Genetic Phenomena Commons^™

Dimerization Of The 4ig Isoform Of B7-H3 In Tumor Cells Mediates Enhanced Proliferation And Tumorigenic Signaling, Margie N Sutton, Sarah E Glazer, Riccardo Muzzioli, Ping Yang, Seth T Gammon, David Piwnica-Worms

Faculty, Staff and Student Publications

B7-H3 (CD276) has two isoforms (2Ig and 4Ig), no confirmed cognate receptor, and physiological functions that remain elusive. While differentially expressed on many solid tumors correlating with poor survival, mechanisms of how B7-H3 signals in cis (tumor cell) versus in trans (immune cell co-regulator) to elicit pro-tumorigenic phenotypes remain poorly defined. Herein, we characterized a tumorigenic and signaling role for tumor cell-expressed 4Ig-B7-H3, the dominant human isoform, in gynecological cancers that could be abrogated upon CRISPR/Cas9 knockout of B7-H3; tumorigenesis was rescued upon re-expression of 4Ig-B7-H3. Size exclusion chromatography revealed dimerization states for the extracellular domains of both human 4Ig- …

Pancanqtlv20: A Comprehensive Resource For Expression Quantitative Trait Loci Across Human Cancers, Chengxuan Chen, Yuan Liu, Mei Luo, Jingwen Yang, Yamei Chen, Runhao Wang, Joseph Zhou, Yong Zang, Lixia Diao, Leng Han

Faculty, Staff and Student Publications

Expression quantitative trait locus (eQTL) analysis is a powerful tool used to investigate genetic variations in complex diseases, including cancer. We previously developed a comprehensive database, PancanQTL, to characterize cancer eQTLs using The Cancer Genome Atlas (TCGA) dataset, and linked eQTLs with patient survival and GWAS risk variants. Here, we present an updated version, PancanQTLv2.0 (https://hanlaboratory.com/PancanQTLv2/), with advancements in fine-mapping causal variants for eQTLs, updating eQTLs overlapping with GWAS linkage disequilibrium regions and identifying eQTLs associated with drug response and immune infiltration. Through fine-mapping analysis, we identified 58 747 fine-mapped eQTLs credible sets, providing mechanic insights of gene regulation in …

Contributions Of The Microbiome-Derived Metabolome For Risk Assessment And Prognostication Of Pancreatic Cancer, Ricardo A León-Letelier, Rongzhang Dou, Jody Vykoukal, Michele T Yip-Schneider, Anirban Maitra, Ehsan Irajizad, Ranran Wu, Jennifer B Dennison, Kim-An Do, Jianjun Zhang, C Max Schmidt, Samir Hanash, Johannes F Fahrmann

Faculty, Staff and Student Publications

Background: Increasing evidence implicates microbiome involvement in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Studies suggest that reflux of gut or oral microbiota can lead to colonization in the pancreas, resulting in dysbiosis that culminates in release of microbial toxins and metabolites that potentiate an inflammatory response and increase susceptibility to PDAC. Moreover, microbe-derived metabolites can exert direct effector functions on precursors and cancer cells, as well as other cell types, to either promote or attenuate tumor development and modulate treatment response.

Content: The occurrence of microbial metabolites in biofluids thereby enables risk assessment and prognostication of PDAC, …

Mir126-Targeted-Nanoparticles Combined With Pi3k/Akt Inhibitor As A New Strategy To Overcome Melanoma Resistance, Maria Beatrice Arasi, Gabriele De Luca, Laura Chronopoulou, Francesca Pedini, Eleonora Petrucci, Michela Flego, Annarita Stringaro, Marisa Colone, Luca Pasquini, Massimo Spada, Valentina Lulli, Maria Chiara Perrotta, George Adrian Calin, Cleofe Palocci, Mauro Biffoni, Federica Felicetti, Nadia Felli

