Medical Genetics Commons^™

Gpr56 In Gvl: Marker Or Mechanism?, Audra N Iness, Pavan Bachireddy

Faculty, Staff and Student Publications

No abstract provided.

Correction: The Novel Phosphatase Nudt5 Is A Critical Regulator Of Triple-Negative Breast Cancer Growth, Jing Qian, Yanxia Ma, William M Tahaney, Cassandra L Moyer, Amanda Lanier, Jamal Hill, Darian Coleman, Negar Koupaei, Susan G Hilsenbeck, Michelle I Savage, Brent D G Page, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

No abstract provided.

Author Correction: Cytoskeleton Remodeling Induced By Smyd2 Methyltransferase Drives Breast Cancer Metastasis, Alexandre G Casanova, Gael S Roth, Simone Hausmann, Xiaoyin Lu, Ludivine J M Bischoff, Emilie M Froeliger, Lucid Belmudes, Ekaterina Bourova-Flin, Natasha M Flores, Ana Morales Benitez, Tourkian Chasan, Marcello Caporicci, Jessica Vayr, Sandrine Blanchet, Francesco Ielasi, Sophie Rousseaux, Pierre Hainaut, Or Gozani, Muriel Le Romancer, Yohann Couté, Andres Palencia, Pawel K Mazur, Nicolas Reynoird

Faculty, Staff and Student Publications

No abstract provided.

Integration Of Kupffer Cells Into Human Ipsc-Derived Liver Organoids For Modeling Liver Dysfunction In Sepsis, Yang Li, Yunzhong Nie, Xia Yang, Yang Liu, Xiaoshan Deng, Yoshihito Hayashi, Riana Plummer, Qinglin Li, Na Luo, Toshiharu Kasai, Takashi Okumura, Yu Kamishibahara, Takemasa Komoto, Takuya Ohkuma, Satoshi Okamoto, Yumiko Isobe, Kiyoshi Yamaguchi, Yoichi Furukawa, Hideki Taniguchi

Faculty, Staff and Student Publications

Maximizing the potential of human liver organoids (LOs) for modeling human septic liver requires the integration of innate immune cells, particularly resident macrophage Kupffer cells. In this study, we present a strategy to generate LOs containing Kupffer cells (KuLOs) by recapitulating fetal liver hematopoiesis using human induced pluripotent stem cell (hiPSC)-derived erythro-myeloid progenitors (EMPs), the origin of tissue-resident macrophages, and hiPSC-derived LOs. Remarkably, LOs actively promote EMP hematopoiesis toward myeloid and erythroid lineages. Moreover, supplementing with macrophage colony-stimulating factor (M-CSF) proves crucial in sustaining the hematopoietic population during the establishment of KuLOs. Exposing KuLOs to sepsis-like endotoxins leads to significant …

Identifying Potential Dietary Treatments For Inherited Metabolic Disorders Using Drosophila Nutrigenomics, Felipe Martelli, Jiayi Lin, Sarah Mele, Wendy Imlach, Oguz Kanca, Christopher K Barlow, Jefferson Paril, Ralf B Schittenhelm, John Christodoulou, Hugo J Bellen, Matthew D W Piper, Travis K Johnson

Faculty, Staff and Students Publications

Inherited metabolic disorders are a group of genetic conditions that can cause severe neurological impairment and child mortality. Uniquely, these disorders respond to dietary treatment; however, this option remains largely unexplored because of low disorder prevalence and the lack of a suitable paradigm for testing diets. Here, we screened 35 Drosophila amino acid disorder models for disease-diet interactions and found 26 with diet-altered development and/or survival. Using a targeted multi-nutrient array, we examine the interaction in a model of isolated sulfite oxidase deficiency, an infant-lethal disorder. We show that dietary cysteine depletion normalizes their metabolic profile and rescues development, neurophysiology, …

