Lmna deletion in vivo in the adult heart. We observed extensive NE perturbations prior to cardiac function deterioration with collateral damage in the …

Editorial: Unveiling The Next Generation Of Cancer Immunity & Immunotherapy, Mohanraj Sadasivam, Nethaji Muniraj, Chellappagounder Thangavel

Center for Translational Medicine Faculty Papers

No abstract provided.

Poner En Práctica Las Regulaciones Federales: Habilitando A Los Pacientes Dominio Limitado Del Inglés, Caitlyn Gailey

World Languages and Cultures Senior Capstones

This paper examines the gaps in the U.S. healthcare system that affect the Hispanic community, focusing on language barriers and cultural competence. It highlights the challenges faced by Limited English Proficiency (LEP) patients, who may struggle with medical terminology, leading to misdiagnosis and improper treatment. The paper advocates for culturally sensitive language services, including qualified interpreters, translated documents and signage in order to improve communication, patient satisfaction, and reduce medical errors. It calls for systemic changes to ensure equitable care for all patients, regardless of language or cultural background.

El Uso De Las Prácticas Curativas No Occidentales En Lugar De Y Dentro De La Cultura Biomédica, Lynda Gulledge

World Languages and Cultures Senior Capstones

This paper explores the difficulties that the Hispanic community faces when accessing healthcare in the United States, which emphasizes the use of biomedical culture. Topics such as cultural and linguistic barriers, past and present healthcare policies, and the use of non-Western medical practices are examined. Furthermore, this paper explores the history and use of curanderismo as an accessible and culturally appropriate form of healthcare. Lastly, the integration and acknowledgement of curanderismo in biomedical culture is explored and encouraged in order to create a more holistic healthcare experience for the Hispanic community.