Digital Commons Network^™

The Saga Of Covid-19 In Chronic Lung Disease: History Repeats Itself, Amir Sharafkhaneh, Javad Razjouyan

Faculty, Staff and Students Publications

No abstract provided.

Central Venous Pressure And Impaired Renal Function In Children And Young Adults With Cardiovascular Disease, Jillian Olsen, Hari Tunuguntla, Alexander Alali, Swati Choudhry, Kyle D Hope, Kriti Puri, Joseph A Spinner, Ayse Akcan-Arikan, Jack F Price

Faculty, Staff and Students Publications

BACKGROUND: Traditionally, low cardiac output has been considered the primary hemodynamic driver of renal function and injury. Adult data suggest that central venous pressure (CVP) is a more important factor.

OBJECTIVES: The authors hypothesized that in children with cardiovascular disease, higher CVP predicts lower estimated glomerular filtration rate (eGFR) and worsening renal function (WRF).

METHODS: We performed a single-center cohort study of patients aged 3 months to 21 years with biventricular circulation undergoing cardiac catheterization. Pearson's correlation and linear and Cox regression analyses were performed to determine associations with eGFR at the time of catheterization and WFR within 180 days …

Microbiomes In Birds: A Review Of Links To Health And Reproduction, Mary Ann Ottinger, Shailaja Mani, Sonja Krüger, Brent Coverdale, Sandi Willows-Munro, Leigh Combrink

Faculty, Staff and Students Publications

Microbiomes have emerged as a key component essential for maintaining the health of an organism. Additionally, the roles of microbiomes are multifaceted, some unique to specific body areas and organs while others, particularly the gut microbiome, having broader effects on the entire organism. Comparative literature is emerging that compares microbiomes across mammals and birds. Domestic poultry have been the most extensively studied relative to their role in production agriculture. These data have provided a great deal of information about the effects of diet and nutritional requirements relative to the gut microbiome, productivity, and resilience to diseases. Conversely, limited research has …

An Uncommon Culprit: Trapezius Dystonia As A Cause Of Thoracic Outlet Syndrome: A Case Report, Jamie Philp, Won Jae Jeong, Paul Paily

Faculty, Staff and Students Publications

Thoracic outlet syndrome (TOS) results from compression of the neurovascular bundle in the thoracic outlet. Several etiologies can contribute to the development of thoracic outlet syndrome, including both congenital and acquired causes. Historically, trapezius pathology has not been considered a cause of TOS; however, here we report a patient with neurogenic TOS plus ipsilateral trapezius hypertonicity and hypertrophy who had significant symptomatic improvement following botulinum toxin injections to trapezius.

A Klf2-Bmper-Smad1/5 Checkpoint Regulates High Fluid Shear Stress-Mediated Artery Remodeling, Hanqiang Deng, Jiasheng Zhang, Yewei Wang, Divyesh Joshi, Xinchun Pi, Sarah De Val, Martin A Schwartz

Faculty, Staff and Students Publications

Vascular remodeling to match arterial diameter to tissue requirements commonly fails in ischemic disease. Endothelial cells sense fluid shear stress (FSS) from blood flow to maintain FSS within a narrow range in healthy vessels. Thus, high FSS induces vessel outward remodeling, but mechanisms are poorly understood. We previously reported that Smad1/5 is maximally activated at physiological FSS. Smad1/5 limits Akt activation, suggesting that inhibiting Smad1/5 may facilitate outward remodeling. Here we report that high FSS suppresses Smad1/5 by elevating KLF2, which induces the bone morphogenetic protein (BMP) pathway inhibitor, BMP-binding endothelial regulator (BMPER), thereby de-inhibiting Akt. In mice, surgically induced …

A Multimodal Deep Learning Tool For Detection Of Junctional Ectopic Tachycardia In Children With Congenital Heart Disease, Yilong Ju, Jamie L S Waugh, Satpreet Singh, Craig G Rusin, Ankit B Patel, Parag N Jain

Faculty, Staff and Students Publications

BACKGROUND: Junctional ectopic tachycardia (JET) is a prevalent life-threatening arrhythmia in children with congenital heart disease. It has a marked resemblance to normal sinus rhythm, often leading to delay in diagnosis and management.

OBJECTIVE: The study sought to develop a novel multimodal automated arrhythmia detection tool that outperforms existing JET detection tools.

