Medicine and Health Sciences Commons^™

Estimating The Number Of Polygenic Diseases Among Six Mutually Exclusive Entities Of Non-Tumors And Cancer, C I Edvard Smith, Jan A Burger, Rula Zain

Faculty, Staff and Student Publications

In the era of precision medicine with increasing amounts of sequenced cancer and non-cancer genomes of different ancestries, we here enumerate the resulting polygenic disease entities. Based on the cell number status, we first identified six fundamental types of polygenic illnesses, five of which are non-cancerous. Like complex, non-tumor disorders, neoplasms normally carry alterations in multiple genes, including in 'Drivers' and 'Passengers'. However, tumors also lack certain genetic alterations/epigenetic changes, recently named 'Goners', which are toxic for the neoplasm and potentially constitute therapeutic targets. Drivers are considered essential for malignant transformation, whereas environmental influences vary considerably among both types of …

Probabilistic Presurgical Language Fmri Atlas Of Patients With Brain Tumors, Jian Ming Teo, Vinodh A Kumar, Jina Lee, Rami W Eldaya, Ping Hou, Mu-Lan Jen, Kyle R Noll, Peng Wei, Sherise D Ferguson, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background and purpose: Patients with brain tumors have high intersubject variation in putative language regions, which may limit the utility of straightforward application of healthy subject brain atlases in clinical scenarios. The purpose of this study was to develop a probabilistic functional brain atlas that consolidates language functional activations of sentence completion and Silent Word Generation language paradigms using a large sample of patients with brain tumors.

Materials and methods: The atlas was developed using retrospectively collected fMRI data from patients with brain tumors who underwent their first standard-of-care presurgical language fMRI scan at our institution between July 18, 2015, …

Comparing Fermented Food And Vitamin E On Exercise-Mediated Nrf2/Are Activation In Middle-Aged/ Elderly: A Randomized, Double-Blind Clinical Study, Joseph Cervi, Reza Rastmanesh, Amir Moghadam-Ahmadi, Antonio Ayala, Cristiana Aperio, Aldo Lorenzetti, Maki Osato, Francesco Marotta, Antonio Nardin, Fang He

Department of Neuroscience Faculty Papers

Background: There is a compelling need to emphasize the importance of deepening the rationale behind functional foods research in molecular biology. Indeed, establishing stringent criteria to evaluate functional food interventions in disease prevention and as adjunctive therapeutic strategies offers significant opportunities for health promotion. Objective: This study investigated the effects of fermented papaya preparation (FPP®) and vitamin E on gene expression in middle-aged/elderly individuals, leveraging FPP’s established antioxidant and immune-regulatory benefits. Methods: Graded Exercise Walking Test was administered twice weekly for 6 months. Total Antioxidant capacity (TAC) and gene expression (Nrf2, NQO1, HO-1) in PBMC were measured monthly. Results: Throughout …

Automatically Extracting Social Determinants Of Health For Suicide: A Narrative Literature Review, Annika M Schoene, Suzanne Garverich, Iman Ibrahim, Sia Shah, Benjamin Irving, Clifford C Dacso

Faculty, Staff and Students Publications

Suicide is a complex phenomenon that is often not preceded by a diagnosed mental health condition, therefore making it difficult to study and mitigate. Artificial Intelligence has increasingly been used to better understand Social Determinants of Health factors that influence suicide outcomes. In this review we find that many studies use limited SDoH information and minority groups are often underrepresented, thereby omitting important factors that could influence risk of suicide.

Skn-1 Activation During Infection Of Caenorhabditis Elegans Requires Cdc-48 And Endoplasmic Reticulum Proteostasis, Carolaing Gabaldón, Ozgur Karakuzu, Danielle A Garsin

Faculty, Staff and Student Publications

During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 …

Multi-Omic Human Pancreatic Islet Endoplasmic Reticulum And Cytokine Stress Response Mapping Provides Type 2 Diabetes Genetic Insights., Eishani K Sokolowski, Romy Kursawe, Vijay Selvam, Redwan M Bhuiyan, Asa Thibodeau, Chi Zhao, Cassandra N Spracklen, Duygu Ucar, Michael L. Stitzel

