Biomedical Informatics Commons^™

Interleukin-15-Armoured Gpc3 Car T Cells For Patients With Solid Cancers, David Steffin, Nisha Ghatwai, Antonino Montalbano, Purva Rathi, Amy N Courtney, Azlann B Arnett, Julien Fleurence, Ramy Sweidan, Tao Wang, Huimin Zhang, Prakash Masand, John M Maris, Daniel Martinez, Jennifer Pogoriler, Navin Varadarajan, Sachin G Thakkar, Deborah Lyon, Natalia Lapteva, Mei Zhuyong, Kalyani Patel, Dolores Lopez-Terrada, Carlos A Ramos, Premal Lulla, Tannaz Armaghany, Bambi J Grilley, Stephen Gottschalk, Gianpietro Dotti, Leonid S Metelitsa, Helen E Heslop, Malcolm K Brenner, Pavel Sumazin, Andras Heczey

Faculty, Staff and Students Publications

Interleukin-15 (IL15) promotes the survival of T lymphocytes and enhances the antitumor properties of CAR T cells in preclinical models of solid neoplasms in which CAR T cells have limited efficacy1-4. Glypican-3 (GPC3) is expressed in a group of solid cancers5-10, and here we report the first evaluation in humans of the effects of IL15 co-expression on GPC3-CAR T cells. Cohort 1 patients (NCT02905188/NCT02932956) received GPC3-CAR T cells, which were safe but produced no objective antitumor responses and reached peak expansion at two weeks. Cohort 2 patients ( …

Mapping The Functional Network Of Human Cancer Through Machine Learning And Pan-Cancer Proteogenomics, Zhiao Shi, Jonathan T Lei, John M Elizarraras, Bing Zhang

Faculty, Staff and Students Publications

Large-scale omics profiling has uncovered a vast array of somatic mutations and cancer-associated proteins, posing substantial challenges for their functional interpretation. Here we present a network-based approach centered on FunMap, a pan-cancer functional network constructed using supervised machine learning on extensive proteomics and RNA sequencing data from 1,194 individuals spanning 11 cancer types. Comprising 10,525 protein-coding genes, FunMap connects functionally associated genes with unprecedented precision, surpassing traditional protein-protein interaction maps. Network analysis identifies functional protein modules, reveals a hierarchical structure linked to cancer hallmarks and clinical phenotypes, provides deeper insights into established cancer drivers and predicts functions for understudied cancer-associated …

Establishing Standardized Transthoracic Echocardiography Reference Ranges For Mouse Models: Insights Into The Impact Of Anesthesia, Sex, And Age, Manuela A Oestereicher, Christopher S Ward, Elida Schneltzer, Susan Marschall, Helmut Fuchs, Valerie Gailus-Durner, Ghina Bou About, Mohammed Selloum, Hamid Meziane, Michelle Stewart, Lydia Teboul, Clare Norris, Dale Pimm, Marina Kan, Federico López Gómez, Robert Wilson, Mayra Monroy, Sheraz Pasha, Eva Zabrodska, Jan Prochazka, David Pajuelo Reguera, Zuzana Nichtova, Yann Herault, Sara Wells, Helen Parkinson, Jason D Heaney, Radislav Sedlacek, Xiang Gao, Martin Hrabe De Angelis, Nadine Spielmann

Faculty, Staff and Students Publications

Introduction: Mouse models play a critical role in cardiology research, offering valuable insights into the molecular mechanisms, genetics, and potential treatments for cardiovascular diseases. However, the ability to transfer findings in mice between studies is limited by the absence of standardized protocols and valid reference values for the assessment of normal cardiac function in mice. This study aims to establish comprehensive transthoracic echocardiography (TTE) reference ranges for mice, particularly focusing on C57BL/6N wild-type controls.

