Digital Commons Network^™

A Comparison Between Carlin And Dna Typewriter In Crispr-Mediated Lineage Tracing, Fengshuo Liu, Xiang Zhang, Yipeng Yang

Faculty, Staff and Students Publications

Background: CARLIN and DNA Typewriter are two major breakthroughs in CRISPR-based lineage tracing technology. It is essential to understand the potential and performance of these methods in lineage tracing, which provides important guidance on experimental design.

Results: In this study, we systematically compare these two strategies using a unified stochastic simulation framework with known ground-truth lineages. By explicitly modeling CRISPR editing dynamics, barcode evolution, and cell division processes, the framework enables quantitative benchmarking of lineage reconstruction accuracy across diverse experimental parameter regimes. Both methods are evaluated using multiple accuracy metrics, including Robinson-Foulds accuracy and triplet accuracy, allowing a comprehensive assessment …

Toxitarget: A Multi-Omics Database For Toxicant-Responsive Molecular Targets, Ravindra Kumar, Tianyi Fu, Prashant Kumar Kuntala, Benpeng Miao, Shuhua Fu, Daofeng Li, Frederick L Tyson, Marisa S Bartolomei, Cheryl L Walker, Ting Wang, Bo A Zhang

Faculty, Staff and Students Publications

Environmental toxicant exposures can induce widespread alterations in both the transcriptome and epigenome of mammals, and directly contribute to the increased risk of various diseases, including cardiovascular disorders, cancer, and neurological disorders. To evaluate how early-life toxicants produce long-term impacts on the transcriptome and epigenome in mice, the Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription II (TaRGET II) Consortium generated a landmark resource comprising 3607 multi-omics datasets from longitudinal studies in mice. The molecular changes in responding to distinct environmental toxicants, including arsenic (As), lead (Pb), bisphenol A (BPA), tributyltin (TBT), di-2-ethylhexyl phthalate (DEHP), dioxin (TCDD), …

Icam1high Neutrophils Sculpt Tumor Evolution And Metastasis Through Symbiotic Adhesion And Reverse Migration, Ling Wu, Zhan Xu, Jun Wang, Fengshuo Liu, Yunfeng Ding, Yang Gao, Siyue Wang, Jun Liu, Hilda L Chan, Weiguo Wu, Yi-Hsuan Wu, Liqun Yu, Xiaoxin Hao, Xuan Li, David G Edwards, Cher Sha, Tobie D Lee, Nan Guan, Sergio Aguirre, Luis Becerra-Dominguez, Dane Hoffman, Xiang Chen, Charlotte Helena Rivas, Xiaoyuan G Yan, Igor L Bado, Weijie Zhang, Qian Zhu, Arun Sreekumar, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Neutrophils are a prominent component of the tumor microenvironment that can have both pro- and anti-tumor functions. By analyzing neutrophils across different human cancers, we revealed an ICAM1high subset enriched in the tumor microenvironment, which were also observed in murine triple negative breast cancer (TNBC) models. ICAM1high neutrophils exhibited an enhanced capacity for cell-cell adhesion specifically with tumor cells retaining epithelial features, and this adhesion conferred mutual advantages to both cell types. In contrast, cancer cells with mesenchymal-like phenotypes were vulnerable to neutrophil-mediated cytotoxicity due to decreased cell adhesion and elastase resistance. These opposite effects drove tumor evolution toward a …

Panda-Plus-Bench: A Clinical Benchmark For Evaluating The Robustness Of Ai Foundation Models In Prostate Cancer Diagnosis, Joshua L. Ebbert, Dennis Della Corte

Faculty Publications

Artificial intelligence foundation models are increasingly deployed for prostate cancer Gleason grading, where GP3/GP4 distinction directly impacts treatment decisions (active surveillance vs. intervention). However, these models may achieve high validation accuracy by learning specimen-specific artifacts rather than generalizable biological features, limiting real-world clinical utility. We introduce PANDA-PLUS-Bench, a curated benchmark dataset derived from expertly annotated prostate biopsies designed specifically to quantify this failure mode. The benchmark comprises nine carefully selected whole slide images from nine unique patients containing diverse Gleason patterns, with non-overlapping tissue patches extracted at both 512 × 512 and 224 × 224-pixel resolutions across eight augmentation conditions. …

