Medicine and Health Sciences Commons^™

Clinical And Dosimetric Dataset Of Time-To-Event Normal Tissue Complication Probability For Osteoradionecrosis, Natalie A West, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Renjie He, Mohamed A Naser, Katherine A Hutcheson, Abdallah S R Mohamed, Lisanne V Van Dijk, Amy C Moreno, Stephen Y Lai, Clifton D Fuller, Laia Humbert-Vidan

Faculty, Staff and Student Publications

Osteoradionecrosis of the jaw (ORNJ) is a radiation-induced late toxicity that can dramatically decrease patients' quality of life. Recent increases in survival rates of head and neck cancers associated with human papillomavirus (HPV) infection have resulted in a higher frequency of radiation-induced toxicities, particularly ORNJ. Recent work with Normal Tissue Complication Probability (NTCP) models and a Weibull Accelerated Failure Time (WAFT) model have further developed our understanding of ORNJ clinical/dosimetric risk factors and longitudinal features, respectively. In this data descriptor, 1129 head and neck cancer (HNC) patients received curative intent radiotherapy (RT) at MD Anderson Cancer Center and were followed …

An Integrated Single-Cell And Spatial Transcriptomic Atlas Of Thyroid Cancer Progression Identifies Prognostic Fibroblast Subpopulations, Matthew A Loberg, George J Xu, Sheau-Chiann Chen, Hua-Chang Chen, Claudia C Wahoski, Kailey P Caroland, Megan L Tigue, Heather A Hartmann, Jean-Nicolas Gallant, Courtney J Phifer, Andres A Ocampo, Dayle K Wang, Reilly G Fankhauser, Kirti A Karunakaran, Chia-Chin Wu, Maxime Tarabichi, Sophia M Shaddy, James L Netterville, Sarah L Rohde, Carmen C Solórzano, Lindsay A Bischoff, Naira Baregamian, Barbara A Murphy, Jennifer H Choe, Jennifer R Wang, Eric C Huang, Quanhu Sheng, Luciane T Kagohara, Elizabeth M Jaffee, Ryan H Belcher, Ken S Lau, Fei Ye, Ethan Lee, Vivian L Weiss

Faculty, Staff and Student Publications

Although well-differentiated thyroid carcinoma (WDTC) is characterized by a robust treatment response, aggressive subtypes, such as anaplastic thyroid carcinoma (ATC), remain highly lethal. To understand thyroid cancer evolution in both children and adults, we analyzed single-cell transcriptomes of 423,733 cells from 81 samples and spatially resolved key tumor and microenvironment populations across 28 tumors with spatial transcriptomics, including rare and unique composite WDTC/ATC tumors and pediatric diffuse sclerosing thyroid carcinomas. Additionally, we identified gene signatures of stromal cell populations in 5 large thyroid cancer bulk RNA-sequencing cohorts. Through this multi-institutional effort, we defined a population of POSTN+ myofibroblast cancer-associated fibroblasts …

Defining Rna Oligonucleotides That Reverse Deleterious Phase Transitions Of Rna-Binding Proteins With Prion-Like Domains., Lin Guo, Jacob Mann, Jocelyn Mauna, Katie Copley, Hejia Wang, Jack Rubien, Cristian Bergmann, Jenny Carey, Jessica Merjane, Marilyn Ngo, Jiazhen Xu, Hana Odeh, Jiabei Lin, Bo Lim Lee, Laura Ganser, Emma Robinson, Kevin Kim, Anastasia Murthy, Tapas Paul, Bede Portz, Amanda Gleixner, Zamia Diaz, Ashleigh Smirnov, George Padilla, Ellen Lavorando, Carolann Espy, Yulei Shang, Eric Huang, Alessandra Chesi, Nicolas Fawzi, Sua Myong, Christopher Donnelly, James Shorter

Department of Biochemistry and Molecular Biology Faculty Papers

RNA-binding proteins (RBPs) with prion-like domains (PrLDs), such as FUS and TDP-43, condense into functional liquids, which can transform into pathological fibrils that underpin fatal neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). Here, we define short RNAs that prevent FUS fibrillization by promoting liquid phases and distinct short RNAs that prevent and reverse FUS condensation and fibrillization. These activities require interactions with multiple RNA-binding domains of FUS and are encoded by RNA sequence, length, and structure. We define a short RNA that dissolves cytoplasmic FUS aggregates, restores nuclear FUS, and mitigates FUS toxicity in optogenetic models and ALS …