Faculty, Staff and Student Publications

Metastatic melanoma poses significant challenges as a highly lethal disease. Despite the success of molecular targeting using BRAFV600E inhibitors (BRAFis) and immunotherapy, the emergence of early recurrence remains an issue and there is the need for novel therapeutic approaches. This study aimed at creating a targeted delivery system for the oncosuppressor microRNA 126 (miR126) and testing its effectiveness in combination with a phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT) inhibitor for treating metastatic melanoma resistant to BRAFis. To achieve this, we synthesized chitosan nanoparticles containing a chemically modified miR126 sequence. These nanoparticles were further functionalized with an antibody specific to …

Class Ii Hla-Drb4 Is A Predictive Biomarker For Survival Following Immunotherapy In Metastatic Non-Small Cell Lung Cancer, Cindy Y Jiang, Lili Zhao, Michael D Green, Shashidhar Ravishankar, Andrea M H Towlerton, Anthony J Scott, Malini Raghavan, Matthew F Cusick, Edus H Warren, Nithya Ramnath

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICI) are important treatment options for metastatic non-small cell lung cancer (mNSCLC). However, not all patients benefit from ICIs and can experience immune-related adverse events (irAEs). Limited understanding exists for germline determinants of ICI efficacy and toxicity, but Human Leukocyte Antigen (HLA) genes have emerged as a potential predictive biomarker. We performed HLA typing on 85 patients with mNSCLC, on ICI therapy and analyzed the impact of HLA Class II genotype on progression free survival (PFS), overall survival (OS), and irAEs. Most patients received pembrolizumab (83.5%). HLA-DRB4 genotype was seen in 34/85 (40%) and its presence correlated …

Integrated Multi-Omics Analyses Identify Anti-Viral Host Factors And Pathways Controlling Sars-Cov-2 Infection, Jiakai Hou, Yanjun Wei, Jing Zou, Roshni Jaffery, Long Sun, Shaoheng Liang, Ningbo Zheng, Ashley M Guerrero, Nicholas A Egan, Ritu Bohat, Si Chen, Caishang Zheng, Xiaobo Mao, S Stephen Yi, Ken Chen, Daniel J Mcgrail, Nidhi Sahni, Pei-Yong Shi, Yiwen Chen, Xuping Xie, Weiyi Peng

Faculty, Staff and Student Publications

Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-Seq, and host-virus proteins or protein/RNA interactome. This study uncovers many host factors that are currently underappreciated, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulate viral entry and/or replication. The cohesin complex is also identified as an anti-viral pathway, suggesting an important role of …

Serine Synthesis Via Reversed Shmt2 Activity Drives Glycine Depletion And Acetaminophen Hepatotoxicity In Masld, Alia Ghrayeb, Alexandra C Finney, Bella Agranovich, Daniel Peled, Sumit Kumar Anand, M Peyton Mckinney, Mahasen Sarji, Dongshan Yang, Natan Weissman, Shani Drucker, Sara Isabel Fernandes, Jonatan Fernández-García, Kyle Mahan, Zaid Abassi, Lin Tan, Philip L Lorenzi, James Traylor, Jifeng Zhang, Ifat Abramovich, Y Eugene Chen, Oren Rom, Inbal Mor, Eyal Gottlieb

Faculty, Staff and Student Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of the global population. Understanding the metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative …

Unraveling The Intercellular Communication Disruption And Key Pathways In Alzheimer’S Disease: An Integrative Study Of Single-Nucleus Transcriptomes And Genetic Association, Andi Liu, Brisa S Fernandes, Citu Citu, Zhongming Zhao

Faculty, Staff and Student Publications

BACKGROUND: Recently, single-nucleus RNA-seq (snRNA-seq) analyses have revealed important cellular and functional features of Alzheimer's disease (AD), a prevalent neurodegenerative disease. However, our knowledge regarding intercellular communication mediated by dysregulated ligand-receptor (LR) interactions remains very limited in AD brains.

