Digital Commons Network^™

Magnetic Resonance Image-Based Estimates Of Hepatic Blood Flow In Children With And Without Obesity; Implications For Physiologically-Based Pharmacokinetic Models, Yoon Cho, Sherwin S. Chan, Chance S. Friesen, Valentina Shakhnovich

Research Days

Background: Physiologically based pharmacokinetic models for simulating drug pharmacokinetics are useful to guide drug dosing for pediatric patients. Hepatic blood flow could be a useful variable to use in these models.

Objectives/Goal: In this study, we explored 2-D phase contrast non-invasive magnetic resonance imaging (MRI) to measure hepatic blood flow in children with and without obesity.

Methods/Design: In this IRB-approved study, we imaged pediatric patients with abdominal MRI with 2D phase contrast imaging of the descending aorta (AO) at the diaphragm, the inferior vena cava (IVC) at the right atrium, and inferior to hepatic drainage above the renal vein confluence …

A Computationally Designed Ace2 Decoy Has Broad Efficacy Against Sars-Cov-2 Omicron Variants And Related Viruses In Vitro And In Vivo, Brandon Havranek, Graeme Walker Lindsey, Yusuke Higuchi, Yumi Itoh, Tatsuya Suzuki, Toru Okamoto, Atsushi Hoshino, Erik Procko, Shahidul M. Islam

SKMC Student Presentations and Publications

SARS-CoV-2, especially B.1.1.529/omicron and its sublineages, continues to mutate to evade monoclonal antibodies and antibodies elicited by vaccination. Affinity-enhanced soluble ACE2 (sACE2) is an alternative strategy that works by binding the SARS-CoV-2 S protein, acting as a 'decoy' to block the interaction between the S and human ACE2. Using a computational design strategy, we designed an affinity-enhanced ACE2 decoy, FLIF, that exhibited tight binding to SARS-CoV-2 delta and omicron variants. Our computationally calculated absolute binding free energies (ABFE) between sACE2:SARS-CoV-2 S proteins and their variants showed excellent agreement to binding experiments. FLIF displayed robust therapeutic utility against a broad range …

Safety And Efficacy Of Fecal Microbiota Transplantation In Treatment Of Inflammatory Bowel Disease In The Pediatric Population: A Systematic Review And Meta-Analysis, Mark Hsu, Kyaw Min Tun, Kavita Batra, Lubaba Haque, Tahne Vongsavath, Annie S. Hong Md

School of Medicine Faculty Research

Background and Aims: Fecal microbiota transplantation (FMT) has been increasingly studied in the inflammatory bowel disease (IBD) population. However, most studies have focused on the adult population, and the safety and efficacy of FMT in a pediatric population is less well understood. This systematic review and meta-analysis investigates the safety and efficacy of FMT in a pediatric IBD population.

Methods: A comprehensive literature search of publications published prior to 30 June 2022 was undertaken. Safety data, IBD-related outcomes, and microbiome analysis were obtained from these studies when accessible. Individual estimates of each study were pooled, and sensitivity analysis was conducted. …

Dynamic Role Of Exosome Micrornas In Cancer Cell Signaling And Their Emerging Role As Noninvasive Biomarkers, Jaya Aseervatham

Department of Neurology Faculty Papers

Exosomes are extracellular vesicles that originate from endosomes and are released by all cells irrespective of their origin or type. They play an important role in cell communication and can act in an autocrine, endocrine, or paracrine fashion. They are 40–150 nm in diameter and have a similar composition to the cell of origin. An exosome released by a particular cell is unique since it carries information about the state of the cell in pathological conditions such as cancer. miRNAs carried by cancer-derived exosomes play a multifaceted role by taking part in cell proliferation, invasion, metastasis, epithelial–mesenchymal transition, angiogenesis, apoptosis, …

Mitochondrial Dysfunction: At The Nexus Between Alcohol-Associated Immunometabolic Dysregulation And Tissue Injury, Robert W. Siggins, Patrick M. Mcternan, Liz Simon, Flavia M. Souza-Smith, Patricia E. Molina