Unbiased Niche Labeling Maps Immune-Excluded Niche In Bone Metastasis, Zhan Xu, Fengshuo Liu, Yunfeng Ding, Tianhong Pan, Yi-Hsuan Wu, Yujiao Han, Jun Liu, Igor L Bado, Weijie Zhang, Ling Wu, Yang Gao, Xiaoxin Hao, Liqun Yu, Xuan Li, David G Edwards, Hilda L Chan, Sergio Aguirre, Michael Warren Dieffenbach, Elina Chen, Siyue Wang, Yichao Shen, Dane Hoffman, Luis Becerra Dominguez, Charlotte Helena Rivas, Xiang Chen, Hai Wang, Yibin Kang, Zbigniew Gugala, Robert L Satcher, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastatic cancer cell fate is shaped by the local microenvironment niches. To unbiasedly define the cellular and molecular features of metastatic niches, we developed sortase A-based microenvironment niche tagging (SAMENT), which selectively labels cells encountered by cancer cells during metastasis. Applying SAMENT across multiple cancer models and target organs revealed shared niche features, including macrophage enrichment and T cell depletion, alongside marked organ-specific phenotype heterogeneity in niche macrophages. In bone, metastatic niches are enriched for macrophages expressing estrogen receptor alpha (ERα) with active ERα signaling. Conditional deletion of Esr1 in macrophages significantly impaired bone colonization by enabling T cell infiltration. …

The 2026 Fifa World Cup: Communicable Disease Risks And Advice For Visitors To Canada, The United States, And Mexico, Alfonso J Rodriguez-Morales, Ivan Arturo Rodríguez-Sabogal, Beatriz Elena Porras-Pedroza, Álvaro A Faccini-Martínez, Daniel Grisales-Nieto, Florencia Escarrá, Pasesa Pascuala Quispe-Torrez, Francisco Javier Membrillo, Tomás Orduna, Susana Lloveras, Tânia S S Chaves, Miguel M Cabada, Cecilia Perret, René Echavarría, Ana F Ribeiro, Melinda Tanabe, Fernando Bazzino, Maximiliano Ramirez, Baruch Diaz, Karen Mirna Loro Morejón, Karen Daly, Reinaldo Rosas, Maria Belen Lopez, Cristina Miranda, Marisa Liliana Fernandez, Yasemin Özsürekçi, Wasin Matsee, Yenddy Carrero, Cristian Biscayart, Sergio Cimerman, Maria L Avila-Aguero, Roberto Debbag, Jose Brea, Alejandro Risquez, Jaime David Acosta-España, Rolando Ulloa-Gutierrez, Carlos Espinal, Carlos N Torres-Martinez, Marta González-Sanz, Aula Abbara, Jill Weatherhead, Mario Masana

Faculty, Staff and Students Publications

No abstract provided.

Pregnancy Outcomes After In Utero Exposure To Immune Checkpoint Inhibitors, Morgan Bou Zerdan, Bruna Kfoury, Eliane Aoun, Sarah Diane Hmaidan, Roni Nitecki Wilke, Jeffrey A How, Terri L Woodard, Pamela T Soliman, Laurie J Mckenzie

Faculty, Staff and Students Publications

Importance: Immune checkpoint inhibitors (ICIs) have transformed the management of cancers affecting reproductive-age patients, yet their impact on pregnancy outcomes remains incompletely understood. We describe two cases of maternal and fetal outcomes associated with ICI exposure during pregnancy and present a comprehensive literature review.

Methods: A retrospective chart review was conducted at MD Anderson Cancer Center (1 January 2015 to 31 December 2024) to identify patients exposed to ICIs during pregnancy. Clinical data including cancer type, treatment timing, pregnancy course, and maternal and neonatal outcomes were collected. A narrative literature review was also performed using PubMed to identify reported cases …

Development Of A Second-Generation Rarα Selective Antagonist As An Orally Bioavailable, Effective, Safe, And Reversible Male Contraceptive, Rui Shi, Kristen John, Xuan Qin, Ehfazul Haque, Taimeng Liang, Narsihmulu Cheryala, Feng Li, Henry L Wong, Gunda I Georg

Faculty, Staff and Students Publications

We report the design and SAR studies of benzopyran-, benzofuran-, and benzothiophene-derived inhibitors of the retinoic acid receptor alpha (RARα) for male contraception. SAR studies identified critical features influencing activity, such as the optimal positioning of antagonism moieties and substituents, leading to the discovery of (S)-4-(5-(2,8-dimethyl-5-(p-tolyl)-2H-chromen-3-yl)-1H-pyrrol-2-yl)­benzoic acid (compound 23). Compound 23 is a highly potent RARα inhibitor (IC50 = 0.051 nM) with excellent selectivity (>1650-fold over RARβ and >1960-fold over RARγ) and ADMET properties. Compound 23 is orally bioavailable and reduces sperm counts in mice for a full male contraceptive effect …

Mitochondria-Er Contact Sites (Mercs) In The Cell Cycle: Molecular Architecture And Functional Remodeling Across Cellular States, Eduardo Silva-Pavez, Bruno Torres-Gonzalez, Michelle Sotomayor, Benjamín Cartes-Saavedra, Dorian V. Ziegler, Yessia Hidalgo-Fadic, Ulises Ahumada-Castro

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria–endoplasmic reticulum (ER) contact sites (MERCS) are nanoscopic, dynamic platforms integrating metabolism, signaling, and stress responses to regulate cell fate. These nanoscopic interfaces remodel continuously to meet the demands of proliferating, quiescent, and senescent cells. We synthesize evidence that MERCS actively coordinate local Ca2+ signaling, non-vesicular lipid transfer, and proteostasis to shape mitochondrial function and cellular homeostasis. We discuss how MERCS architecture changes across the cell cycle and during arrest, distinguishing adaptive from maladaptive remodeling, and consider therapeutic potential in aging and age-related disease.