Methods: The study, which includes data from over 15,000 mice through the International Mouse Phenotyping Consortium (IMPC), highlights how variables such as sex, age, body weight, …

Designing And Implementing Solution-Oriented Team Science Initiatives-A Chronic Pain Example, Nele A Haelterman, Armen N Akopian, Kyle D Allen, Yenisel Cruz-Almeida, Christopher R Donnelly, Brendan Lee, Rebecca Lenzi, Anne-Marie Malfait, Marie Mancini, Maryann E Martone, Joost B Wagenaar, Kim C Worley

Faculty, Staff and Students Publications

Large, collaborative projects that combine researchers from multiple scientific disciplines have become an integral part of the scientific endeavor. While transdisciplinary team science projects hold great potential, they also come with a unique set of challenges compared to monodisciplinary projects. The Science of Team Science (SciTS) field has developed multiple conceptual models and frameworks that guide the design, implementation, and evaluation of team science initiatives to maximize their potential for making breakthrough discoveries and creating solutions for complex problems. While these conceptual models contain a trove of valuable information for successful team science, guidance on how to effectively implement them …

Nanoparticle Contrast Agents For Photon-Counting Computed Tomography: Recent Developments And Future Opportunities, Laxman Devkota, Rohan Bhavane, Cristian T Badea, Eric A Tanifum, Ananth V Annapragada, Ketan B Ghaghada

Faculty, Staff and Students Publications

The clinical availability of photon-counting computed tomography (PCCT) has ushered in a new era of CT imaging. Spectral imaging coupled with superior contrast resolution, and ultrahigh spatial resolution (200 μm) offered by PCCT has the potential to revolutionize value-driven imaging. The potential of multicolor PCCT has generated excitement, and renewed interest, in novel contrast agent development for comprehensive disease interrogation, prediction and monitoring of treatment outcomes. Nanoparticles provide a versatile and powerful platform for the development of next generation contrast agents for spectral PCCT. In this article, we review recent developments and use of nanoparticle contrast agents for PCCT. We …

Exercise Mitigates High-Fat Diet-Induced Cardiac Dysfunction Via Apoe Genotype- And Immune-Dependent Mechanisms: A Photon-Counting Ct Study In Adult Mice, Rohan Nadkarni, Alex J Allphin, Darin P Clark, Yi Qi, Zay Yar Han, Ketan B Ghaghada, Alexandra Badea, Cristian T Badea

Faculty, Staff and Students Publications

Background: Cardiovascular dysfunction frequently accompanies aging and is often worsened by adverse lifestyle factors and genetic susceptibility. The apolipoprotein E (APOE) gene modulates susceptibility to cardiovascular disease, but how exercise and diet interact with APOE genotype remains insufficiently understood. We investigate the cardioprotective potential of exercise in humanized APOE-targeted replacement mice on control and high-fat diet, using photon-counting computed tomography (PCCT) and deep learning-based image segmentation.

Methods: This study included 251 male and female mice in mid-to-late life of APOE2, APOE3, and APOE4 genotypes with variation in humanized NOS2 (HN) mediated innate immune response, exercise status (exercised vs. sedentary) and …

Sex Differences In Beneficial And Pathogenic Bacteria In People With Hiv (Pwh) With A History Of Heavy Alcohol Drinking, Aakarsha V Rao, Smita S Ghare, Vasuk Gautam, Kristi L Hoffman, Joseph Petrosino, Kaku So-Armah, Jeffrey H Samet, Gregory J Patts, Debbie M Cheng, Elena Blokhina, Evgeny M Krupitsky, Dmitry Lioznov, Edwin Zvartau, Craig J Mcclain, Hillary Tindle, Matthew S Freiberg, Shirish S Barve

Faculty, Staff and Students Publications

BACKGROUND: HIV-1 infection and hazardous levels of alcohol consumption have been independently linked to gut dysbiosis affecting beneficial butyrate-producing bacteria. However, sex-based differences in the composition and function of gut microbiome of People With HIV (PWH) with a history of heavy alcohol drinking remain undetermined, which is the focus of this study.