Multi-Institutional Normal Tissue Complication Probability (Ntcp) Prediction Model For Mandibular Osteoradionecrosis: Results From The Predmorn Study, Laia Humbert-Vidan, Christian R Hansen, Steven Petit, Carles Muñoz-Montplet, Katrina Hueniken, Abdallah S R Mohamed, Deborah P Saunders, Vinod Patel, Gerda M Verduijn, Wilma D Heemsbergen, Arjen Van Der Schaaf, Max Witjes, Suzanne P M De Vette, Mohammad Moharrami, Abdul A Khan, Jordi Marruecos Querol, Irene Oliveras Cancio, Mike Oliver, Peter Reich, Stacey A Santi, Andrew G Pearce, Stephen Y Lai, Andrew P King, Ali Hosni, Andrew J Hope, Erin E Watson, Johannes A Langendijk, Jørgen Johansen, Amy C Moreno, Clifton D Fuller, Lisanne V Van Dijk, Teresa Guerrero Urbano

Faculty, Staff and Student Publications

Purpose: Mandibular osteoradionecrosis (ORN) is a severe late complication affecting patients with head and neck cancer (HNC) treated with radiation therapy (RT) that significantly impacts patients' quality of life and can require costly interventions. Although radiation dose is a key factor, other clinical and demographic risk factors also influence ORN development. Previous predictive models have primarily been single-institutional, limiting their generalizability. In this first analysis from the PREDMORN Consortium, we have aimed to reproduce existing statistical association and modeling analyses on the largest and most diverse mandibular ORN cohort worldwide to allow comparison with previous studies.

Methods and materials: This …

Disparities In Cardiovascular Disease Burden Among Black And Hispanic Survivors Of Adolescent And Young Adult (Aya) Cancer, Tori Tonn, Maanvi Thawani, Margaret Mazer, Greg Aune, Debra Eshelman-Kent, Karen Albritton, Efstratios Koutroumpakis, Michael E Roth, Michelle A T Hildebrandt

Faculty, Staff and Student Publications

Background: Despite significant improvements in long-term survival outcomes for adolescents and young adults (AYAs) with cancer, common treatment regimens often pose substantial risks to the cardiovascular health of this survivor population. Differences in cardiovascular events by race/ethnicity and genetic ancestry within this at risk population remain unclear.

Methods: In this study, we investigated adverse cardiovascular outcomes in a diverse population of AYA cancer survivors (n = 346) treated at MD Anderson Cancer Center for Hodgkin lymphoma and sarcoma. Analysis was conducted by self-identified race/ethnicity and by genetic ancestry.

Results: Black and Hispanic survivors demonstrated the greatest burden of poor …

Thermodynamic Stability Modulates Chaperone-Mediated Disaggregation Of Α-Synuclein Fibrils, Celia Fricke, Antonin Kunka, Rasmus K Norrild, Shuangyan Wang, Thi Lieu Dang, Jonas Folke, Mohammad Shahnawaz, Claudio Soto, Susana Aznar, Anne S Wentink, Bernd Bukau, Alexander K Buell

Faculty, Staff and Student Publications

Aggregation of the intrinsically disordered protein alpha-synuclein into amyloid fibrils and their subsequent intracellular accumulation are hallmark features of several neurodegenerative disorders, including Parkinson's disease, for which no curative treatments currently exist. In this study, we investigate the relationship between fibril morphology, thermodynamic stability, and susceptibility to disaggregation by the human chaperone system comprising HSP70, DNAJB1, and Apg2. By varying assembly conditions and incubation times, we generated alpha-synuclein fibrils with diverse morphological and biochemical properties, including a broad range of thermodynamic stabilities, which we quantified using a chemical depolymerization assay. The chaperone system effectively disaggregated three of the four fibril …

Characterization Of Inflammatory Pseudotumors In A Large Animal Model Of Liver Cancer, Erik N K Cressman, Samantha Hicks, Natalie W Fowlkes, Danielle L Stolley, Maria Sophia Stenkamp

Faculty, Staff and Student Publications

Background: The development of relevant and robust large animal models of hepatocellular carcinoma is needed to test new therapeutic strategies for this disease. Transgenic approaches hold promise in addressing this complex problem. One such model, the Oncopig, has been reported to develop tumors of up to 4 cm in diameter within 7-14 days at sites of in situ vector inoculation. However, the resulting lesions reportedly contained an extensive inflammatory component that has not been evaluated in detail.