METHODS: This is a cohort study performed on 40 patients with congenital heart disease at Texas Children's Hospital. Electrocardiogram and central venous pressure waveform data produced by bedside monitors are captured by the Sickbay platform. Convolutional neural networks (CNNs) were trained to classify each heartbeat as either normal …

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation Collaborative (Peace) Consensus Conference, Peta M A Alexander, Melania M Bembea, Katherine Cashen, Ira M Cheifetz, Heidi J Dalton, Adam S Himebauch, Oliver Karam, Katie M Moynihan, Marianne E Nellis, Caroline Ozment, Lakshmi Raman, Natalie E Rintoul, Ahmed S Said, Arun Saini, Marie E Steiner, Ravi R Thiagarajan, Kevin Watt, Ariane Willems, Nicole D Zantek, Ryan P Barbaro, Katherine Steffen, Adam M Vogel, Christopher Almond, Marc M Anders, Gail M Annich, Leonardo R Brandão, Wayne Chandler, Megan Delaney, Robert Digeronimo, Sitaram Emani, Samir K Gadepalli, Alejandro V Garcia, Bereketeab Haileselassie, Robert Hyslop, Martin C J Kneyber, Lisa Baumann Kreuziger, Jennifer Le, Laura Loftis, Ali B V Mcmichael, D Michael Mcmullan, Paul Monagle, Kathleen Nicol, Matthew L Paden, Jason Patregnani, John Priest, Leslie Raffini, Lindsay M Ryerson, Steven R Sloan, Jun Teruya, Andrew R Yates, Alison Gehred, Elizabeth Lyman, Jennifer A Muszynski

Faculty, Staff and Students Publications

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.

DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.

STUDY SELECTION: The management of ECMO anticoagulation for critically ill children.

DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any …

Endovascular Management Of A Ruptured Aneurysm On A Posterior Inferior Cerebellar Artery With Extradural C2-Origin: Case Report And Literature Review, Rasmus Holmboe Dahl, Gary Lloyd Horn, Zeyad Metwalli, Shankar Prakash Gopinath, Goetz Benndorf

Faculty, Staff and Students Publications

Extracranial vascular pathology uncommonly causes intracranial subarachnoid hemorrhage (SAH). Among possible lesions are aneurysms at the craniocervical junction arising from a posterior inferior cerebellar artery (PICA) with an extradural origin. We describe a case of a 55-year-old female presenting with a sudden and severe headache. A computed tomography scan revealed a SAH within the fourth ventricle and cervical spinal canal, and a ruptured saccular aneurysm on a PICA with extradural C2-origin. Despite difficult access anatomy, endovascular treatment was feasible and resulted in subtotal initial occlusion and preservation of distal PICA flow. Upon 3-month follow-up, the aneurysm was completely occluded with …

Impact Of Gut Health And Microbiome On Autism Spectrum Disorder, Sik Yu So, Tor C Savidge

Faculty, Staff and Students Publications

No abstract provided.

Enteric Fever In Children: An Epidemiological And Clinical Review Of Cases In Southeast Texas, Zachary C Foughty, Denver T Niles, Andrea T Cruz

Faculty, Staff and Students Publications

Extensively drug-resistant (XDR) strains of Salmonella enterica serotype Typhi have emerged in Pakistan and Iraq. We report 13 children with enteric fever in Southeast Texas seen over 3.5 years, of whom 23.1% had XDR isolates.

Teaching Bioinformatics Through The Analysis Of Sars-Cov-2: Project-Based Training For Computer Science Students, Pavlin G Poličar, Martin Špendl, Tomaž Curk, Blaž Zupan

Faculty, Staff and Students Publications

MOTIVATION: We learn more effectively through experience and reflection than through passive reception of information. Bioinformatics offers an excellent opportunity for project-based learning. Molecular data are abundant and accessible in open repositories, and important concepts in biology can be rediscovered by reanalyzing the data.

RESULTS: In the manuscript, we report on five hands-on assignments we designed for master's computer science students to train them in bioinformatics for genomics. These assignments are the cornerstones of our introductory bioinformatics course and are centered around the study of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). They assume no prior knowledge of molecular …

Using Human Intestinal Organoids To Understand The Small Intestine Epithelium At The Single Cell Transcriptional Level, Carolyn Bomidi, Xi-Lei Zeng, Victoria Poplaski, Cristian Coarfa, Mary K Estes, Sarah E Blutt

Faculty, Staff and Students Publications

Single cell transcriptomics has revolutionized our understanding of the cell biology of the human body. State-of-the-art human small intestinal organoid cultures provide ex vivo model systems that bridge the gap between animal models and clinical studies. The application of single cell transcriptomics to human intestinal organoid (HIO) models is revealing previously unrecognized cell biology, biochemistry, and physiology of the GI tract. The advanced single cell transcriptomics platforms use microfluidic partitioning and barcoding to generate cDNA libraries. These barcoded cDNAs can be easily sequenced by next generation sequencing platforms and used by various visualization tools to generate maps. Here, we describe …

The Frailty Trajectory's Additional Edge Over The Frailty Index: Retrospective Cohort Study Of Veterans With Heart Failure, Javad Razjouyan, Ariela R Orkaby, Molly J Horstman, Parag Goyal, Orna Intrator, Aanand D Naik

Faculty, Staff and Students Publications

No abstract provided.