School of Medicine Faculty Publications

Alcohol misuse, directly or indirectly as a result of its metabolism, negatively impacts most tissues, including four with critical roles in energy metabolism regulation: the liver, pancreas, adipose, and skeletal muscle. Mitochondria have long been studied for their biosynthetic roles, such as ATP synthesis and initiation of apoptosis. However, current research has provided evidence that mitochondria participate in myriad cellular processes, including immune activation, nutrient sensing in pancreatic β-cells, and skeletal muscle stem and progenitor cell differentiation. The literature indicates that alcohol impairs mitochondrial respiratory capacity, promoting reactive oxygen species (ROS) generation and disrupting mitochondrial dynamics, leading to dysfunctional mitochondria …

Clinical Characteristics And Survival Of Pulmonary Arterial Hypertension With Or Without Interstitial Lung Disease In Systemic Sclerosis, Jessica L Fairley, Dylan Hansen, Laura Ross, Susanna Proudman, Joanne Sahhar, Gene-Siew Ngian, Jennifer Walker, Lauren V Host, Kathleen Morrisroe, Diane Apostolopoulous, Nava Ferdowsi, Michelle Wilson, Maryam Tabesh, Wendy Stevens, Mandana Nikpour

Faculty, Staff and Student Publications

Objectives

To describe the clinical phenotype and prognosis of people in the Australian Scleroderma (SSc) Cohort Study with pulmonary arterial hypertension (PAH) with or without interstitial lung disease (ILD).

Methods

Participants meeting ACR/EULAR criteria for SSc were divided into four mutually exclusive groups: those meeting criteria for PAH (PAH-only), ILD (ILD-only), concurrent PAH and ILD (PAH-ILD) or neither PAH nor ILD (SSc-only). Logistic or linear regression analyses were used for associations between clinical features, health-related quality of life (HRQoL) and physical function. Survival analysis was performed using Kaplan–Meier estimates and Cox-regression modelling.

Results

Of 1561 participants, 7% fulfilled criteria for …

Efficient Cancer Modeling Through Crispr-Cas9/Hdr-Based Somatic Precision Gene Editing In Mice, Wen Bu, Chad J Creighton, Kelsey S Heavener, Carolina Gutierrez, Yongchao Dou, Amy T Ku, Yiqun Zhang, Weiyu Jiang, Jazmin Urrutia, Wen Jiang, Fei Yue, Luyu Jia, Ahmed Atef Ibrahim, Bing Zhang, Shixia Huang, Yi Li

Faculty, Staff and Student Publications

CRISPR-Cas9 has been used successfully to introduce indels in somatic cells of rodents; however, precise editing of single nucleotides has been hampered by limitations of flexibility and efficiency. Here, we report technological modifications to the CRISPR-Cas9 vector system that now allows homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic tissues to generate tumor models with high flexibility and efficiency. Somatic editing of either

3-Phosphoinositide-Dependent Kinase 1 Drives Acquired Resistance To Osimertinib, Ismail M Meraz, Mourad Majidi, Bingliang Fang, Feng Meng, Lihui Gao, Ruping Shao, Renduo Song, Feng Li, Yonathan Lissanu, Huiqin Chen, Min Jin Ha, Qi Wang, Jing Wang, Elizabeth Shpall, Sung Yun Jung, Franziska Haderk, Philippe Gui, Jonathan Wesley Riess, Victor Olivas, Trever G Bivona, Jack A Roth