Methods: Herein, we describe our results from multiparametric characterization of the lesions generated using liver biopsy cores incubated in vector solution and replaced …

Loss Of Kdm6a-Mediated Genomic Instability And Metabolic Reprogramming Regulates Response To Therapeutic Perturbations In Bladder Cancer, Pratishtha Singh, Ranit D'Rozario, Bidisha Chakraborty, Swadhin Meher, Deblina Raychaudhuri, Aminah J Tannir, Yang Li, Anurag Majumdar, Jessalyn Hawkins, Yun Xiong, Philip Lorenzi, Padmanee Sharma, Kadir Akdemir, Patrick Pilie, Abhinav K Jain, Byron Hing Lung Lee, Sangeeta Goswami

Faculty, Staff and Student Publications

Mutations in epigenetic regulators are common in bladder cancer, yet their impact on therapeutic responses remains unclear. Here, we identify that loss-of-function mutations in KDM6A, a histone demethylase altered in about 26% of advanced bladder cancers, are associated with poor survival after cisplatin chemotherapy, whereas they correlate with improved outcomes with anti-PD-1 therapy. Using CRISPR-Cas9-engineered murine and human bladder cancer models, we show that KDM6A deficiency increases formation of extrachromosomal circular DNA carrying chemoresistance loci, promoting cisplatin resistance. In parallel, KDM6A loss impairs DNA repair and rewires tumor metabolism, reducing glycolysis and lactate output. This metabolic shift diminishes histone lactylation …

3d Reconstruction Of Spatial Transcriptomics With Spatial Pattern Enhanced Graph Convolutional Neural Network, Chen Tang, Yuansheng Zhou, Xue Xiao, Lei Dong, Lei Yu, Qiwei Li, Guanghua Xiao, Lin Xu

Faculty, Staff and Student Publications

Spatially resolved transcriptomics (SRT) is a promising new technology that enables simultaneous analysis of gene expression and spatial information for biomedical research. However, the existing statistical and deep learning algorithms used for analyzing SRT data rely solely on two-dimensional (2D) spatial coordinates, which limits their ability to accurately identify spatial domains, spatially variable genes (SVGs), cell-to-cell communications, and developmental trajectories in a three-dimensional (3D) spatial manner. To address these limitations, we introduced Spa3D, which utilized the anti-leakage Fourier transform and graph convolutional neural network model to reconstruct 3D-based spatial structures from multiple 2D SRT slices. We demonstrate that Spa3D is …

The Role Of Extracellular Vesicles As Diagnostic Tools In Gut-Brain Axis Disorders, Patricia Marçal Da Costa, Paulo Iury Gomes Nunes, Gabriella Cunha Vieira Ciurleo, José Wagner Leonel Tavares Junior, Pedro Braga Neto, Ludmila Belayev, Reinaldo Barreto Oriá

School of Graduate Studies Faculty Publications

The gut–brain axis represents a dynamic two-way signaling network whose dysregulation has been implicated in a wide range of neurogastrointestinal disorders. In this context, extracellular vesicles (EVs) have emerged as critical mediators of intercellular signaling and as promising non-invasive biomarkers. Derived from host and microbial cells, EVs carry bioactive cargo—including proteins, lipids, nucleic acids, and metabolites—that reflect the physiological or pathological state of their cells of origin. Their ability to cross biological barriers, such as the blood–brain barrier, underscores their potential for diagnosing and monitoring gut–brain axis dysfunctions. In this mini-review, we integrate microbial and brain-derived EVs within the framework …

Defective Dna Damage Response Is A Targetable Therapeutic Vulnerability In Esr1 Mutant Breast Cancer, Sarah K Herzog, Jessica H Stevens, Guowei Gu, Sandra L Grimm, Kloma Cardoza, Autumn G M Hawkins, Hangqing Lin, Daniela Ramos, Amanda R Beyer, David G Edwards, Derek Dustin, Harry J Yang, Nicole Liang, Ashfia F Khan, Tasneem Bawa-Khalfe, Daniel J Mcgrail, Shiaw-Yih Lin, Cristian Coarfa, Suzanne A W Fuqua