Faculty Research 2024

Endoplasmic reticulum (ER) and inflammatory stress responses contribute to islet dysfunction in type 2 diabetes (T2D). Comprehensive genomic understanding of these human islet stress responses and whether T2D-associated genetic variants modulate them is lacking. Here, comparative transcriptome and epigenome analyses of human islets exposed ex vivo to these stressors revealed 30% of expressed genes and 14% of islet cis-regulatory elements (CREs) as stress responsive, modulated largely in an ER- or cytokine-specific fashion. T2D variants overlapped 86 stress-responsive CREs, including 21 induced by ER stress. We linked the rs6917676-T T2D risk allele to increased islet ER-stress-responsive CRE accessibility and allele-specific β …

Activation Of A Gpcr, Orl1 Receptor: A Novel Therapy To Prevent Heart Failure Progression, Saliha S Pathan, Aarthi Pugazenthi, Beverly R E A Dixon, Theodore G Wensel, Todd K Rosengart, Megumi Mathison

Faculty, Staff and Students Publications

The number of ischemic heart failure (HF) patients is growing dramatically worldwide. However, there are at present no preventive treatments for HF. Our previous study showed that Gata4 overexpression improved cardiac function after myocardial infarction in rat hearts. We also found that Gata4 overexpression significantly increased the expression of a Pnoc gene, an endogenous ligand for the cell membrane receptor ORL1. We hypothesized that the activation of the ORL1 receptor would suppress HF in a rat ischemic heart model. Adult Sprague Dawley rats (8 weeks old, six males and six females) underwent left anterior descending coronary artery ligation. Three weeks …

Gene Discovery From Microbial Gene Libraries I: Protection Against Reactive Oxygen Species-Driven Dna Damage, John C Taylor, Carmen Gu Liu, James D Chang, Brianna E Thompson, Anthony W Maresso

Faculty, Staff and Students Publications

Reactive oxygen species (ROS) pose a lethal risk for all life forms by causing damage to cell processes, genome-wide DNA damage-driving mutation, replicative instability, and death. Thus, the development of mechanisms to resist or repair ROS-induced DNA damage is critical for the reliable replication of nucleic acids. DNA repair and protection mechanisms have been discovered in all forms of life. However, the vast array of microbes that may harbor novel repair or protection mechanisms, especially bacterial viruses, have not been adequately assessed. Here, we screened a microbial gene library composed primarily of phage open reading frames (ORFs) to uncover elements …

Gpr56: Gpcr As A Guardian Against Ferroptosis, Yuelong Yan, Li Zhuang, Boyi Gan

Faculty, Staff and Student Publications

Transmembrane receptor proteins are proficient in sensing external signals and initiating downstream pathways to control cell survival. Lin et al. demonstrated that GPR56, a G-protein-coupled receptor, can be activated by its agonist to suppress ferroptosis-a form of cell death-and effectively mitigate ferroptosis-associated liver damage.

Mitral Annular Disjunction In Heritable Thoracic Aortic Disease: Insights From The Montalcino Aortic Consortium, Kishan L Asokan, Jennifer R Landes, Wannes Renders, Laura Muiño Mosquera, Julie De Backer, David W Jantzen, Anji T Yetman, Gisela Teixido-Tura, Arturo Evangelista, Richmond Jeremy, Edward G Jones, Shaine Morris, Tam Doan, Maral Ouzonian, Alan Braverman, Guillaume Jondeau, Olivier Milleron, Dianna M Milewicz, Siddharth K Prakash

Faculty, Staff and Student Publications

Background: Mitral annular disjunction (MAD), posterior displacement of the mitral valve leaflet hinge point, predisposes to arrhythmias or sudden cardiac death. We evaluated the burden of MAD, mitral valve prolapse (MVP), and mitral regurgitation (MR) by heritable thoracic aortic disease gene in a cross-sectional analysis of 2014-2023 data in the Montalcino Aortic Consortium registry.