Faculty, Staff and Students Publications

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of …

A Conditional Strategy For Cell-Type-Specific Labeling Of Endogenous Excitatory Synapses In Drosophila, Michael J. Parisi, Michael A. Aimino, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Chemical neurotransmission occurs at specialized contacts where neurotransmitter release machinery apposes neurotransmitter receptors to underlie circuit function. A series of complex events underlies preand postsynaptic protein recruitment to neuronal connections. To better study synaptic development in individual neurons, we need cell-type-specific strategies to visualize endogenous synaptic proteins. Although presynaptic strategies exist, postsynaptic proteins remain less studied because of a paucity of cell-type-specific reagents. To study excitatory postsynapses with cell-type specificity, we engineered dlg1[4K], a conditionally labeled marker of Drosophila excitatory postsynaptic densities. With binary expression systems, dlg1[4K] labels central and peripheral postsynapses in larvae and adults. Using dlg1[4K], we find …

Meqtl Mapping In The Genoa Study Reveals Genetic Determinants Of Dna Methylation In African Americans, Lulu Shang, Wei Zhao, Yi Zhe Wang, Zheng Li, Jerome J Choi, Minjung Kho, Thomas H Mosley, Sharon L R Kardia, Jennifer A Smith, Xiang Zhou

Faculty, Staff and Student Publications

Identifying genetic variants that are associated with variation in DNA methylation, an analysis commonly referred to as methylation quantitative trait locus (meQTL) mapping, is an important first step towards understanding the genetic architecture underlying epigenetic variation. Most existing meQTL mapping studies have focused on individuals of European ancestry and are underrepresented in other populations, with a particular absence of large studies in populations with African ancestry. We fill this critical knowledge gap by performing a large-scale cis-meQTL mapping study in 961 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We identify a total of 4,565,687 cis-acting meQTLs …

Effects Of A Commercially Available Acoustic Vibration Device On Nasal Symptoms, Pulmonary Function, And Exercise Performance, Catherine M. Cavallaro

Masters Theses, 2020-current

Purpose: The purpose of this study was to investigate whether the SinuSonic acoustic vibration device influenced nasal symptoms and function, expired nitric oxide (eNO), pulmonary function, and exercise responses and performance in active individuals. Methods: Sixteen recreational exercisers (age 34.5 ± 16.0 y: VO_2max 41.1 ± 6.5 mL/kg/min) completed two exercise trials, each consisting of a 10 min warm up followed by a graded exercise test on a cycle ergometer. In a randomized, counterbalanced design, participants used a SinuSonic device (or sham device) for 5 min, followed by 5 min of rest, before undergoing the graded exercise test. Nasal …

Five-Year Follow-Up Of Zuma-1 Supports The Curative Potential Of Axicabtagene Ciloleucel In Refractory Large B-Cell Lymphoma, Sattva S Neelapu, Caron A Jacobson, Armin Ghobadi, David B Miklos, Lazaros J Lekakis, Olalekan O Oluwole, Yi Lin, Ira Braunschweig, Brian T Hill, John M Timmerman, Abhinav Deol, Patrick M Reagan, Patrick Stiff, Ian W Flinn, Umar Farooq, Andre H Goy, Peter A Mcsweeney, Javier Munoz, Tanya Siddiqi, Julio C Chavez, Alex F Herrera, Nancy L Bartlett, Adrian A Bot, Rhine R Shen, Jinghui Dong, Kanwarjit Singh, Harry Miao, Jenny J Kim, Yan Zheng, Frederick L Locke

Faculty, Staff and Student Publications

In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% …

Rational Design Of Highly Potent And Selective Covalent Map2k7 Inhibitors, Dalton R Kim, Meghan J Orr, Ada J Kwong, Kristine K Deibler, Hasan H Munshi, Cory Seth Bridges, Taylor Jie Chen, Xiaoyu Zhang, H Daniel Lacorazza, Karl A Scheidt

Faculty, Staff and Students Publications

The mitogen-activated protein kinase signaling cascade is conserved across eukaryotes, where it plays a critical role in the regulation of activities including proliferation, differentiation, and stress responses. This pathway propagates external stimuli through a series of phosphorylation events, which allows external signals to influence metabolic and transcriptional activities. Within the cascade, MEK, or MAP2K, enzymes occupy a molecular crossroads immediately upstream to significant signal divergence and cross-talk. One such kinase, MAP2K7, also known as MEK7 and MKK7, is a protein of great interest in the molecular pathophysiology underlying pediatric T cell acute lymphoblastic leukemia (T-ALL). Herein, we describe the rational …