METHODS: We systematically assessed the intercellular communication networks by using a discovery snRNA-seq dataset comprising 69,499 nuclei from 48 human postmortem prefrontal cortex (PFC) samples. We replicated the findings using an independent snRNA-seq dataset of 56,440 nuclei from 18 PFC samples. By integrating genetic signals from AD genome-wide association studies (GWAS) summary statistics and whole genome sequencing (WGS) data, we prioritized …

In Vivo Scanning Laser Fundus And High-Resolution Oct Imaging Of Retinal Ganglion Cell Injury In A Non-Human Primate Model With An Activatable Fluorescent-Labeled Tat Peptide Probe, Xudong Qiu, Seth T Gammon, Carol Rasmussen, Federica Pisaneschi, Charlene B Y Kim, James Ver Hoeve, Steven W Millward, Edward M Barnett, T Michael Nork, Paul L Kaufman, David Piwnica-Worms

Faculty, Staff and Student Publications

The optical imaging agent TcapQ488 has enabled imaging of retinal ganglion cell (RGC) injury in vivo in rodents and has potential as an effective diagnostic probe for early detection and intervention monitoring in glaucoma patients. In the present study, we investigated TcapQ488 in non-human primates (NHPs) to identify labeling efficacy and early signals of injured RGC, to determine species-dependent changes in RGC probe uptake and clearance, and to determine dose-limiting toxicities. Doses of 3, 6, and 12 nmol of TcapQ488 were delivered intravitreally to normal healthy NHP eyes and eyes that had undergone hemiretinal endodiathermy axotomy (HEA) in the inferior …

Facilitating Clinical Information Extraction With Synthetic Data And Ontology Using Large Language Models, Yan Hu, Huan He, Qingyu Chen, Xiaoqian Jiang, Kirk Roberts, Hua Xu

Faculty, Staff and Student Publications

The rapid growth of unstructured clinical text in electronic health records necessitates robust information extraction systems, yet their development is hindered by the scarcity of high-quality annotated data. This study explores the potential of large language models to generate synthetic data for clinical named entity recognition and examines its impact on model performance. We propose a novel framework that integrates self-verified synthetic data generation with domain-specific semantic mapping using SNOMED-CT. By leveraging GPT-4o-mini for synthetic data creation and refining its quality through iterative verification and anomaly detection, we systematically evaluate the influence of synthetic data quality and quantity on fine-tuning …

Design And Implementation Of Multicenter Pediatric And Congenital Studies With Cardiovascular Magnetic Resonance: Big Data In Smaller Bodies, Michael P Dilorenzo, Simon Lee, Rahul H Rathod, Francesca Raimondi, Kanwal M Farooqi, Supriya S Jain, Margaret M Samyn, Tiffanie R Johnson, Laura J Olivieri, Mark A Fogel, Wyman W Lai, Pierangelo Renella, Andrew J Powell, Sujatha Buddhe, Caitlin Stafford, Jason N Johnson, Willem A Helbing, Kuberan Pushparajah, Inga Voges, Vivek Muthurangu, Kimberley G Miles, Gerald Greil, Colin J Mcmahon, Timothy C Slesnick, Brian M Fonseca, Shaine A Morris, Jonathan H Soslow, Lars Grosse-Wortmann, Rebecca S Beroukhim, Heynric B Grotenhuis

Faculty, Staff and Student Publications

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, …

Developing Medical Genetics In A Low-Income Country: Unveiling The Journey Of The Pakistani Society Of Medical Genetics And Genomics (Psmg), Aisha Furqan, Syed A Ahmed, Rizwan Naeem, Myla Ashfaq

Faculty, Staff and Student Publications

No abstract provided.