Faculty, Staff and Student Publications

ESR1 mutations are the leading cause of endocrine therapy resistance and progression in ER-positive metastatic breast cancer. ESR1 mutations are detected in ~50% of metastatic breast cancer patients, and identification of effective targeted therapeutics are critically needed. Here, we identified enrichment of dysregulated replication stress and DNA damage responses in multiple ESR1 mutant models. Targeting the replication stress response utilizing checkpoint inhibition in combination with PARP inhibition synergistically suppressed growth, induced cell cycle arrest, and attenuated DNA replication. PARP inhibition blocked metastatic dissemination in vivo and reduced both PARP1 and ER-regulated protein expression. PARP trapping by olaparib treatment with or …

Factors Affecting The Colony Count Of Oral Candida Albicans Of Electronic Cigarette Users Among Young Adults In Dasmariñas, Cavite, Kyla Marie C. Resuma, Rendell B. Rovelo, Martella Ingrid A. Sanchez, Christine Joy R. Sobiono, Michaela Marie N. Tena, Gabriel C. Villota

The Lasallian Journal of Health

Electronic cigarettes (e-cigarettes) emerged and were marketed as a more viable alternative to traditional tobacco smoking, especially among the youth. While there is insufficient evidence clearly explaining the effects of e-cigarette use on human health, recent literature has shone light on its various adverse effects on the body, particularly on oral health and its possible contribution to oral microbial dysbiosis. This study explored the potential factors that may have affected the colony counts of oral Candida albicans—the causative agent of thrush. The study participants (N = 40) comprised 22 male and 18 female e-cigarette users aged 18 to 22 …

Association Between Ultraprocessed Food Consumption And Cardiovascular Disease Risk: Mesa (Multiethnic Study Of Atherosclerosis), Amier Haidar, Rishi Rikhi, Karol E Watson, Alexis C Wood, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ultraprocessed foods (UPFs) have been linked to adverse cardiometabolic outcomes and increased atherosclerotic cardiovascular disease (CVD) (ASCVD) risk. However, prior research has largely focused on homogenous populations, lacking racial and ethnic diversity.

Objectives: The objectives are to examine the longitudinal relationship between UPF consumption and ASCVD risk and to investigate whether these associations differ by race/ethnicity, sex, or socioeconomic status.

Methods: The MESA (Multiethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 U.S. adults aged 45 to 84 years, without clinically apparent CVD. UPF consumption was classified according to the Nova classification system. Multivariable cox proportional hazards …

N-Palmitoyl Glutamine Is A Candidate Mediator Of Cardiorespiratory Fitness, Jeremy M Robbins, Mark Benson, Anthony R P Verkerke, Gaurav Tiwari, Shuliang Deng, Prashant Rao, Usman A Tahir, Julian Avila-Pacheco, Xu Shi, Yuntian Guan, Foje-Geh Tendoh, Jacob L Barber, Patricia E Miller, Andrew S Perry, Michael E Hall, Alexis C Wood, Kent D Taylor, Wendy S Post, Stephen S Rich, Matthew Nayor, James G Wilson, Gregory D Lewis, Ravi V Shah, Jerome I Rotter, Scott A Summers, Laura M Raffield, Shingo Kajimura, Claude Bouchard, Clary B Clish, Mark A Sarzynski, Robert E Gerszten

Children’s Nutrition Research Center Staff Publications

Background: Cardiorespiratory fitness is an integrative measure of cardiometabolic health and predictor of survival, yet little is known about its molecular underpinnings. Small molecule metabolites and lipids are increasingly recognized as exercise-stimulated signaling molecules and candidate molecular transducers of cardiorespiratory fitness.

Methods: We performed nontargeted liquid chromatography mass spectrometry-based plasma metabolomics in 654 participants (mean age, 35 years; 55% women) from the HERITAGE Family Study (Health, Risk Factors, Exercise Training, and Genetics) who had cardiorespiratory fitness (maximal oxygen uptake [VO2max]) measured by cardiopulmonary exercise testing and underwent 20 weeks of supervised endurance training. Metabolite-VO2max relationships were assessed using linear regression …

Knockrbp: An Integrated Multi-Omics Database Of Functional Perturbation Profiles For Rna-Binding Proteins, Mengyuan Yang, Jiawei Li, Jiajia Liu, Xingzheng Lu, Xiaobo Zhou, Yungang Xu