METHODS: Cross-sectional study examining structural and functional features of the gut microbiome in PWH between men and women with a history of hazardous alcohol drinking recruited at St. Petersburg, Russia. 16S rDNA sequencing information was used for metataxonomic, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) …

An Evaluation Of Genetic Predisposition To Congenital Anomalies And Pediatric Cancer Supports, Hyunjung Gu, Yao Yu, Saumya Dushyant Sisoudiya, Pamela Mishra, He Li, Jeremy M Schraw, Michael E Scheurer, Donna M Muzny, Danielle Mitchell, Olga Taylor, Shalini N Jhangiani, Shannon Dugan-Perez, Yifan Wu, Harsha Doddapaneni, Sravya Venkata Bhamidipati, Marie-Claude Gingras, Jennifer E Posey, Richard A Gibbs, Chad D Huff, Sharon E Plon, Philip J Lupo, Aniko Sabo

Faculty, Staff and Students Publications

Purpose: Although congenital anomalies are among the strongest risk factors for developing pediatric cancer, the genetic underpinnings remain unclear. Therefore, we evaluated germline susceptibility in children with congenital anomalies and cancer.

Methods: Through the Genetic Overlap Between Anomalies and Cancer in Kids Study, we recruited 47 participants with anomalies and cancer, along with their biological families. Genome sequencing was performed, focusing on single-nucleotide variants, indels, and structural variants. Pathogenic or likely pathogenic variants were identified by the American College of Medical Genetics and Genomics classification.

Results: We identified pathogenic or likely pathogenic variants in 23.4% (11 of 47) of participants. …

Research For All: Building A Diverse Researcher Community For The All Of Us Research Program, Rubin Baskir, Minnkyong Lee, Sydney J Mcmaster, Jessica Lee, Faith Blackburne-Proctor, Romuladus Azuine, Nakia Mack, Sheri D Schully, Martin Mendoza, Janeth Sanchez, Yong Crosby, Erica Zumba, Michael Hahn, Naomi Aspaas, Ahmed Elmi, Shanté Alerté, Elizabeth Stewart, Danielle Wilfong, Meag Doherty, Margaret M Farrell, Grace B Hébert, Sula Hood, Cheryl M Thomas, Debra D Murray, Brendan Lee, Louisa A Stark, Megan A Lewis, Jen D Uhrig, Laura R Bartlett, Edgar Gil Rico, Adolph Falcón, Elizabeth Cohn, Mitchell R Lunn, Juno Obedin-Maliver, Linda Cottler, Milton Eder, Fornessa T Randal, Jason Karnes, Kitani Lemieux, Nelson Lemieux, Nelson Lemieux, Lilanta Bradley, Ronnie Tepp, Meredith Wilson, Monica Rodriguez, Chris Lunt, Karriem Watson

Faculty, Staff and Students Publications

OBJECTIVES: The NIH All of Us Research Program (All of Us) is engaging a diverse community of more than 10 000 registered researchers using a robust engagement ecosystem model. We describe strategies used to build an ecosystem that attracts and supports a diverse and inclusive researcher community to use the All of Us dataset and provide metrics on All of Us researcher usage growth.

MATERIALS AND METHODS: Researcher audiences and diversity categories were defined to guide a strategy. A researcher engagement strategy was codeveloped with program partners to support a researcher engagement ecosystem. An adapted ecological model guided the ecosystem …

Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors, Andrew C. Pearson, Jessica S. Miller, Hannah J. Jensen, Ketan Shrestha, Thomas E. Curry Jr., Diane M. Duffy

Department of Biomedical and Translational Sciences Faculty Publications

Neurotensin (NTS), a small neuropeptide, was recently established as a key paracrine mediator of ovulation. NTS mRNA is highly expressed by granulosa cells in response to the luteinizing hormone (LH) surge, and multiple NTS receptors are expressed by cells of the ovulatory follicle. To identify the role of NTS receptors NTSR1 and SORT1 in ovulation in vivo, the dominant follicle of cynomolgus macaques (Macaca fascicularis) was injected with either vehicle control, the general NTS receptor antagonist SR142948, the NTSR1-selective antagonist SR48692, or the SORT1-selective antagonist AF38469. Human chorionic gonadotropin (hCG) was then administered to initiate ovulatory events. …