A Remote Intervention To Improve Medication Nonadherence Guided By A Marker Of Risk Derived From The Electronic Health Records Of Adolescent Transplant Recipients, Eyal Shemesh, Ravinder Anand, Rachel A Annunziato, Emily M Fredericks, Jennifer Garcia, Nitika Arora Gupta, Lawrence C Kleinman, Alyssa Kriegermeier, Krupa R Mysore, Vicky L Ng, Steven J Lobritto, Shreena Patel, Emily Rothbaum Perito, Elizabeth B Rand, Rene Romero, Robert S Venick, Sarah Duncan-Park, Jeffrey Mitchell, Sarah G Anderson, Margaret L Stuber, Miguel Reyes-Múgica, George V Mazariegos, Benjamin L Shneider

Faculty, Staff and Students Publications

Improving medication adherence in adolescents who had a liver transplant (iMALT), a prospective, block-randomized, single-blind, controlled multisite study in 13 pediatric transplant centers, used the medication level variability index (MLVI) to identify nonadherent adolescents. It compared a 2-year remote behavioral telemetric intervention (TI) that focused on adherence and addressed barriers to standard of care (SOC). The primary endpoint was the composite incidence of centrally determined (3 masked pathologists) rejection, death, retransplantation, or consent withdrawal. In 148 participants (TI group, n = 72 and the SOC group, n = 76), with a mean age 15.5 years, there were twice as many …

Early Life Exposure To Antibiotics Increases The Risk Of Myopia: A Retrospective Cohort Study, Peng-Tai Tien, Chang-Ching Wei, Sheng-Chun Lin, Ping Ping Meng, Yu-Te Huang, Jamie Jiin-Yi Chen, Ming-Yen Wu, Ying-Hsiu Shih, Tzu-Ju Hsu, Fuu-Jen Tsai, Yao-Chien Wang, Hui-Ju Lin, Lei Wan

BioMedicine

Background

Myopia is a growing health issue, expected to affect nearly half of the global population by 2050. Genetic predisposition and early environmental influences both play crucial roles in the development of myopia. Identifying modifiable risks and early interventions is critical. Antibiotics, commonly given to young children, may disrupt gut microbiota, which has been linked to ocular diseases in humans and animals.

Aim We aimed to investigate the association between antibiotic use in early life and the risk of developing myopia.

Methods Retrospective cohort study using data from a national health insurance database examined children aged three years or younger, …

Acidic Extracellular Ph-Induced Pth Secretion In Male Mouse Parathyroids Is Ogr1-Dependent, Yanmei Yang, Mengcun Chen, Mingshu Cui, Elisabeth Lashbrooks, Bin Wang

Center for Translational Medicine Faculty Papers

The role of extracellular acidity in regulating PTH secretion in cultured mouse parathyroid glands (PTGs) has not been studied to date, largely because of the technical difficulty of isolating mouse PTGs. We hypothesized that acidic extracellular pH directly stimulates PTH secretion through activation of a proton-sensing receptor, specifically ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68). To test this, we developed a method to reliably identify and isolate PTGs from male mice by administering 5-aminolevulinic acid, which induced selective fluorescence in these glands. Using this model, we demonstrate that acidic extracellular pH significantly stimulates PTH secretion in …

Cardiac Resynchronization Therapy: A Review, Caique M Ternes, Jitae A Kim, Anirban Basu, Kenneth A Ellenbogen, Mihail G Chelu

Faculty, Staff and Students Publications

Importance: Heart failure (HF) affects more than 64 million individuals worldwide, and acute HF is associated with 1-year mortality rates of 23.6% in North America and Europe. Cardiac dyssynchrony from conduction system disease may cause HF progression, particularly in patients with left ventricular (LV) systolic dysfunction.