Extend The Benchmarking Indel Set By Manual Review Using The Individual Cell Line Sequencing Data From The Sequencing Quality Control 2 (Seqc2) Project, Binsheng Gong, Dan Li, Yifan Zhang, Rebecca Kusko, Samir Lababidi, Zehui Cao, Mingyang Chen, Ning Chen, Qiaochu Chen, Qingwang Chen, Jiacheng Dai, Qiang Gan, Yuechen Gao, Mingkun Guo, Gunjan Hariani, Yujie He, Wanwan Hou, He Jiang, Garima Kushwaha, Jian-Liang Li, Jianying Li, Yulan Li, Liang-Chun Liu, Ruimei Liu, Shiming Liu, Edwin Meriaux, Mengqing Mo, Mathew Moore, Tyler J Moss, Quanne Niu, Ananddeep Patel, Luyao Ren, Nedda F Saremi, Erfei Shang, Jun Shang, Ping Song, Siqi Sun, Brent J Urban, Danke Wang, Shangzi Wang, Zhining Wen, Xiangyi Xiong, Jingcheng Yang, Lihui Yin, Chao Zhang, Ruolan Zhang, Ambica Bhandari, Wanshi Cai, Agda Karina Eterovic, Dalila B Megherbi, Tieliu Shi, Chen Suo, Ying Yu, Yuanting Zheng, Natalia Novoradovskaya, Renee L Sears, Leming Shi, Wendell Jones, Weida Tong, Joshua Xu

Faculty, Staff and Student Publications

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly …

Correction: Detecting The Percent Of Peripheral Blood Mononuclear Cells Displaying P-Stat-3 In Malignant Glioma Patients, William Humphries, Yongtao Wang, Wei Qiao, Chantal Reina-Ortiz, Mohamed K Abou-Ghazal, Lamonne M Crutcher, Jun Wei, Ling-Yuan Kong, Raymond Sawaya, Ganesh Rao, Jeffrey Weinberg, Sujit S Prabhu, Gregory N Fuller, Amy B Heimberger

Faculty, Staff and Student Publications

No abstract provided.

Gut Microbiota Composition Is Associated With The Efficacy Of Delta-24-Rgdox In Malignant Gliomas, Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

Faculty, Staff and Student Publications

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and …

Understanding Heterogeneity In Individual Responses To Digital Lifestyle Intervention Through Self-Monitoring Adherence Trajectories In Adults With Overweight Or Obesity: Secondary Analysis Of A 6-Month Randomized Controlled Trial, Shiyu Li, Yan Du, Hongyu Miao, Kumar Sharma, Chengdong Li, Zenong Yin, Bradley Brimhall, Jing Wang

Faculty, Staff and Student Publications

Background: Achieving clinically significant weight loss through lifestyle interventions for obesity management is challenging for most individuals. Improving intervention effectiveness involves early identification of intervention nonresponders and providing them with timely, tailored interventions. Early and frequent self-monitoring (SM) adherence predicts later weight loss success, making it a potential indicator for identifying nonresponders in the initial phase.

Objective: This study aims to identify clinically meaningful participant subgroups based on longitudinal adherence to SM of diet, activity, and weight over 6 months as well as psychological predictors of participant subgroups from a self-determination theory (SDT) perspective.

Methods: This was a secondary data …

Prediabetes And Associated Risk Of Cardiovascular Events And Chronic Kidney Disease Among Adult Survivors Of Childhood Cancer In The St Jude Lifetime Cohort, Stephanie B Dixon, Fang Wang, Lu Lu, Carmen L Wilson, Daniel M Green, Thomas E Merchant, Deo Kumar Srivastava, Angela Delaney, Rebecca M Howell, John L Jefferies, Leslie L Robison, Kirsten K Ness, Melissa M Hudson, Wassim Chemaitilly, Gregory T Armstrong

Faculty, Staff and Student Publications

Purpose: Little is known about the prevalence of prediabetes and associated risk of cardiovascular events and chronic kidney disease (CKD) with this reversable condition in survivors.

Methods: Prevalence of prediabetes (fasting plasma glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.4%) and diabetes was clinically assessed in 3,529 adults ≥5 years from childhood cancer diagnosis and 448 controls stratified by age. Cox proportional hazards regression estimated progression from prediabetes to diabetes, and risk of future cardiac events, stroke, CKD, and death.

Results: Among survivors, median age 30 years (IQR, 18-65), and the prevalence of prediabetes was 29.2% (95% CI, 27.7 to 30.7) …

Summit-Fa: A New Resource For Improved Transcriptome Imputation Using Functional Annotations, Hunter J Melton, Zichen Zhang, Chong Wu

Faculty, Staff and Student Publications

Transcriptome-wide association studies (TWAS) integrate gene expression prediction models and genome-wide association studies (GWAS) to identify gene-trait associations. The power of TWAS is determined by the sample size of GWAS and the accuracy of the expression prediction model. Here, we present a new method, the Summary-level Unified Method for Modeling Integrated Transcriptome using Functional Annotations (SUMMIT-FA), which improves gene expression prediction accuracy by leveraging functional annotation resources and a large expression quantitative trait loci (eQTL) summary-level dataset. We build gene expression prediction models in whole blood using SUMMIT-FA with the comprehensive functional database MACIE and eQTL summary-level data from the …