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 …

Pan-Cancer Genomic Characterization Of Human Papillomavirus Associated Tumors, Jeremiah Ray Holt

Theses and Dissertations (ETD)

Infection with high-risk human papillomavirus (HPV) accounts for nearly all cervical cancers (CESC), a subset of other anogenital squamous cancers, and increasing rates of head and neck squamous cell carcinomas (HNSC), with each cancer type having heterogenous outcomes due to a general lack of personalized care. Large scale genomic analyses have catalogued the somatic alterations occurring frequently among squamous tumor types including HNSC and CESC, but few studies have incorporated a thorough analysis of HPV genomics. High-risk HPVs are double-stranded DNA (dsDNA) viruses capable of integrating their genomes into host chromosomes, a phenomenon known to promote HPV-associated cancer formation. HPV …

Patterns Of Failure For Recurrent Head And Neck Squamous Cell Carcinoma Treated With Salvage Surgery And Postoperative Imrt Reirradiation, Abdallah S R Mohamed, Geoffrey V Martin, Sweet Ping Ng, Vinita Takiar, Beth M Beadle, Mark Zafereo, Adam S Garden, Steven J Frank, C David Fuller, G Brandon Gunn, William H Morrison, David I Rosenthal, Jay Reddy, Amy Moreno, Anna Lee, Jack Phan

Faculty, Staff and Student Publications

PURPOSE/OBJECTIVES: The purpose of this study was to evaluate patterns of locoregional recurrence (LRR) after surgical salvage and adjuvant reirradiation with IMRT for recurrent head and neck squamous cell cancer (HNSCC).

MATERIALS/METHODS: Patterns of LRR for 61 patients treated consecutively between 2003 and 2014 who received post-operative IMRT reirradiation to ≥ 60 Gy for recurrent HNSCC were determined by 2 methods: 1) physician classification via visual comparison of post-radiotherapy imaging to reirradiation plans; and 2) using deformable image registration (DIR). Those without evaluable CT planning image data were excluded. All recurrences were verified by biopsy or radiological progression. Failures were …

The Feasibility Of Health Professional Student Delivered Social Visits For Stroke Survivors With Loneliness, Jason Burnett, Jordan Broussard, Bronson Ciavarra, Louisa Smitherman, Mary Li, Emma Thames, Sharon Zachariah, Grace Kim, Rachel Pijnnaken, Hannah Zeller, John Halphen, Sean I Savitz, Namkee Choi, Jennifer E S Beauchamp

Faculty, Staff and Student Publications

Objectives: To examine the feasibility of a social phone call program to address social isolation and loneliness in stroke survivors.

Materials and methods: We paired 14 lonely community-living stroke survivors with 14 health professional students for 6-weekly unstructured social phone calls. Feasibility data and measures of social isolation, loneliness and other psychosocial metrics were collected pre- and post-intervention. Students journaled following each unstructured call to capture the informal conversation and their sentiments.

Results: Sixty-two percent of the targeted sample was interested. Fourteen eligible and interested participants were enrolled. The 13 (93%) participants completing all calls and surveys were an average …

Fgf5, Evelyn A Carrion, Malcolm M Moses, Richard R Behringer

Faculty, Staff and Student Publications

FGF5 functions as a negative regulator of the hair cycle in mammals. It is expressed in the outer root sheath of hair follicles during the late anagen phase of the hair cycle. It functions as a signaling molecule, mediating the transition of the anagen growth phase to catagen regression phase of the hair cycle. Spontaneous and engineered FGF5 mutations in mammalian animal models result in long hair phenotypes. In humans, inherited FGF5 mutations result in trichomegaly (long eyelashes). Knockdown of fgf5 in zebrafish embryos results in inner ear alterations. Alterations in FGF5 expression are also associated with various human pathologies.