A Harmonized Public Resource Of Deeply Sequenced Diverse Human Genomes, Zan Koenig, Mary T Yohannes, Lethukuthula L Nkambule, Xuefang Zhao, Julia K Goodrich, Heesu Ally Kim, Michael W Wilson, Grace Tiao, Stephanie P Hao, Nareh Sahakian, Katherine R Chao, Mark A Walker, Yunfei Lyu, Heidi L Rehm, Benjamin M Neale, Michael E Talkowski, Mark J Daly, Harrison Brand, Konrad J Karczewski, Elizabeth G Atkinson, Alicia R Martin

Faculty, Staff and Students Publications

Underrepresented populations are often excluded from genomic studies owing in part to a lack of resources supporting their analyses. The 1000 Genomes Project (1kGP) and Human Genome Diversity Project (HGDP), which have recently been sequenced to high coverage, are valuable genomic resources because of the global diversity they capture and their open data sharing policies. Here, we harmonized a high-quality set of 4094 whole genomes from 80 populations in the HGDP and 1kGP with data from the Genome Aggregation Database (gnomAD) and identified over 153 million high-quality SNVs, indels, and SVs. We performed a detailed ancestry analysis of this cohort, …

Neuropsychological Profiles Of Deployment-Related Mild Traumatic Brain Injury: A Limbic-Cenc Study, Nicola L De Souza, Hannah M Lindsey, Katherine Dorman, Emily L Dennis, Eamonn Kennedy, Deleene S Menefee, J Scott Parrott, Yuane Jia, Mary Jo V Pugh, William C Walker, David F Tate, David X Cifu, Jason M Bailie, Nicholas D Davenport, Sarah L Martindale, Maya O'Neil, Jared A Rowland, Randall S Scheibel, Scott R Sponheim, Maya Troyanskaya, Elisabeth A Wilde, Carrie Esopenko

Faculty, Staff and Students Publications

Background and objectives: Traumatic brain injury (TBI) is a concern for US service members and veterans (SMV), leading to heterogeneous psychological and cognitive outcomes. We sought to identify neuropsychological profiles of mild TBI (mTBI) and posttraumatic stress disorder (PTSD) among the largest SMV sample to date.

Methods: We analyzed cross-sectional baseline data from SMV with prior combat deployments enrolled in the ongoing Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium prospective longitudinal study. Latent profile analysis identified symptom profiles using 35 indicators, including physical symptoms, depression, quality of life, sleep quality, postconcussive symptoms, and cognitive performance. It …

Correction: Rebuilding The Health Sector In Gaza: Alternative Humanitarian Voices, Karl Blanchet, Martine Najem, Lina Shadid, Rouba Ali Fehmi, Fawzi Al Hammouri, Ghassan Saed, Khaled J Saleh, Mosab Nasser, Nidal Moukaddam, Jonathan Polonsky, Omar Lattouf

Faculty, Staff and Students Publications

No abstract provided.

What Questions Do Patients Ask About Biologic Therapies For Chronic Sinusitis With Nasal Polyps?, Samuel E Razmi, Lexi Goehring, Aatin K Dhanda, Jason Shenoi, Faizaan Khan, Keyvon Rashidi, Daniel Gorelik, Kenneth R Sims, Meha G Fox, Masayoshi Takashima, Omar G Ahmed

Faculty, Staff and Students Publications

Objective: The objective of this study is to explore the questions commonly asked online about biologic therapies for use in treatment of chronic sinusitis with nasal polyps (CRSwNP) and the quality of the available content.