Visual Outcome And Ocular Complications In Patients With Lacrimal Gland Carcinoma After Eye-Sparing Surgery And Adjuvant Radiation Therapy, Zhenyang Zhao, Steven Jay Frank, Jing Ning, Jiawei Zhao, Xinyang Jiang, Xin A Wang, Amy C Schefler, Ehab Hanna, Amy Moreno, Brandon Gunn, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy.

Methods: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed.

Results: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months …

Three-Dimensional Optothermal Manipulation Of Light-Absorbing Particles In Phase-Change Gel Media, Pavana Siddhartha Kollipara, Zilong Wu, Kan Yao, Dongdong Lin, Zhengyu Ju, Xiaotian Zhang, Taizhi Jiang, Hongru Ding, Jie Fang, Jingang Li, Brian A Korgel, Joan M Redwing, Guihua Yu, Yuebing Zheng

Faculty, Staff and Student Publications

Rational manipulation and assembly of discrete colloidal particles into architected superstructures have enabled several applications in materials science and nanotechnology. Optical manipulation techniques, typically operated in fluid media, facilitate the precise arrangement of colloidal particles into superstructures by using focused laser beams. However, as the optical energy is turned off, the inherent Brownian motion of the particles in fluid media impedes the retention and reconfiguration of such superstructures. Overcoming this fundamental limitation, we present on-demand, three-dimensional (3D) optical manipulation of colloidal particles in a phase-change solid medium made of surfactant bilayers. Unlike liquid crystal media, the lack of fluid flow …

Fungi Of The Order Mucorales Express A “Sealing-Only” Trna Ligase, Khondakar Sayef Ahammed, Ambro Van Hoof

Faculty, Staff and Student Publications

Some eukaryotic pre-tRNAs contain an intron that is removed by a dedicated set of enzymes. Intron-containing pre-tRNAs are cleaved by tRNA splicing endonuclease, followed by ligation of the two exons and release of the intron. Fungi use a "heal and seal" pathway that requires three distinct catalytic domains of the tRNA ligase enzyme, Trl1. In contrast, humans use a "direct ligation" pathway carried out by RTCB, an enzyme completely unrelated to Trl1. Because of these mechanistic differences, Trl1 has been proposed as a promising drug target for fungal infections. To validate Trl1 as a broad-spectrum drug target, we show that …

Neoadjuvant Chemotherapy Alone Or Combined With Egfr-Directed Targeted Therapy Or Anti-Pd-1 Immunotherapy For Locally Advanced Lacrimal Sac And Nasolacrimal Duct Carcinomas, Jeremy Goldfarb, Janet Fan, Luana Guimaraes De Sousa, Neal Akhave, Jeffrey Myers, Ryan Goepfert, Krish Manisundaram, Jiawei Zhao, Steven J Frank, Amy Moreno, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

Background/aims: We describe our findings in patients with locally advanced lacrimal sac and nasolacrimal duct (NLD) carcinoma who received neoadjuvant systemic therapy.

Methods: We identified patients with locally advanced primary lacrimal sac/NLD carcinoma treated with neoadjuvant systemic intravenous therapy at our institution during 2017-2019.

Results: The study included seven patients, four men and three women; the mean age was 60.4 years (range: 43-76). All patients had locally advanced disease with significant orbital soft tissue invasion with or without skull base invasion making eye-sparing surgery not feasible as an initial step. Three patients had poorly differentiated squamous cell carcinoma; two, invasive …

Ultrasound Biomicroscopy As A Novel, Potential Modality To Evaluate Anterior Segment Ophthalmic Structures During Spaceflight: An Analysis Of Current Technology, Benjamin Soares, Joshua Ong, Daniela Osteicoechea, Cihan Mehmet Kadipasaoglu, Ethan Waisberg, Prithul Sarker, Nasif Zaman, Alireza Tavakkoli, Gianmarco Vizzeri, Andrew G Lee