Co-Clinical Imaging Metadata Information (Cimi) For Cancer Research To Promote Open Science, Standardization, And Reproducibility In Preclinical Imaging, Stephen M Moore, James D Quirk, Andrew W Lassiter, Richard Laforest, Gregory D Ayers, Cristian T Badea, Andriy Y Fedorov, Paul E Kinahan, Matthew Holbrook, Peder E Z Larson, Renuka Sriram, Thomas L Chenevert, Dariya Malyarenko, John Kurhanewicz, A Mcgarry Houghton, Brian D Ross, Stephen Pickup, James C Gee, Rong Zhou, Seth T Gammon, Henry Charles Manning, Raheleh Roudi, Heike E Daldrup-Link, Michael T Lewis, Daniel L Rubin, Thomas E Yankeelov, Kooresh I Shoghi

Faculty, Staff and Students Publications

Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute's (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an …

Ppigcf: A Protein-Protein Interaction-Based Gene Correlation Filter For Optimal Gene Selection, Soumen Kumar Pati, Manan Kumar Gupta, Ayan Banerjee, Saurav Mallik, Zhongming Zhao

Faculty, Staff and Student Publications

Biological data at the omics level are highly complex, requiring powerful computational approaches to identifying significant intrinsic characteristics to further search for informative markers involved in the studied phenotype. In this paper, we propose a novel dimension reduction technique, protein-protein interaction-based gene correlation filtration (PPIGCF), which builds on gene ontology (GO) and protein-protein interaction (PPI) structures to analyze microarray gene expression data. PPIGCF first extracts the gene symbols with their expression from the experimental dataset, and then, classifies them based on GO biological process (BP) and cellular component (CC) annotations. Every classification group inherits all the information on its CCs, …

Sleep Problems In Old Age: Metabotropic Glutamate Receptor To The Rescue, Sho Inami, Dinis J.S. Afonso, Kyunghee Koh

Farber Institute for Neuroscience Faculty Papers

No abstract provided.

Sensor-Controlled Digital Game For Heart Failure Self-Management: Protocol For A Randomized Controlled Trial, Kavita Radhakrishnan, Christine Julien, Matthew O'Hair, Rachel Tunis, Grace Lee, Angelica Rangel, James Custer, Tom Baranowski, Paul J Rathouz, Miyong T Kim

Faculty, Staff and Students Publications

BACKGROUND: Heart failure (HF) is the leading cause of hospitalization among older adults in the United States. There are substantial racial and geographic disparities in HF outcomes, with patients living in southern US states having a mortality rate 69% higher than the national average. Self-management behaviors, particularly daily weight monitoring and physical activity, are extremely important in improving HF outcomes; however, patients typically have particularly low adherence to these behaviors. With the rise of digital technologies to improve health outcomes and motivate health behaviors, sensor-controlled digital games (SCDGs) have become a promising approach. SCDGs, which leverage sensor-connected technologies, offer the …

Exrna-Eclip Intersection Analysis Reveals A Map Of Extracellular Rna Binding Proteins And Associated Rnas Across Major Human Biofluids And Carriers, Emily L Laplante, Alessandra Stürchler, Robert Fullem, David Chen, Anne C Starner, Emmanuel Esquivel, Eric Alsop, Andrew R Jackson, Ionita Ghiran, Getulio Pereira, Joel Rozowsky, Justin Chang, Mark B Gerstein, Roger P Alexander, Matthew E Roth, Jeffrey L Franklin, Robert J Coffey, Robert L Raffai, Isabelle M Mansuy, Stavros Stavrakis, Andrew J Demello, Louise C Laurent, Yi-Ting Wang, Chia-Feng Tsai, Tao Liu, Jennifer Jones, Kendall Van Keuren-Jensen, Eric Van Nostrand, Bogdan Mateescu, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small …