Sudden Unexpected Intrapartum Death And Left Ventricular Noncompaction Involving The Right Ventricle, Giulia Ottaviani, Tobia Tomasello, Francesca Boggio, Letterio Runza, Alessandro Del Gobbo, L Maximilian Buja

Faculty, Staff and Student Publications

Left ventricular noncompaction (LVNC), involving mainly the right ventricle, is a rare form of congenital heart disorder characterized by a developmental arrest in myocardial compaction, resulting in a spongy appearance of the myocardium, mainly of the right ventricle, rarely detected in fetuses. We report the case of a female fetus with a gestational age of 41+4 weeks who came to our attention for intrapartum sudden unexpected death, resulting in stillbirth. The ventricular walls, particularly the right ventricular wall, appeared thick, hypertrabeculated and spongy, leading to the diagnosis of LVNC involving mainly the right ventricle. The atrioventricular node and His bundle …

Chronic Lymphocytic Leukemia: Disease Biology, Stefan Koehrer, Jan A Burger

Faculty, Staff and Student Publications

Background: B-cell receptor (BCR) signaling is crucial for normal B-cell development and adaptive immunity. In chronic lymphocytic leukemia (CLL), the malignant B cells display many features of normal mature B lymphocytes, including the expression of functional B-cell receptors (BCRs). Cross talk between CLL cells and the microenvironment in secondary lymphatic organs results in BCR signaling and BCR-driven proliferation of the CLL cells. This critical pathomechanism can be targeted by blocking BCR-related kinases (BTK, PI3K, spleen tyrosine kinase) using small-molecule inhibitors. Among these targets, Bruton tyrosine kinase (BTK) inhibitors have the highest therapeutic efficacy; they effectively block leukemia cell proliferation and …

Enhancing Associative Learning In Rats With A Computationally Designed Training Protocol, Xu O Zhang, Yili Zhang, Claire E Cho, Douglas S Engelke, Paul Smolen, John H Byrne, Fabricio H Do-Monte

Faculty, Staff and Student Publications

Background: Learning requires the activation of protein kinases with distinct temporal dynamics. In Aplysia, nonassociative learning can be enhanced by a computationally designed learning protocol with intertrial intervals (ITIs) that maximize the interaction between fast-activated PKA (protein kinase A) and slow-activated ERK (extracellular signal-regulated kinase). Whether a similar strategy can enhance associative learning in mammals is unknown.

Methods: We simulated 1000 training protocols with varying ITIs to predict an optimal protocol based on empirical data for PKA and ERK dynamics in rat hippocampus. Adult male rats received the optimal protocol or control protocols in auditory fear conditioning and fear …

Author Correction: Enhanced Cd19 Activity In B Cells Contributes To Immunodeficiency In Mice Deficient In The Icf Syndrome Gene Zbtb24, Zhengzhou Ying, Swanand Hardikar, Joshua B Plummer, Tewfik Hamidi, Bin Liu, Yueping Chen, Jianjun Shen, Yunxiang Mu, Kevin M Mcbride, Taiping Chen

Faculty, Staff and Student Publications

No abstract provided.

Risk Stratification And Prediction Of Severity Of Covid-19 Infection In Patients With Preexisting Cardiovascular Disease, Stanislava Matejin, Igor D Gregoric, Rajko Radovancevic, Slobodan Paessler, Vladimir Perovic

Faculty, Staff and Student Publications

Introduction: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a highly contagious viral disease. Cardiovascular diseases and heart failure elevate the risk of mechanical ventilation and fatal outcomes among COVID-19 patients, while COVID-19 itself increases the likelihood of adverse cardiovascular outcomes.

Methods: We collected blood samples and clinical data from hospitalized cardiovascular patients with and without proven COVID-19 infection in the time period before the vaccine became available. Statistical correlation analysis and machine learning were used to evaluate and identify individual parameters that could predict the risk of needing mechanical ventilation and patient survival.