Faculty, Staff and Student Publications

Ocular health is currently a major concern for astronauts on current and future long-duration spaceflight missions. Spaceflight-associated neuro-ocular syndrome (SANS) is a collection of ophthalmic and neurologic findings that is one potential physiologic barrier to interplanetary spaceflight. Since its initial report in 2011, our understanding of SANS has advanced considerably, with a primary focus on posterior ocular imaging including fundus photography and optical coherence tomography. However, there may be changes to the anterior segment that have not been identified. Additional concerns to ocular health in space include corneal damage and radiation-induced cataract formation. Given these concerns, precision anterior segment imaging …

Sabr For Sarcoma Lung Metastases: Indications For Treatment And Guidance For Patient Selection, Ahsan S Farooqi, Alison K Yoder, Heather Y Lin, Dario Pasalic, Jeremy Erasmus, Sonia Betancourt, Cort Wernz, Devarati Mitra, Maria A Zarzour, Neeta Somaiah, Anthony Conley, Ravin Ratan, Andrew Livingston, Dejka M Araujo, Christina Roland, Christopher Scally, Emily Keung, Saumil N Gandhi, B Ashleigh Guadagnolo, Quynh-Nhu Nguyen, Andrew J Bishop

Faculty, Staff and Student Publications

Purpose: The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases.

Methods and materials: We performed a retrospective review of patients treated at a tertiary cancer center between 2006 and 2020. Patient disease status at the time of SABR was categorized as either oligorecurrent or oligoprogressive. The Kaplan-Meier method was used to estimate disease outcomes. Uni- and multivariable …

Phase I Study Of Oric-101, A Glucocorticoid Receptor Antagonist, In Combination With Enzalutamide In Patients With Metastatic Castration-Resistant Prostate Cancer Progressing On Enzalutamide, Wassim Abida, Andrew W Hahn, Neal Shore, Neeraj Agarwal, Paul Sieber, Matthew R Smith, Tanya Dorff, Paul Monk, Matthew Rettig, Rupal Patel, Anne Page, Maureen Duff, Rongda Xu, Jian Wang, Shravani Barkund, Aleksandr Pankov, Amber Wang, Melissa R Junttila, Pratik S Multani, Anneleen Daemen, Edna Chow Maneval, Christopher J Logothetis, Michael J Morris

Faculty, Staff and Student Publications

Purpose: Increased glucocorticoid receptor (GR) signaling is a proposed compensatory mechanism of resistance to androgen receptor (AR) inhibition in metastatic castration-resistant prostate cancer (mCRPC). ORIC-101 is a potent and selective orally-bioavailable GR antagonist.

Patients and methods: Safety, pharmacokinetic/pharmacodynamic, and antitumor activity of ORIC-101 in combination with enzalutamide were studied in patients with mCRPC progressing on enzalutamide. ORIC-101 doses ranging from 80 to 240 mg once daily were tested in combination with enzalutamide 160 mg once daily. Pharmacokinetics/pharmacodynamics was assessed after a single dose and at steady state. Disease control rate (DCR) at 12 weeks was evaluated at the recommended phase …

Toward Clinical-Grade Evaluation Of Large Language Models, Amy C Moreno, Danielle S Bitterman

Faculty, Staff and Student Publications

No abstract provided.

Clonal Dominance Defines Metastatic Dissemination In Pancreatic Cancer, I-Lin Ho, Chieh-Yuan Li, Fuchenchu Wang, Li Zhao, Jingjing Liu, Er-Yen Yen, Charles A Dyke, Rutvi Shah, Zhaoliang Liu, Ali Osman Çetin, Yanshuo Chu, Francesca Citron, Sergio Attanasio, Denise Corti, Faezeh Darbaniyan, Edoardo Del Poggetto, Sara Loponte, Jintan Liu, Melinda Soeung, Ziheng Chen, Shan Jiang, Hong Jiang, Akira Inoue, Sisi Gao, Angela Deem, Ningping Feng, Haoqiang Ying, Michael Kim, Virginia Giuliani, Giannicola Genovese, Jianhua Zhang, Andrew Futreal, Anirban Maitra, Timothy Heffernan, Linghua Wang, Kim-Anh Do, Gaetano Gargiulo, Giulio Draetta, Alessandro Carugo, Ruitao Lin, Andrea Viale

Faculty, Staff and Student Publications

Tumors represent ecosystems where subclones compete during tumor growth. While extensively investigated, a comprehensive picture of the interplay of clonal lineages during dissemination is still lacking. Using patient-derived pancreatic cancer cells, we created orthotopically implanted clonal replica tumors to trace clonal dynamics of unperturbed tumor expansion and dissemination. This model revealed the multifaceted nature of tumor growth, with rapid changes in clonal fitness leading to continuous reshuffling of tumor architecture and alternating clonal dominance as a distinct feature of cancer growth. Regarding dissemination, a large fraction of tumor lineages could be found at secondary sites each having distinctive organ growth …