Methods and results: MAD was determined by direct measurement of echocardiographic images. MR and MVP were defined according to current clinical guidelines. Associations were evaluated using χ2 or Fisher exact tests. MR and MVP were enriched in Montalcino Aortic Consortium participants (672) with pathogenic variants (PV) …

White Matter Hyperintensities And Mild Tbi In Post-9/11 Veterans And Service Members, David F Tate, Erin D Bigler, Gerald E York, Mary R Newsome, Brian A Taylor, Andrew R Mayer, Mary Jo Pugh, Angela P Presson, Zhining Ou, Elizabeth S Hovenden, Josephine Dimanche, Tracy J Abildskov, Rajan Agarwal, Heather G Belanger, Aaron M Betts, Timothy Duncan, Blessen C Eapen, Carlos A Jaramillo, Michael Lennon, Jennifer E Nathan, Randall S Scheibel, Matthew B Spruiell, William C Walker, Elisabeth A Wilde

Faculty, Staff and Student Publications

Introduction: The neurobehavioral significance of white matter hyperintensities (WMHs) seen on magnetic resonance imaging after traumatic brain injury (TBI) remains unclear, especially in Veterans and Service Members with a history of mild TBI (mTBI). In this study, we investigate the relation between WMH, mTBI, age, and cognitive performance in a large multisite cohort from the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium.

Materials and methods: The neuroimaging and neurobehavioral assessments for 1,011 combat-exposed, post-9/11 Veterans and Service Members (age range 22-69 years), including those with a history of at least 1 mTBI (n = 813; median …

Nerve Injury Inhibits Oprd1 And Cnr1 Transcription Through Rest In Primary Sensory Neurons, Ashok Subedi, Asieh Etemad, Aadhya Tiwari, Yuying Huang, Biji Chatterjee, Samantha M Mcleod, Yungang Lu, Diangelo Gonzalez, Krishna Ghosh, Mario Sirito, Sanjay K Singh, Elisa Ruiz, Sandra L Grimm, Cristian Coarfa, Hui-Lin Pan, Sadhan Majumder

Faculty, Staff and Students Publications

The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception. In this study, we determined the role of REST in controlling their expression in the DRG induced by spared nerve injury (SNI). SNI induced chronic pain hypersensitivity in wild-type mice and was accompanied by increased levels of Rest transcript and …

11.04.2024 Orsp Connect, Liz Williamson

ORED Newsletter

Small Grant Program for Faculty

Mid-South REACH Product Dev Grant

NSF Virtual Grants Conference

Racial And Sociodemographic Disparities In The Use Of Targeted Therapies In Advanced Ovarian Cancer Patients With Medicare, Anne Knisely, Chi-Fang Wu, Alexa Kanbergs, Nuria Agusti, Kirsten A Jorgensen, Alexander Melamed, Sharon H Giordano, Jose Alejandro Rauh-Hain, Roni Nitecki Wilke

Faculty, Staff and Student Publications

Objective: To describe sociodemographic and racial disparities in receipt of poly ADP-ribose polymerase inhibitors (PARPi) and bevacizumab among insured patients with ovarian cancer.

Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify patients with advanced stage, high grade serous ovarian cancer diagnosed between 2010 and 2019. The primary outcome of interest was receipt of PARPi or bevacizumab at any time after diagnosis. χ2 tests were used to compare categorical variables. Factors independently associated with the receipt of PARPi and/or bevacizumab were identified using a multivariable logistic regression.

Results: The cohort included 6242 patients; 276 …

Obesity And Outcomes In Adoptive Cellular Therapy In Solid Tumors, Derrick L Tao, Mirella Nardo, Cheuk Hong Leung, Heather Y Lin, Lei Kang, Hung Le, Ecaterina E Dumbrava, David S Hong

Faculty, Staff and Student Publications

This cohort study investigates the association of obesity with adoptive cell therapy outcomes in patients with solid tumors.

Patient-Reported Convenience And Effectiveness Of Telehealth For Breast Cancer Management, Akshara Singareeka Raghavendra, Kristofer Jennings, Gil Guerra, Debu Tripathy, Meghan S Karuturi

Faculty, Staff and Student Publications

Background: Before the coronavirus disease 2019 (COVID-19) pandemic, telehealth was rarely used for breast cancer management at tertiary care centers. We sought to examine patient satisfaction, experiences, preferences, and perceived effectiveness and technical quality of telehealth visits in follow-up patients receiving routine outpatient care in the breast medical oncology practice at The University of Texas MD Anderson Cancer Center.