Results: Our results confirmed that COVID-19 …

Clinical Characteristics And Outcomes Of Adult Alveolar Rhabdomyosarcoma Patients On First-Line Systemic Therapies: A Single-Institution Cohort, Michael S Nakazawa, J Andrew Livingston, Maria A Zarzour, Andrew J Bishop, Ravin Ratan, Joseph A Ludwig, Dejka M Araujo, Neeta Somaiah, Vinod Ravi, Elise F Nassif, Christina L Roland, Alexander J Lazar, B Ashleigh Guadagnolo, Douglas J Harrison, Robert S Benjamin, Shreyaskumar R Patel, Anthony P Conley

Faculty, Staff and Student Publications

Background: Rhabdomyosarcomas are the most common soft tissue sarcoma in children, and pediatric alveolar rhabdomyosarcoma (ARMS) prognosis has improved based on cooperative studies. However, in adults, ARMS is significantly rarer, has poorer outcomes, and currently lacks optimal treatment strategies. Objective: This study aimed to evaluate the clinical outcome of an adult ARMS population with different front-line systemic chemotherapies and determine if any chemotherapy regimen is associated with improved survival. ]

Materials and methods: This is a retrospective study of histologically confirmed fusion-positive ARMS patients over 18 years of age, who were treated at MD Anderson Cancer Center (MDACC) from 2004 …

Bayesian Optimal Designs For Multi-Arm Multi-Stage Phase Ii Randomized Clinical Trials With Multiple Endpoints, Guillaume Mulier, Sylvie Chevret, Ruitao Lin, Lucie Biard

Faculty, Staff and Student Publications

There is a growing need to evaluate of multiple competing drugs in phase II trials where the number of patients is often limited, and simultaneous assessment of both efficacy and toxicity is crucial. To avoid the waste of research resources, it is indeed more efficient to screen multiple drugs at once in a platform phase II setting. We aim to adapt the Bayesian optimal phase II (BOP2) design to multi-arm trials for both uncontrolled and controlled settings. The binary efficacy and toxicity endpoints are modeled by a Dirichlet distribution as a vector of four outcomes. Posterior marginal distributions at each …

On The Relative Conservativeness Of Bayesian Logistic Regression Method In Oncology Dose-Finding Studies, Cheng-Han Yang, Guanghui Cheng, Ruitao Lin

Faculty, Staff and Student Publications

The Bayesian logistic regression method (BLRM) is a widely adopted and flexible design for finding the maximum tolerated dose in oncology phase I studies. However, the BLRM design has been criticized in the literature for being overly conservative due to the use of the overdose control rule. Recently, a discussion paper titled "Improving the performance of Bayesian logistic regression model with overall control in oncology dose-finding studies" in Statistics in Medicine has proposed an overall control rule to address the "excessive conservativeness" of the standard BLRM design. In this short communication, we discuss the relative conservativeness of the standard BLRM …

Systematic Review And Meta-Analysis Of Acupuncture For Modulation Of Immune And Inflammatory Markers In Cancer Patients, Wenli Liu, Baisong Zhong, Richard W Wagner, M Kay Garcia, Jennifer L Mcquade, Wen Huang, Yisheng Li, Graciela M Nogueras Gonzalez, Michael R Spano, Alessandro Cohen, Yimin Geng, Lorenzo Cohen

Faculty, Staff and Student Publications

Introduction: Inflammation is associated with tumor initiation, and existing tumors are associated with immune suppression locally and systemically. Cancer treatment is also associated with immune suppression. This review evaluates evidence related to the use of acupuncture for modulation of inflammation and the immune system in cancer patients.