Safety And Efficacy Of Ibrutinib In Combination With Rituximab And Lenalidomide In Previously Untreated Follicular And Marginal Zone Lymphoma: An Open Label, Phase 2 Study, Max J Gordon, Lei Feng, Paolo Strati, Hun Ju Lee, Fredrick B Hagemeister, Jason R Westin, Felipe Samaniego, Mario L Marques-Piubelli, Francisco Vega Vazquez, Edwin R Parra Cuentas, Luisa M Solis-Soto, Wencai Ma, Jing Wang, Linda Claret, Barbara Averill, Karina Ibanez, Luis E Fayad, Christopher R Flowers, Michael R Green, R Eric Davis, Sattva S Neelapu, Nathan H Fowler, Loretta J Nastoupil

Faculty, Staff and Student Publications

Background: Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity-rationally designed, combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with lenalidomide, rituximab, and ibrutinib (IRR) in a phase 1 study.

Methods: The authors conducted an …

Β-Actin G342d As A Cause Of Nk Cell Deficiency Impairing Lytic Synapse Termination, Abigail E Reed, Jackeline Peraza, Frederique Van Den Haak, Evelyn R Hernandez, Richard A Gibbs, Ivan K Chinn, James R Lupski, Enrica Marchi, Ran Reshef, Bachir Alobeid, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Natural killer (NK) cell deficiency (NKD) occurs when an individual’s major clinical immunodeficiency derives from abnormal NK cells and is associated with several genetic etiologies. Three categories of β actin-related diseases with over 60 ACTB (β actin) variants have previously been identified, none with a distinct NK cell phenotype. An individual with mild developmental delay, macrothrombocytopenia, susceptibility to infections, molluscum, and EBV-associated lymphoma had functional NK cell deficiency for over a decade. A de novo ACTB variant encoding G342D β actin was identified and was consistent with the individual’s developmental and platelet phenotype. This novel variant also was found to …

Label-Aware Distance Mitigates Temporal And Spatial Variability For Clustering And Visualization Of Single-Cell Gene Expression Data, Shaoheng Liang, Jinzhuang Dou, Ramiz Iqbal, Ken Chen

Faculty, Staff and Student Publications

Clustering and visualization are essential parts of single-cell gene expression data analysis. The Euclidean distance used in most distance-based methods is not optimal. The batch effect, i.e., the variability among samples gathered from different times, tissues, and patients, introduces large between-group distance and obscures the true identities of cells. To solve this problem, we introduce Label-Aware Distance (LAD), a metric using temporal/spatial locality of the batch effect to control for such factors. We validate LAD on simulated data as well as apply it to a mouse retina development dataset and a lung dataset. We also found the utility of our …

A Road Map Of Relapse In Mds After Allo-Hsct, Juan Jose Rodriguez-Sevilla, Simona Colla

Faculty, Staff and Student Publications

No abstract provided.

Cytoplasmic Genome Contributions To Domestication And Improvement Of Modern Maize, Shuai Cao, Huanhuan Zhang, Yang Liu, Yi Sun, Z Jeffrey Chen

Faculty, Staff and Student Publications

Background: Studies on maize evolution and domestication are largely limited to the nuclear genomes, and the contribution of cytoplasmic genomes to selection and domestication of modern maize remains elusive. Maize cytoplasmic genomes have been classified into fertile (NA and NB) and cytoplasmic-nuclear male-sterility (CMS-S, CMS-C, and CMS-T) groups, but their contributions to modern maize breeding have not been systematically investigated.

Results: Here we report co-selection and convergent evolution between nuclear and cytoplasmic genomes by analyzing whole genome sequencing data of 630 maize accessions modern maize and its relatives, including 24 fully assembled mitochondrial and chloroplast genomes. We show that the …

Author Correction: Hypomorphic Brca2 And Rad51c Double Mutant Mice Display Fanconi Anemia, Cancer And Polygenic Replication Stress, Karl-Heinz Tomaszowski, Sunetra Roy, Carolina Guerrero, Poojan Shukla, Caezaan Keshvani, Yue Chen, Martina Ott, Xiaogang Wu, Jianhua Zhang, Courtney D Dinardo, Detlev Schindler, Katharina Schlacher

Faculty, Staff and Student Publications

No abstract provided.