Faculty, Staff and Student Publications

RNA-binding proteins (RBPs) regulate diverse post-transcriptional processes, yet their functional impacts across multiple molecular layers remain incompletely characterized. KnockRBP (https://knockrbp.xu-bioinfo.com) is presented as a comprehensive, multi-omics database systematically cataloging regulatory changes resulting from genetic perturbation of RBPs. The resource integrates 1453 datasets from GEO, ENA, and ENCORE, encompassing RNA-seq, Ribo-seq, microRNA (miRNA)-seq, and 3'RACE-seq across 639 RBPs, 182 cell lines, and 61 diseases. Regulatory outcomes covered include alternative splicing, alternative polyadenylation, RNA editing, transcript abundance, translation efficiency, and miRNA expression, with all events processed through standardized analytical pipelines and annotated with open reading frame consequences, predicted loss-of-function impacts, and established …

Inhibition Of Gpx4 Induces The Death Of P53-Mutant Triple-Negative Breast Cancer Cells, William M Tahaney, Amanda Lanier, Jing Qian, Cassandra L Moyer, Nghi Nguyen, Yanxia Ma, Jamal Hill, Reid T Powell, Clifford C Stephan, Peter J A Davies, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of tumor protein 53 (TP53) mutation and with limited targeted therapies. Despite being clinically advantageous, direct targeting of mutant TP53 has been challenging. Therefore, we hypothesized that p53-mutant TNBC cells rely upon other potentially targetable survival pathways.

Methods: In vitro and in silico screens were used to identify drugs that induced preferential death in TP53-mutant cells. The effect of the ferroptosis inducer ML-162 was tested both in vitro and in vivo and the mechanism of cell death following ML-162 treatment or GPX4 knockout was …

Peripheral Nerve Injury Reduces Macrophage Efferocytosis To Facilitate Neuropathic Pain, Vipul K Pandey, Tusar K Acharya, Kendal F Willcox, Sandeep Dembla, Ajeena Ramanujan, Anamaria R Grieco, Younus A Zuberi, Rajasekaran Mahalingam, Andrew J Shepherd, Cobi J Heijnen, Peter M Grace

Faculty, Staff and Student Publications

For reasons not fully understood, proresolving immune processes sometimes fail to engage after peripheral nerve injury (PNI), leading to enhanced neuropathic pain and inflammation. Here, we implicate reduced efferocytosis due to proteolytic cleavage of surface MER tyrosine kinase (MERTK) from macrophages at the site of PNI. After PNI, the proportion of macrophages expressing MERTK progressively decreased, while soluble (cleaved) MER increased. Using male and female knock-in mice encoding cleavage-resistant Mertk, we demonstrated that cleavage of MERTK from macrophages at the PNI site led to exaggerated pain-related behaviors. PNI-induced hyperactivity of TRPV1+ sensory neurons and damage to myelin and myelinated …

Spatial2gwas: A Database For Linking Spatial Transcriptomic Regions With Gwas Traits, Xi Hu, Aoqi Wang, Huan Yu, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Spatial heterogeneity of gene expression within tissue regions has a critical influence on biological functions, thereby affecting disease pathogenesis. However, systematic associations between spatially resolved transcriptomes and phenotypes, especially in complex diseases, remain underexplored. Here, we developed spatial2GWAS (http://www.spatial2gwas.cn), a comprehensive resource linking spatial transcriptomic (ST) regions with GWAS traits. In the database, we collected 1196 ST slices (human and mouse) from five technologies and 812 GWAS traits spanning 18 phenotype categories and identified 29 701 ST slice-GWAS trait pairs containing 47 492 significant regions. Functional analyses reveal distinct patterns of cell type composition, gene expression, GO/KEGG pathway activation, and …

Correction: Sadagopan Et Al Reduced Computed Tomography Scan Speed Improves Alignment Errors For Patients Undergoing Thoracic Stereotactic Body Radiation Therapy, Ramaswamy Sadagopan, Rachael M Martin-Paulpeter, Christopher R Peeler, Xiaochun Wang, Paige Nitsch, Julianne M Pollard-Larkin

Faculty, Staff and Student Publications

In the original publication [...].

Modality-Agnostic, Patient-Specific Digital Twins Modeling Temporally Varying Digestive Motion, Jorge Tapias Gomez, Nishant Nadkarni, Lando S Bosma, Jue Jiang, Ergys D Subashi, William P Segars, James M Balter, Mert R Sabuncu, Neelam Tyagi, Harini Veeraraghavan

Faculty, Staff and Student Publications

No abstract provided.