Methods: Most common search terms were identified via Google Trends. People Also Ask (PAA) questions were identified and extracted with their associated website using an online data-scraping program [Search Engine Optimization (SEO) Minion, Keywords Everywhere]. Sources were evaluated using Flesch Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE, higher number = better) score for readability; Journal of American Medical Association (JAMA) Benchmark …

Neuroimaging Of Vermiform Giant Arachnoid Granulations In Children, Oswaldo A Guevara Tirado, Livja Mertiri, Stephen F Kralik, Nilesh K Desai, Thierry A G M Huisman, Maarten H Lequin, Huy Brandon D Tran

Faculty, Staff and Students Publications

Arachnoid granulations (AGs) are generally benign structures within the subarachnoid space that extend into the dural sinuses and calvarial bone. They can present in a variety of sizes but are termed 'giant' arachnoid granulations (GAGs) when they are larger than 1 cm in diameter or take up a significant portion of the dural sinus' lumen. Vermiform giant arachnoid granulations are a specific type of GAG that are known for their worm-like appearance. Specifically, these vermiform GAGs can be challenging to diagnose as they can mimic other pathologies like dural sinus thrombosis, sinus cavernomas, or brain tumors. In this case series, …

Mental Health Assessments For Fetal Interventions, Sindhura Vangala, Roy Williams, Cara M Buskmiller, Jessian L Munoz

Faculty, Staff and Students Publications

No abstract provided.

Methphaser: Methylation-Based Long-Read Haplotype Phasing Of Human Genomes, Yilei Fu, Sergey Aganezov, Medhat Mahmoud, John Beaulaurier, Sissel Juul, Todd J Treangen, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The assignment of variants across haplotypes, phasing, is crucial for predicting the consequences, interaction, and inheritance of mutations and is a key step in improving our understanding of phenotype and disease. However, phasing is limited by read length and stretches of homozygosity along the genome. To overcome this limitation, we designed MethPhaser, a method that utilizes methylation signals from Oxford Nanopore Technologies to extend Single Nucleotide Variation (SNV)-based phasing. We demonstrate that haplotype-specific methylations extensively exist in Human genomes and the advent of long-read technologies enabled direct report of methylation signals. For ONT R9 and R10 cell line data, we …

Identifying Interventions To Improve Diagnostic Safety In Emergency Departments: Protocol For A Participatory Design Study, Woosuk Seo, Sun Young Park, Zhan Zhang, Hardeep Singh, Kalyan Pasupathy, Prashant Mahajan

Faculty, Staff and Students Publications

Background: Emergency departments (EDs) are complex and fast-paced clinical settings where a diagnosis is made in a time-, information-, and resource-constrained context. Thus, it is predisposed to suboptimal diagnostic outcomes, leading to errors and subsequent patient harm. Arriving at a timely and accurate diagnosis is an activity that occurs after an effective collaboration between the patient or caregiver and the clinical team within the ED. Interventions such as novel sociotechnical solutions are needed to mitigate errors and risks.

Objective: This study aims to identify challenges that frontline ED health care providers and patients face in the ED diagnostic process and …

Esr1 And P53 Interactome Alteration Defines Mechanisms Of Tamoxifen Response In Luminal Breast Cancer, Chetan C Oturkar, Spencer R Rosario, Alan D Hutson, Adrianne Groman, Stephen B Edge, Carl D Morrison, Wendy M Swetzig, Jianmin Wang, Jun Hyoung Park, Benny Abraham Kaipparettu, Prashant K Singh, Shicha Kumar, Helen H Cappuccino, Manish Ranjan, Araba Adjei, Mohammad Ghasemi, Andrew K L Goey, Swati Kulkarni, Gokul M Das

Faculty, Staff and Students Publications

The canonical mechanism behind tamoxifen's therapeutic effect on estrogen receptor α/ESR1+ breast cancers is inhibition of ESR1-dependent estrogen signaling. Although ESR1+ tumors expressing wild-type p53 were reported to be more responsive to tamoxifen (Tam) therapy, p53 has not been factored into choice of this therapy and the mechanism underlying the role of p53 in Tam response remains unclear. In a window-of-opportunity trial on patients with newly diagnosed stage I-III ESR1+/HER2/wild-type p53 breast cancer who were randomized to arms with or without Tam prior to surgery, we reveal that the ESR1-p53 interaction in tumors was inhibited by Tam. This resulted in …

Alzheimer's Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Analyzing Efficiency Of A Lentiviral Shrna Knockdown System In Human Enteroids Using Western Blot And Flow Cytometry, Adam P Wilson, Karni S Moshal, Addison P Franca, Sasirekha Ramani, Randle Gallucci, Hala Chaaban, Kathryn Y Burge

Faculty, Staff and Students Publications

Enteroids are in vitro models to study gastrointestinal pathologies and test personalized therapeutics; however, the inherent complexity of enteroids often renders standard gene editing approaches ineffective. Here, we introduce a refined lentiviral transfection protocol, ensuring sufficient lentiviral engagement with enteroids while considering spatiotemporal growth variability throughout the extracellular matrix. Additionally, we highlight a selection process for transduced cells, introduce a protocol to accurately measure transduction efficiency, and explore methodologies to gauge effects of gene knockdown on biological processes.