Brexucabtagene Autoleucel For Relapsed Or Refractory Mantle Cell Lymphoma In Standard-Of-Care Practice: Results From The Us Lymphoma Car T Consortium, Yucai Wang, Preetesh Jain, Frederick L Locke, Matthew J Maurer, Matthew J Frank, Javier L Munoz, Saurabh Dahiya, Amer M Beitinjaneh, Miriam T Jacobs, Joseph P Mcguirk, Julie M Vose, Andre Goy, Charalambos Andreadis, Brian T Hill, Kathleen A Dorritie, Olalekan O Oluwole, Abhinav Deol, Jonas Paludo, Bijal Shah, Trent Wang, Rahul Banerjee, David B Miklos, Aaron P Rapoport, Lazaros Lekakis, Armin Ghobadi, Sattva S Neelapu, Yi Lin, Michael L Wang, Michael D Jain

Faculty, Staff and Student Publications

Purpose: Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication.

Patients and methods: Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of …

Immune Checkpoint B7-H3 Is A Therapeutic Vulnerability In Prostate Cancer Harboring Pten And Tp53 Deficiencies, Wei Shi, Yin Wang, Yuehui Zhao, Justin Jimin Kim, Haoyan Li, Chenling Meng, Feiyu Chen, Jie Zhang, Duncan H Mak, Vivien Van, Javier Leo, Brad St Croix, Ana Aparicio, Di Zhao

Faculty, Staff and Student Publications

Checkpoint immunotherapy has yielded meaningful responses across many cancers but has shown modest efficacy in advanced prostate cancer. B7 homolog 3 protein (B7-H3/CD276) is an immune checkpoint molecule and has emerged as a promising therapeutic target. However, much remains to be understood regarding B7-H3's role in cancer progression, predictive biomarkers for B7-H3-targeted therapy, and combinatorial strategies. Our multi-omics analyses identified B7-H3 as one of the most abundant immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Here, we sought in vivo genetic evidence for, and mechanistic understanding of, the role of B7-H3 in PTEN/TP53-deficient prostate …

Late Health Outcomes Among Survivors Of Wilms Tumor Diagnosed Over Three Decades: A Report From The Childhood Cancer Survivor Study, Brent R Weil, Andrew J Murphy, Qi Liu, Rebecca M Howell, Susan A Smith, Christopher B Weldon, Elizabeth A Mullen, Arin L Madenci, Wendy M Leisenring, Joseph P Neglia, Lucie M Turcotte, Kevin C Oeffinger, Amanda M Termuhlen, Sogol Mostoufi-Moab, Jennifer M Levine, Kevin R Krull, Yutaka Yasui, Leslie L Robison, Gregory T Armstrong, Eric J Chow, Saro H Armenian

Faculty, Staff and Student Publications

Purpose: To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens.

Methods: Cumulative incidence of late mortality (≥ 5 years from diagnosis) and chronic health conditions (CHCs) were evaluated in WT survivors from the Childhood Cancer Survivor Study. Outcomes were evaluated by treatment, including nephrectomy combined with vincristine and actinomycin D (VA), VA + doxorubicin + abdominal radiotherapy (VAD + ART), VAD + ART + whole lung radiotherapy, or receipt of ≥ 4 chemotherapy agents.