Prevalence And Characteristics Of Prescription Errors In Community Pharmacies In Mbarara City, South Western Uganda, Tadele Mekuriya Yadesa, Ashaba Comfort, Komukyeya Esther Marvel, Namakula Angela, Tikolu Hope Nancy, Narayana Goruntla, Sarad Pawar Naik Bukke, Bontu Aschale Abebe, Efrata Ashuro Shegena

AUIQ Complementary Biological System

A prescription error is a failure in the prescription writing process that results in a wrong instruction about one or more of the standard features of a prescription. Most adverse drug events are preventable through promoting rational drug use; primarily by mitigating the outstanding high burden of prescribing errors. The main aim of this study is to assess the prevalence and characteristics of prescription errors in the community pharmacies in Mbarara, Uganda. A cross-sectional study was conducted in selected community pharmacies in Mbarara City, South Western Uganda. Consecutive sampling of all prescriptions availed at the selected pharmacies was conducted until …

Conclusions Are Not Supported By The Published Statistical Analysis Comment On López-Toledo Et Al Flaxseed Improves Glucose And Lipid Metabolism In Mexican Subjects With Type 2 Diabetes: A Parallel Randomized Clinical Trial, Robert W Spitz, Deependra K Thapa, Thirupathi Reddy Mokalla, Wasiuddin Najam, Andrew W Brown, David B Allison

Children’s Nutrition Research Center Staff Publications

López-Toledo et al [...].

A Prognostic Matrix Gene Expression Signature Defines Functional Glioblastoma Phenotypes And Niches, Monika Vishnoi, Zeynep Dereli, Zheng Yin, Elisabeth K Kong, Meric Kinali, Kisan Thapa, Ozgun Babur, Kyuson Yun, Nourhan Abdelfattah, Xubin Li, Behnaz Bozorgui, Mary C Farach-Carson, Robert C Rostomily, Anil Korkut

Faculty, Staff and Student Publications

Interactions among tumor, immune, and vascular niches play major roles in glioblastoma (GBM) malignancy and treatment responses. The composition and heterogeneity of extracellular core matrix proteins (CMPs) that mediate such interactions are not well understood. Here, we present an analysis of the clinical relevance of CMP expression in GBM at bulk, single-cell, and spatial anatomical resolution. We show that CMP enrichment is associated with worse patient survival, specific driver oncogenic alterations, mesenchymal state, pro-tumor immune infiltration, and immune checkpoint expression. Matrisome expression is enriched in vascular and leading edge/infiltrative niches that are known to harbor glioma stem cells. Finally, we …

Precision Targeting Of Sting: Challenges, Innovations, And Clinical Outlook For Cancer Therapy, Jiaqi Shi, Yingying Zhang, Na Zhao, Ekihiro Seki, Li Ma, Gordana Kocic, Xiaobo Li, Janoš Terzić, Tongsen Zheng

Faculty, Staff and Student Publications

The stimulator of interferon genes (STING) pathway plays a crucial role in immune responses and has emerged as a compelling target in cancer therapy. Despite promising preclinical studies, clinical trials of STING agonists have largely failed to deliver durable efficacy, with no agents progressing to phase III trials. This review examines the biological, pharmacological, and clinical barriers limiting STING pathway activation in cancer treatment. We discuss the inherent limitations of STING agonists as well as host-related resistance driven by tumor heterogeneity, immune suppression, and chronic STING activation. Mechanisms of acquired resistance, such as immune checkpoint upregulation and suppression of effector …