Methods: Nine databases were searched for prospective, randomized, controlled trials evaluating the use of acupuncture for modulation of the immune system in cancer patients through March 2024. Only studies involving needle insertion into acupuncture points were included. No language limitations were applied. Studies were assessed for risk of bias (ROB) according to Cochrane …

Commitment Complex Splicing Factors In Cancers Of The Gastrointestinal Tract-An In Silico Study, Yun Zhang, Alexandria Carrasquillo Simko, Uzondu Okoro, Deja Jamese Sibert, Jin Hyung Moon, Bin Liu, Angabin Matin

Faculty, Staff and Student Publications

The initial step in pre-mRNA splicing involves formation of a spliceosome commitment complex (CC) or E-complex by factors that serve to bind and mark the exon-intron boundaries that will undergo splicing. The CC component U1 snRNP assembles at the 5'-splice site (ss), whereas SF1, U2AF2, and U2AF1 define the 3'-ss of the intron. A PRP40 protein bridges U1 snRNP with factors at the 3'-ss. To determine how defects in CC components impact cancers, we analyzed human gastrointestinal (GI) cancer patient tissue and clinical data from cBioPortal. cBioPortal datasets were analyzed for CC factor alterations and patient outcomes in GI cancers …

Pancreatic Cancer Action Network's Spark: A Cloud-Based Patient Health Data And Analytics Platform For Pancreatic Cancer, Kawther Abdilleh, Omar Khalid, Dennis Ladnier, Wenshuai Wan, Sara Seepo, Garrett Rupp, Valentin Corelj, Zelia F Worman, Divya Sain, Jack Digiovanna, Bruce Press, Satty Chandrashekhar, Eric Collisson, Karen Y Cui, Anirban Maitra, Paul A Rejto, Kevin P White, Lynn Matrisian, Sudheer Doss

Faculty, Staff and Student Publications

Purpose: Pancreatic cancer currently holds the position of third deadliest cancer in the United States and the 5-year survival rate is among the lowest for major cancers at just 12%. Thus, continued research efforts to better understand the clinical and molecular underpinnings of pancreatic cancer are critical to developing both early detection methodologies as well as improved therapeutic options. This study introduces Pancreatic Cancer Action Network's (PanCAN's) SPARK, a cloud-based data and analytics platform that integrates patient health data from the PanCAN's research initiatives and aims to accelerate pancreatic cancer research by making real-world patient health data and analysis tools …

Harnessing Endoscopic Ultrasound-Guided Radiofrequency Ablation To Reshape The Pancreatic Ductal Adenocarcinoma Microenvironment And Elicit Systemic Immunomodulation, Vishali Moond, Bhumi Maniyar, Prateek Suresh Harne, Jennifer M Bailey-Lundberg, Nirav C Thosani

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognostics and substantial therapeutic challenges, with dismal survival rates. Tumor resistance in PDAC is primarily attributed to its fibrotic, hypoxic, and immune-suppressive tumor microenvironment (TME). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA), an Food and Drug Administration (FDA)-approved minimally invasive technique for treating pancreatic cancer, disrupts tumors with heat and induces coagulative necrosis, releasing tumor antigens that may trigger a systemic immune response-the abscopal effect. We aim to elucidate the roles of EUS-RFA-mediated thermal and mechanical stress in enhancing anti-tumor immunity in PDAC. A comprehensive literature review focused on radiofrequency immunomodulation and immunotherapy in …

Individual Ingredients Of Np-101 (Thymoquinone Formula) Inhibit Sars-Cov-2 Pseudovirus Infection, Abdelrahim Maen, Betul Gok Yavuz, Yehia I Mohamed, Abdullah Esmail, Jianming Lu, Amr Mohamed, Asfar S Azmi, Mohamed Kaseb, Osama Kasseb, Dan Li, Michelle Gocio, Mehmet Kocak, Abdelhafez Selim, Qing Ma, Ahmed O Kaseb

Faculty, Staff and Student Publications

Thymoquinone TQ, an active ingredient of Nigella Sativa, has been shown to inhibit COVID-19 symptoms in clinical trials. Thymoquinone Formulation (TQF or NP-101) is developed as a novel enteric-coated medication derivative from Nigella Sativa. TQF consists of TQ with a favorable concentration and fatty acids, including palmitic, oleic, and linoleic acids. In this study, we aimed to investigate the roles of individual ingredients of TQF on infection of SARS-CoV-2 variants