Methods: We administered a survey to 60 follow-up patients for a duration of 9 months (January 5, 2021 to October 27, 2021) who had at least one telehealth consultation during the COVID-19 pandemic, from April 10, 2020 to October 21, 2021. …

Fc-Enhanced Anti-Ctla-4, Anti-Pd-1, Doxorubicin, And Ultrasound-Mediated Blood-Brain Barrier Opening: A Novel Combinatorial Immunotherapy Regimen For Gliomas, Kwang-Soo Kim, Karl Habashy, Andrew Gould, Junfei Zhao, Hinda Najem, Christina Amidei, Ruth Saganty, Víctor A Arrieta, Crismita Dmello, Li Chen, Daniel Y Zhang, Brandyn Castro, Leah Billingham, Daniel Levey, Olivia Huber, Marilyn Marques, David A Savitsky, Benjamin M Morin, Miguel Muzzio, Michael Canney, Craig Horbinski, Peng Zhang, Jason Miska, Surya Padney, Bin Zhang, Raul Rabadan, Joanna J Phillips, Nicholas Butowski, Amy B Heimberger, Jian Hu, Roger Stupp, Dhan Chand, Catalina Lee-Chang, Adam M Sonabend

Faculty, Staff and Student Publications

Background: Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in "cold" and immunotherapy-refractory cancers.

Methods: We evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor-associated macrophages/microglia (TAMs).

Results: FcE-aCTLA-4 demonstrated high-affinity binding …

Thrombosis, Brain Metastasis Formation, And The Perivascular Metastatic Niche-Novel Insights From The Tumor Microvascular Circulation, Christopher Alvarez-Breckenridge, Priscilla K Brastianos, Daniel P Cahill

Faculty, Staff and Student Publications

No abstract provided.

The Emerging Field Of Viroimmunotherapy For Pediatric Brain Tumors, Marc Garcia-Moure, Virginia Laspidea, Sumit Gupta, Andrew G Gillard, Soumen Khatua, Akhila Parthasarathy, Jiasen He, Frederick F Lang, Juan Fueyo, Marta M Alonso, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Pediatric brain tumors are the most common solid tumors in children. Even to date, with the advances in multimodality therapeutic management, survival outcomes remain dismal in some types of tumors, such as pediatric-type diffuse high-grade gliomas or central nervous system embryonal tumors. Failure to understand the complex molecular heterogeneity and the elusive tumor and microenvironment interplay continues to undermine therapeutic efficacy. Developing a strategy that would improve survival for these fatal tumors remains unmet in pediatric neuro-oncology. Oncolytic viruses (OVs) are emerging as a feasible, safe, and promising therapy for brain tumors. The new paradigm in virotherapy implies that the …

Impa1-Derived Inositol Maintains Stemness In Castration-Resistant Prostate Cancer Via Impdh2 Activation, Che-Chia Hsu, Guihua Wang, Chien-Feng Li, Xian Zhang, Zhen Cai, Tingjin Chen, Bo-Syong Pan, Rajesh Kumar Manne, Gagan Deep, Haiwei Gu, Yuzhuo Wang, Danni Peng, Vasudevarao Penugurti, Xiaobo Zhou, Zhigang Xu, Zhongzhu Chen, Ming Chen, Andrew J Armstrong, Jiaoti Huang, Hong-Yu Li, Hui-Kuan Lin

Faculty, Staff and Student Publications

Acquisition of prostate cancer stem cells (PCSCs) manifested during androgen ablation therapy (ABT) contributes to castration-resistant prostate cancer (CRPC). However, little is known about the specific metabolites critically orchestrating this process. Here, we show that IMPA1-derived inositol enriched in PCSCs is a key metabolite crucially maintaining PCSCs for CRPC progression and ABT resistance. Notably, conditional Impa1 knockout in the prostate abrogates the pool and properties of PCSCs to orchestrate CRPC progression and prolong the survival of TRAMP mice. IMPA1-derived inositol serves as a cofactor that directly binds to and activates IMPDH2, which synthesizes guanylate nucleotides for maintaining PCSCs with ARlow/- …

Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy In High-Grade Epithelial Ovarian Cancer: A Lance Randomized Clinical Trial, J Alejandro Rauh-Hain, Alexander Melamed, René Pareja, Taymaa May, Abdulrahman Sinno, Leah Mcnally, Neil S Horowitz, Pierandrea De Iaco, Chad M Michener, Luc Van Lonkhuijzen, Maria D Iniesta, Ying Yuan, Pedro T Ramirez, Anna Fagotti

Faculty, Staff and Student Publications

Importance: Despite the absence of high-quality evidence of its safety and effectiveness, minimally invasive surgery (MIS) is increasingly used to treat advanced epithelial ovarian cancer (EOC).