International Guidelines On The Diagnosis And Treatment Of Nut Carcinoma, Yu Zhang, Qi Zhang, Yue Hao, Jia Luo, Yingshi Piao, Wenxian Wang, Zhengbo Song, Ziming Li, Luka Brcic, Aijun Liu, Jinpu Yu, Yasuhiro Tsutani, Wenzhao Zhong, Wenfeng Fang, Zhijie Wang, Shengxiang Ren, Athanasios G Papavassiliou, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Ayten Kayi Cangir, Anwen Liu, Wen Li, Filippo Lococo, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfeng Min, Helmut Popper, Yu Chen, Jingping Yuan, Feng Wang, Zhansheng Jiang, Gen Lin, Long Huang, Xingxiang Pu, Rongbo Lin, Kalevi Kairemo, Weifeng Liu, Chuangzhou Rao, Dongqing Lv, Zongyang Yu, Ashrafian Leanne, Xiaoyan Li, Chuanhao Tang, Hifzur R Siddique, Chengzhi Zhou, Junping Zhang, Junli Xue, Vishal Shelat, Hui Guo, Qian Chu, Rui Meng, Fatemeh Ardeshir, Jingxun Wu, Rui Zhang, Jin Zhou, Robert A Kratzke, Zhengfei Zhu, Yongheng Li, Hong Qiu, Fan Xia, Fiorella Calabrese, Yang Xia, Alessandro Wasum Mariani, Yuanyuan Lu, Xiaofeng Chen, Mark A Klein, Rui Ge, Enyong Dai, Axel H Schönthal, Yu Han, Zhenying Guo, Jian Zhang, Yinghua Ji, Xianbin Liang, Hongmei Zhang, Xuelei Ma, Marco Chiappetta, Xuewen Liu, Francoise Galateau Salle, Yu Yao, Malgorzata Szolkowska, Weiwei Pan, Fei Pang, Fan Wu, Stefan B Watzka, Liping Wang, Youcai Zhu, Li Lin, Aparna Sharma, Jianfei Tu, Xinqing Lin, Jing Cai, Ling Xu, Jisheng Li, Xiaodong Jiao, Kainan Li, Marjorie G Zauderer, Jia Wei, Huijing Feng, Lin Wang, Yingying Du, Wang Yao, Elizabeth Dudnik, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jianhui Huang, Yue Feng, Yinbin Zhang, Binbin Song, Wenfeng Li, Jianfei Fu, Marina K Baine, Pingli Sun, Hong Wang, Mingxiang Ye, Dong Wang, Zhaofeng Wang, Jing Wu, Yunyun Yang, Yuan Fang, Zhen Wang, Bin Wan, Donglai Lv, Huafei Chen, Shengjie Yang, Jing Kang, Jiatao Zhang, Chao Zhang, Lin Shi, Yina Wang, Mohamed Emam Sobeih, Bihui Li, Bin Lian, Lili Mao, Zhang Zhang, Ke Wang, Zhongwu Li, Zhefeng Liu, Nong Yang, Lin Wu, Xiaobing Chen, Gu Jin, Miao Li, Guansong Wang, Thomas U Marron, Jiandong Wang, Sanjay Popat, Meiyu Fang, Yong Fang, Daniel Mansilla, Yuan Li, Xiaojia Wang, Jing Chen, Yiping Zhang, Xixu Zhu, Yi Shen, Shenglin Ma, Aaron S Mansfield, Biyun Wang, Lu Si, Anja C Roden, Bjørn H Grønberg, Yong Song, Geoffrey I Shapiro, Christopher A French, Yuanzhi Lu, Qian Wang, Chunwei Xu

Faculty, Staff and Student Publications

Nuclear protein in testis (NUT) carcinoma (NC) represents a rare, clinically aggressive cancer defined by pathognomonic NUT Midline Carcinoma Family Member 1 (NUTM1) gene fusions, with bromodomain and extraterminal domain (BET) protein 4 (BRD4)-NUTM1 being the predominant oncogenic driver. Since its description in 1991, gradual advances have clarified the pathologic mechanisms of NC and its diagnostic methods; however, NC treatment remains a significant challenge. Moreover, diagnostic and treatment approaches for this cancer require further validation and standardization. These guidelines were developed by the Chinese Alliance of Research for NC (ChARN) based on current evidence in …

Celltra: Aligning Cell Names With Gene Expression Via A Pathway-Informed Transformer, Zhao Li, Zaiyi Zheng, Rongbin Li, Wenbo Chen, Yuntao Yang, Meer A Ali, Jundong Li, W Jim Zheng

Faculty, Staff and Student Publications

Motivation: Single-cell RNA sequencing (scRNA-Seq) technology enables detailed exploration of gene expression at the individual cell level, crucial for annotating cell types and understanding cellular diversity. Traditional methods for cell type annotation often rely on marker genes and manual labeling, posing challenges due to low data quality and incomplete reference datasets.