Results: Among 2,008 unilateral WT survivors, 142 deaths occurred (standardized mortality ratio, 2.9, 95% CI, 2.5 to …

Phase Ii Trial Of Neoadjuvant Sitravatinib Plus Nivolumab In Patients Undergoing Nephrectomy For Locally Advanced Clear Cell Renal Cell Carcinoma, Jose A Karam, Pavlos Msaouel, Cara L Haymaker, Surena F Matin, Matthew T Campbell, Amado J Zurita, Amishi Y Shah, Ignacio I Wistuba, Enrica Marmonti, Dzifa Y Duose, Edwin R Parra, Luisa Maren Solis Soto, Caddie Laberiano-Fernandez, Marisa Lozano, Alice Abraham, Max Hallin, Curtis D Chin, Peter Olson, Hirak Der-Torossian, Xiaohong Yan, Nizar M Tannir, Christopher G Wood

Faculty, Staff and Student Publications

Sitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 inhibitors such as nivolumab. We report a single-arm, interventional, phase 2 study of neoadjuvant sitravatinib in combination with nivolumab in patients with locally advanced clear cell renal cell carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) prior to surgery with a null hypothesis ORR = 5% and the alternative hypothesis set at ORR = 30%. Secondary endpoints were safety; pharmacokinetics (PK) of sitravatinib; immune effects, including changes in programmed cell death-ligand 1 expression; time-to-surgery; and disease-free survival …

A Stability Indicating Lc-Ms/Ms Method For Quantification Of A Nox Inhibitor R14 In Its Bisulfite Adduct Form For Pharmacokinetic Studies, Yang Wang, Jing Ma, Shiaw-Yih Lin, Huan Xie, Dong Liang

Faculty, Staff and Student Publications

R14, also known as NOX Inhibitor VII, is a potent inhibitor of NADPH oxidases (NOX) which has recently been identified as a novel agent targeting to triple-negative breast cancer. It is also rapidly degraded in collected pharmacokinetic plasma and blood samples even stored under - 70 °C. The purpose of this study was to develop a stability indicating LC-MS/MS assay that would be suitable for quantification of R14 in plasma and blood. In the presence of sodium sulfite under acidic pH, R14, an aryl lactam compound which is not a typically reactive compound for bisulfite addition, readily and completely converted …

Functional Neuronal Circuits Promote Disease Progression In Cancer, Anthony C Restaino, Austin Walz, Samuel J Vermeer, Jeffrey Barr, Attila Kovács, Robin R Fettig, Daniel W Vermeer, Hunter Reavis, Caitlin S Williamson, Christopher T Lucido, Tuany Eichwald, Dalia K Omran, Euihye Jung, Lauren E Schwartz, Maria Bell, Desirae M Muirhead, Jody E Hooper, William C Spanos, Ronny Drapkin, Sebastien Talbot, Paola D Vermeer

Faculty, Staff and Student Publications

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the …

Sirolimus Versus Cyclosporine A In Patients With Primary Acquired Pure Red Cell Aplasia: A Prospective Cohort Study, Yuan Yang, Zengwei Tang, Yuzhou Huang, Qinglin Hu, Shuqing Wang, Jiang Ji, Yali Du, Chen Yang, Miao Chen, Shimin Hu, Bing Han

Faculty, Staff and Student Publications

No abstract provided.

Pediatric Serum-Like Sickness: A Multicenter Analysis, Maya Gibson, Sarah Suppes, Jared Lovins, Emma Monique, Keith Feldman, Jennifer Goldman

Research Days

Background: Serum sickness-like reaction (SSLR) is a type III immune hypersensitivity reaction that presents 5-21 days following exposure to a medication. SSLR has nonspecific symptoms including fever, rash, and joint involvement. There are no standardized diagnostic criteria or treatment for SSLR, making this a challenging diagnosis.

Objectives/Goal: Our objective was to describe pediatric SSLR clinical manifestations, medical encounter types, and treatment strategies.