Incidence And Risk Factors Of Early Onset Vod/Sos Differ In Younger Vs Older Adults After Stem Cell Transplantation, Curtis Marcoux, Rima M Saliba, Whitney Wallis, Sajad Khazal, Dristhi Ragoonanan, Gabriela Rondon, Priti Tewari, Uday Popat, Betul Oran, Amanda Olson, Qaiser Bashir, Muzaffar Qazilbash, Amin Alousi, Chitra Hosing, Yago Nieto, Gheath Alatrash, David Marin, Katayoun Rezvani, Issa Khouri, Samer Srour, Richard Champlin, Elizabeth Shpall, Partow Kebriaei

Faculty, Staff and Student Publications

Veno-occlusive disease (VOD) is a rare but potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Although increasing awareness and modern transplant techniques have mitigated risk, the interaction of historic risk factors in the current era with posttransplant cyclophosphamide (PTCy) is unknown. We performed a retrospective single-center analysis of adult patients aged ≥18 years undergoing allo-SCT (N = 1561) using predominately PTCy as graft-versus-host disease (GVHD) prophylaxis (72%). We found a higher rate of VOD at 16.8% (20 of 119) in those aged ≤25 years compared with 3.8% (55 of 1442) in those aged >25 years, with unique predictors …

Draft Genome Sequences Of Pseudomonas Strains Zfem001–005 Isolated From The Intestine Of Larval Zebrafish Danio Rerio, Sabona B Simbassa, Justin Clark, Keiko Salazar, Anthony Maresso, Anne-Marie Krachler

Faculty, Staff and Student Publications

Here, we report the draft genome sequences of Pseudomonas strains zfem001–005, five isolates from the intestinal microbiota of healthy larval zebrafish Danio rerio at a developmental age of 7 days post fertilization. The isolates have been identified as Pseudomonas sediminis, Pseudomonas japonica, Pseudomonas otitidis, Pseudomonas sichuanensis, and Pseudomonas tohonis, respectively.

Immune Heterogeneity In Small-Cell Lung Cancer And Vulnerability To Immune Checkpoint Blockade, Barzin Y Nabet, Habib Hamidi, Myung Chang Lee, Romain Banchereau, Stefanie Morris, Leah Adler, Velimir Gayevskiy, Ahmed M Elhossiny, Minu K Srivastava, Namrata S Patil, Kiandra A Smith, Rajiv Jesudason, Caleb Chan, Patrick S Chang, Matthew Fernandez, Sandra Rost, Lisa M Mcginnis, Hartmut Koeppen, Carl M Gay, John D Minna, John V Heymach, Joseph M Chan, Charles M Rudin, Lauren A Byers, Stephen V Liu, Martin Reck, David S Shames

Faculty, Staff and Student Publications

Atezolizumab (anti-PD-L1), combined with carboplatin and etoposide (CE), is now a standard of care for extensive-stage small-cell lung cancer (ES-SCLC). A clearer understanding of therapeutically relevant SCLC subsets could identify rational combination strategies and improve outcomes. We conduct transcriptomic analyses and non-negative matrix factorization on 271 pre-treatment patient tumor samples from IMpower133 and identify four subsets with general concordance to previously reported SCLC subtypes (SCLC-A, -N, -P, and -I). Deeper investigation into the immune heterogeneity uncovers two subsets with differing neuroendocrine (NE) versus non-neuroendocrine (non-NE) phenotypes, demonstrating immune cell infiltration hallmarks. The NE tumors with low tumor-associated macrophage (TAM) but …

Nanofibrous Multidomain Peptide Hydrogels Provide T Cells A 3d, Cytocompatible Environment For Cell Expansion And Antigen-Specific Killing, Viridiana Leyva-Aranda, Shailbala Singh, Maria J Telesforo, Simon Young, Cassian Yee, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

T cells have the ability to recognize and kill specific target cells, giving therapies based on their potential for treating infection, diabetes, cancer, and other diseases. However, the advancement of T cell-based treatments has been hindered by difficulties in their ex vivo activation and expansion, the number of cells required for sustained in vivo levels, and preferential localization following systemic delivery. Biomaterials may help to overcome many of these challenges by providing a combined means of proliferation, antigen presentation, and cell localization upon delivery. In this work, we studied self-assembling Multidomain Peptides (MDPs) as scaffolds for T cell culture, activation, …