Objective: To assess the feasibility of conducting a full-scale randomized clinical trial (RCT) designed to compare the efficacy of MIS vs laparotomy in patients with advanced-stage EOC and a complete or partial response to neoadjuvant chemotherapy (NACT).

Design, setting, and participants: This lead-in pilot phase of LANCE (Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy), an international, open-label, noninferiority RCT, opened to enrollment in September 2020 and enrolled the 100th eligible patient in February 2023. It was …

2024-25 Women In Science Conference Schedule (Pdf), Lynn University

Women in Science Conference

2024-25 Women in Environmental Science Conference Schedule (PDF)

Tak1 Blockade Plus Azacitidine Induces Apoptosis, Augments Cytarabine, And Ablates Clonogenicity In Mll-Af9+ Human Aml Cell Lines, Austin P. Runde, Cameron Lewis, Peter Breslin Sj, Jiwang Zhang

School of Medicine

Acute myeloid leukemia (AML) encompasses a diverse group of cancers that originate in the blood-forming tissues of the bone marrow [1]. Aside from the PML-RARA⁺ subtype, AML carries a 5-year survival rate of 28% for patients 20+ years of age. AML is the most common cancer of the hematopoietic system and is slightly more common in biological males; the average age at diagnosis is 68 years. Standard frontline treatment for AML is a two-phase regimen of intensive chemotherapy (CTx) employing daunorubicin and cytarabine; etoposide may also be added in select regimens. Despite 60-70% of patients achieving complete remission (CR), …

Protein Consumption And Risk Of Cvd Among Us Adults: The Multi-Ethnic Study Of Atherosclerosis (Mesa), Ji Yun Tark, Ruosha Li, Bing Yu, Alexis C Wood, Nikhil S Padhye, Marcia C De Oliveira Otto

Faculty, Staff and Students Publications

BACKGROUND: Although some randomized trials have reported beneficial effects of protein intake on cardiometabolic risk factors, evidence from prospective studies have not supported a strong link between protein intake and cardiovascular disease (CVD) risk. It is also unclear whether diversity in protein intake plays a role in CVD risk.

OBJECTIVE: We investigated prospective associations of (1) protein intake, overall and by food source and (2) diversity of protein sources with risk of CVD, coronary heart disease (CHD), and stroke.

METHODS: In a multi-ethnic cohort of 5879 U.S. adults (45-84 years), who were free of CVD at baseline, protein intake was …

Proceedings From The Fifth Annual For Society For Sports Neuroscience Conference, Neurosports Editorial Staff

Journal for Sports Neuroscience

Proceedings from the Fifth Annual for Society for Sports Neuroscience Conference

Mechanisms Of Extracellular Vesicle Uptake And Implications For The Design Of Cancer Therapeutics, Stephanie R Jackson Cullison, Joseph P Flemming, Kubra Karagoz, Peter J Wermuth, Mỹ G Mahoney

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as …

Impact Of Pathologist-Directed Comprehensive Genomic Profiling In Advanced Non-Small-Cell Lung Cancer In A Large Healthcare System, R Meng, Carlo Bifulco, Brian Piening, See Full List Of Authors In Comments

Articles, Abstracts, and Reports

No abstract provided.

2024 - The Fifth Annual Fall Symposium Of Student Scholars

Symposium of Student Scholars Program Books

The full program book from the Fall 2024 Symposium of Student Scholars, held in November 2024. Includes abstracts from the presentations and posters.

Viral Genome Delivery Across Bacterial Cell Surfaces, Stephano M. Iglesias, Fenglin Li, Federica Briani, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

In 1952, Hershey and Chase used bacteriophage T2 genome delivery inside Escherichia coli to demonstrate that DNA, not protein, is the genetic material. Over 70 years later, our understanding of bacteriophage structure has grown dramatically, mainly thanks to the cryogenic electron microscopy revolution. In stark contrast, phage genome delivery in prokaryotes remains poorly understood, mainly due to the inherent challenge of studying such a transient and complex process. Here, we review the current literature on viral genome delivery across bacterial cell surfaces. We focus on icosahedral bacterial viruses that we arbitrarily sort into three groups based on the presence and …

Genomic Landscape Of Fusions In Solid Tumors Detected By Dna And Rna Comprehensive Genomic Profiling At A Large Community Health System, A Dowdell, Carlo Bifulco, Brian Piening, See Full List Of Authors In Comments

Articles, Abstracts, and Reports

No abstract provided.