Methods/Design: A retrospective chart review across 2 freestanding children’s hospitals was used to identify patients 0-21 years of age diagnosed with SSLR by ICD-9/10 codes [T80.69XA, 999.59], SNOMED codes [1782626019, 3293325014], or pharmacovigilance review in the emergency department …

Single-Cell Transcriptome Analysis Of Xenotransplanted Human Retinal Organoids Defines Two Migratory Cell Populations Of Nonretinal Origin, Ying V Liu, Clayton P Santiago, Akin Sogunro, Gregory J Konar, Ming-Wen Hu, Minda M Mcnally, Yu-Chen Lu, Miguel Flores-Bellver, Silvia Aparicio-Domingo, Kang V Li, Zhuo-Lin Li, Dzhalal Agakishiev, Sarah E Hadyniak, Katarzyna A Hussey, Tyler J Creamer, Linda D Orzolek, Derek Teng, M Valeria Canto-Soler, Jiang Qian, Zheng Jiang, Robert J Johnston, Seth Blackshaw, Mandeep S Singh

Faculty, Staff and Students Publications

Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the …

Table Of Contents

Journal of the South Carolina Academy of Science

No abstract provided.

Polymorphisms Within Autophagy-Related Genes As Susceptibility Biomarkers For Multiple Myeloma: A Meta-Analysis Of Three Large Cohorts And Functional Characterization, Esther Clavero, José Manuel Sanchez-Maldonado, Angelica Macauda, Rob Ter Horst, Belém Sampaio-Marques, Artur Jurczyszyn, Alyssa Clay-Gilmour, Angelika Stein, Michelle A T Hildebrandt, Niels Weinhold, Gabriele Buda, Ramón García-Sanz, Waldemar Tomczak, Ulla Vogel, Andrés Jerez, Daria Zawirska, Marzena Wątek, Jonathan N Hofmann, Stefano Landi, John J Spinelli, Aleksandra Butrym, Abhishek Kumar, Joaquín Martínez-López, Sara Galimberti, María Eugenia Sarasquete, Edyta Subocz, Elzbieta Iskierka-Jażdżewska, Graham G Giles, Malwina Rybicka-Ramos, Marcin Kruszewski, Niels Abildgaard, Francisco García Verdejo, Pedro Sánchez Rovira, Miguel Inacio Da Silva Filho, Katalin Kadar, Małgorzata Razny, Wendy Cozen, Matteo Pelosini, Manuel Jurado, Parveen Bhatti, Marek Dudzinski, Agnieszka Druzd-Sitek, Enrico Orciuolo, Yang Li, Aaron D Norman, Jan Maciej Zaucha, Rui Manuel Reis, Miroslaw Markiewicz, Juan José Rodríguez Sevilla, Vibeke Andersen, Krzysztof Jamroziak, Kari Hemminki, Sonja I Berndt, Vicent Rajkumar, Grzegorz Mazur, Shaji K Kumar, Paula Ludovico, Arnon Nagler, Stephen J Chanock, Charles Dumontet, Mitchell J Machiela, Judit Varkonyi, Nicola J Camp, Elad Ziv, Annette Juul Vangsted, Elizabeth E Brown, Daniele Campa, Celine M Vachon, Mihai G Netea, Federico Canzian, Asta Försti, Juan Sainz

Faculty, Staff and Student Publications

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of …

Angiotensin Ii Receptor Inhibition Ameliorates Liver Fibrosis And Enhances Hepatocellular Carcinoma Infiltration By Effector T Cells, Li Gu, Yahui Zhu, Maiya Lee, Albert Nguyen, Nicolas T Ryujin, Jian Yu Huang, Shusil K Pandit, Shadi Chamseddine, Lianchun Xiao, Yehia I Mohamed, Ahmed O Kaseb, Michael Karin, Shabnam Shalapour

Faculty, Staff and Student Publications

Although viral hepatocellular carcinoma (HCC) is declining, nonviral HCC, which often is the end stage of nonalcoholic or alcoholic steatohepatitis (NASH, ASH), is on an upward trajectory. Immune checkpoint inhibitors (ICIs) that block the T cell inhibitory receptor PD-1 were approved for treatment of all HCC types. However, only a minority of HCC patients show a robust and sustained response to PD-1 blockade, calling for improved understanding of factors that negatively impact response rate and duration and the discovery of new adjuvant treatments that enhance ICI responsiveness. Using a mouse model of NASH-driven HCC, we identified peritumoral fibrosis as a …