Comprehensive Single-Cell Atlas Of The Mouse Retina, Jin Li, Jongsu Choi, Xuesen Cheng, Justin Ma, Shahil Pema, Joshua R Sanes, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran, Yumei Li, Rui Chen

Faculty, Staff and Students Publications

Single-cell RNA sequencing (scRNA-seq) has advanced our understanding of cellular heterogeneity by characterizing cell types across tissues and species. While several mouse retinal scRNA-seq datasets exist, each dataset is either limited in cell numbers or focused on specific cell classes, thereby hindering comprehensive gene expression analysis across all retina types. To fill the gap, we generated the largest retinal scRNA-seq dataset to date, comprising approximately 190,000 single cells from C57BL/6J mouse retinas, enriched for rare population cells via antibody-based magnetic cell sorting. Integrating this dataset with public datasets, we constructed the Mouse Retina Cell Atlas (MRCA) for wild-type mice, encompassing …

Initiation Of Hnrnpa1 Low-Complexity Domain Condensation Monitored By Dynamic Light Scattering, Phoebe S Tsoi, Josephine C Ferreon, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Biomolecular condensates (BMCs) exhibit physiological and pathological relevance in biological systems. Both liquid and solid condensates play significant roles in the spatiotemporal regulation and organization of macromolecules and their biological activities. Some pathological solid condensates, such as Lewy Bodies and other fibrillar aggregates, have been hypothesized to originate from liquid condensates. With the prevalence of BMCs having functional and dysfunctional roles, it is imperative to understand the mechanism of biomolecular condensate formation and initiation. Using the low-complexity domain (LCD) of heterogenous ribonuclear protein A1 (hnRNPA1) as our model, we monitored initial assembly events using dynamic light scattering (DLS) while modulating …

Protocol For Optical, Aqueous-Based Clearing Of Murine Tissues Using Ez Clear, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Protocol For Preclinical Evaluation Of Locoregionally Delivered Car T Cells In Patient-Derived Xenograft Models Of Brain Tumors, Benjamin Draper, Chantelle Bowers, Eleni Vassalou, Ailsa Greppi, John Anderson, Nabil Ahmed, Michael D Taylor, Laura K Donovan

Faculty, Staff and Students Publications

Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections. In line with clinical trial procedures, our protocol broadens available treatment modalities for direct clinical translation. For complete details on the use and execution of this protocol, please refer to Donovan et al …

Integration Of Ζ-Deficient Cars Into The Cd3Ζ Gene Conveys Potent Cytotoxicity In T And Nk Cells, Jonas Kath, Clemens Franke, Vanessa Drosdek, Weijie Du, Viktor Glaser, Carla Fuster-Garcia, Maik Stein, Tatiana Zittel, Sarah Schulenberg, Caroline E Porter, Lena Andersch, Annette Künkele, Joshua Alcaniz, Jens Hoffmann, Hinrich Abken, Mohamed Abou-El-Enein, Axel Pruß, Masataka Suzuki, Toni Cathomen, Renata Stripecke, Hans-Dieter Volk, Petra Reinke, Michael Schmueck-Henneresse, Dimitrios L Wagner

Faculty, Staff and Students Publications

Chimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in nonphysiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs and biosafety requirements. Random gene transfer modalities pose a risk of malignant transformation by insertional mutagenesis. Here, we propose a novel approach utilizing CRISPR-Cas gene editing to redirect T cells and natural killer (NK) cells with CARs. By transferring shorter, truncated CAR-transgenes lacking a main activation domain into the human CD3ζ (CD247) …

Rejection Resistant Cd30car-Modified Epstein-Barr Virus-Specific T Cells As An Off-The-Shelf Platform For Cd30+ Lymphoma, David H Quach, Haran R Ganesh, Yolanda D Briones, Nazila Nouraee, Audrey Ma, Yezan F Hadidi, Sandhya Sharma, Cliona M Rooney

Faculty, Staff and Students Publications

Off-the-shelf (OTS) adoptive T cell therapies have many benefits such as immediate availability, improved access and reduced cost, but face the major challenges of graft-vs-host disease (GVHD) and graft rejection, mediated by alloreactive T cells present in the graft and host, respectively. We have developed a platform for OTS T cell therapies by using Epstein-Bar virus (EBV)-specific T cells (EBVSTs) expressing a chimeric antigen receptor (CAR) targeting CD30. Allogeneic EBVSTs have not caused GVHD in several clinical trials, while the CD30.CAR, that is effective for the treatment of lymphoma, can also target alloreactive T cells that upregulate CD30 on activation. …