Results: We developed CeLLTra, a novel contrastive learning framework that leverages a Transformer-based model integrating biological pathway information to group genes into super tokens, effectively capturing comprehensive gene expression from scRNA-Seq data. By combining this pathway-informed Transformer with a pretrained domain-specific language model, CeLLTra accurately aligns cell-type annotations with …

Anti-Csf-1r Therapy With Combined Immuno-Chemotherapy Coordinate An Adaptive Immune Response To Eliminate Macrophage Enriched Triple Negative Breast Cancers, Diego A Pedroza, Xueying Yuan, Fengshuo Liu, Hilda L Chan, Christina Zhang, William Bowie, Alex J Smith, Sebastian J Calderon, Nadia Lieu, Weiguo Wu, Paul Porter, Poonam Sarkar, Na Zhao, Constanze V Oehler, Ondrej Peller, M Waleed Gaber, Qian Zhu, Charles M Perou, Xiang H-F Zhang, Jeffrey M Rosen

Faculty, Staff and Students Publications

Women diagnosed with metastatic triple negative breast cancer (mTNBC) have limited treatment options, are more prone to develop resistance and are associated with high mortality. A cold tumor immune microenvironment (TIME) characterized by low T cells and high tumor associated macrophages (TAMs) in mTNBC is associated with the failure of standard-of-care chemotherapy and immune checkpoint blockade (ICB) treatment. We demonstrate that the combination of immunomodulatory low-dose Cyclophosphamide (CTX) coupled with anti-CSF-1R antibody targeted therapy (SNDX-ms6352) and anti-PD-1 (ICB), was highly effective against aggressive metastatic Trp53 null TNBC transplantable syngeneic models that present with high macrophage infiltration. Mechanistically, CSF-1R inhibition along …

A Probabilistic Modeling Analysis Of The Longitudinal Immune Response To Infection And Vaccination Across Demographic Groups And Pulmonary Symptoms, James O'Hanlon, Kaitlyn Sullivan, Lyndsey M. Muehling, Glenda Canderan, Jie Sun, Judith A. Woodfolk, Jeffrey M. Wilson, Rayanne A. Luke

Spora: A Journal of Biomathematics

Antibody and cytokine kinetics describe the dynamic response to immune events such as infection and vaccination. These dynamics are not fully understood, and mathematical characterization may help explain variability across demographic groups and pulmonary symptoms post-acute infection. We fit time-dependent probability models to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) data to obtain distributions of longitudinal antibody response and cytokine values. To assess differences between groups, an overlap metric is applied to the modeled response curves. Our antibody models suggest significant differences between male and female populations and demonstrate deficient antibody responses of less-healthy groups such as smokers. Our cytokine …

Sheep Umbilical Cord Mesenchymal Stem Cells: Biological Characteristics, Ethical Considerations, And Translational Applications, Hasan M. Agha, Mohammed A. Abdalqader, Oh Chin Kin Michelle, Sabaa M. Agha, Jantson Hoh, Abdulmutalib Alabeed Allaq, Amjad Abdulhadi Mohammed, Muneer Mohammed Saleh Alsayadi

AUIQ Complementary Biological System

Mesenchymal stem cells (MSCs) are widely used in regenerative medicine due to their self-renewal capacity, multilineage differentiation potential, and paracrine activity. Limitations associated with the sourcing and scalability of human MSCs have increased interest in xenogeneic alternatives, particularly sheep umbilical cord–derived MSCs (sUC-MSCs). These cells display high proliferative capacity, stable karyotypes, and a typical MSC immunophenotype (CD44, CD73, CD90, CD105), with low basal immunogenicity. sUC-MSCs exhibit osteogenic, chondrogenic, and adipogenic differentiation potential and secrete angiogenic and immunomodulatory factors, including VEGF, HGF, IGF-1, TGF-β, and IL-10. Owing to their biological similarities to human MSCs and accessibility from perinatal tissue, …

Circadian-Shaped Immune Variability Predicts Infection Outcome, Jonathan Lalsiamthara, Mariko Locke, Alejandro Aballay

Faculty, Staff and Student Publications

Disease risk and severity are influenced by genetics, epigenetics, and environmental factors. However, immune responses vary even among genetically similar or related individuals, shaped by inherited and noninherited factors. Using Caenorhabditis elegans, we found that pathogen susceptibility can be predicted by preinfection biomarkers. Individuals with high-basal expression of irg-5, an infection response gene regulated by the p38 mitogen-activated protein kinase-1 (PMK-1) pathway, were more susceptible to Pseudomonas aeruginosa infection. A genome-wide screen identified the myeloid ecotropic viral integration site-1 (MEIS) homeobox protein UNC-62 as a regulator of irg-5 expression, acting through PMK-1 and GATA binding erythroid-like transcription factor …