Observations: Electrical dyssynchrony in HF most commonly presents as left bundle-branch block and affects 20% to 30% of patients with reduced LV ejection fraction (LVEF). Cardiac resynchronization therapy, which includes biventricular pacing and conduction system pacing, restores synchronous ventricular contraction and is recommended for patients with symptomatic HF despite optimal medical therapy, LVEF of …

Brain Age Prediction In Generalized Anxiety Disorder Using A Convolutional Neural Network, Corey Richier, André Zugman, Anita Harrewijn, Elise M Cardinale, Parmis Khosravi, Moji Aghajani, Willem B Bruin, Kevin Hilbert, Narcis Cardoner, Daniel Porta-Casteràs, Marta Cano, Savannah Gosnell, Ramiro Salas, Andrea P Jackowski, Pedro M Pan, Giovanni A Salum, Karina S Blair, James R Blair, Mohammed R Milad, Katie L Burkhouse, K Luan Phan, Heidi K Schroeder, Jeffrey R Strawn, Katja Beesdo-Baum, Neda Jahanshad, Sophia I Thomopoulos, Jared A Nielsen, Jordan W Smoller, Jair C Soares, Benson Mwangi, Mon-Ju Wu, Giovana B Zunta-Soares, Michal Assaf, Gretchen J Diefenbach, Paolo Brambilla, Eleonora Maggioni, David Hofmann, Thomas Straube, Carmen Andreescu, Rebecca B Price, Gisele G Manfro, Federica Agosta, Elisa Canu, Camilla Cividini, Massimo Filippi, Milutin Kostić, Ana Munjiza Jovanovic, Brenda Benson, Gabrielle F Freitag, Ellen Leibenluft, Grace V Ringlein, Kathryn Werwath, Hannah Zwiebel, Hans J Grabe, Sandra Van Der Auwera, Katharina Wittfeld, Henry Völzke, Robin Bülow, Nicholas L Balderston, Monique Ernst, Lilianne R Mujica-Parodi, Helena Van Nieuwenhuizen, Hugo D Critchley, Elena Makovac, Matteo Mancini, Frances Meeten, Cristina Ottaviani, Gregory A Fonzo, Martin P Paulus, Murray B Stein, Raquel E Gur, Ruben C Gur, Antonia N Kaczkurkin, Bart Larsen, Theodore D Satterthwaite, Jennifer Harper, Michael T Perino, Chad M Sylvester, Qiongru Yu, Patrick Mcclure, Francisco Pereira, Ulrike Lueken, Dick J Veltman, Paul M Thompson, Nynke A Groenewold, Janna Marie Bas-Hoogendam, Dan J Stein, Nic J A Van Der Wee, Anderson M Winkler, Daniel S Pine, Chelsea K Sawyers

Faculty, Staff and Student Publications

Higher predicted brain age difference has been associated with several psychiatric disorders. Generalized anxiety disorder (GAD) is associated with markers of accelerated aging. In this study, we determined brain predicted age difference (PAD) in individuals with GAD and healthy controls (HC) as well as group differences in PAD variability using voxel-wise structural MRI. The training dataset included 3511 controls, and the testing dataset included 1595 individuals with GAD and 4552 HC from the ENIGMA-Anxiety GAD Working Group. A convolutional neural network model using four input modalities per subject and a model ensemble approach was used to predict brain age. The …

Targeted Suppression Of Spp1 Inhibits Tumor Invasion And Metastasis In Nrf2 Hyperactivated Cisplatin Resistant Hnscc, Mutsuki Kawabe, Sujuan Yang, Lorena I Gomez-Bolanos, Shiro Takamatsu, Sylvia Flores, Patricia D Castro, Tsung-You Tsai, Arisa Nishikawa Kaga, Kento Okamoto, Mitchell J Frederick, Vlad C Sandulache, Humam Kadara, Jeffrey N Myers, Abdullah A Osman

Faculty, Staff and Students Publications

Background: Cisplatin remains the standard systemic therapy for the definitive treatment of head and neck squamous cell carcinoma (HNSCC), however, resistance to cisplatin continues to be a major barrier to effective treatment, particularly in tumors with NRF2 hyperactivation. Recent studies identify secreted phosphoprotein 1 (SPP1/osteopontin) as a key NRF2 target frequently overexpressed in cancers, where it drives aggressive tumor behavior, metastasis, chemoresistance, and, in some cases, immune suppression. Our recent data highlight SPP1 as one of the top 10 NRF2-upregulated genes in cisplatin-resistant HNSCC. However, its specific role in therapy resistance and metastasis in HNSCC remains unclear. Here, we investigate …

O-Glcnacylation As A Metabolic Integrator In Cardiovascular Physiology And Disease, Saima Shakil Malik, Xinchun Pi, Liang Xie

Faculty, Staff and Students Publications

No abstract provided.

Childcare Challenges Among Surgical Trainees And Faculty: A Single-Institution Study, Emma G Burke, Sarah Peiffer, Melissa Koci, Lindsay Dean, Kristy L Rialon, Michele Loor, Alice King

Faculty, Staff and Students Publications

Background: Previous studies have demonstrated the challenges of parenthood in surgical training and careers. However, certain aspects of childrearing for surgeons remain understudied. We aim to leftacterize the complexity and costs of childcare amongst surgical trainees and faculty.

Methods: An anonymous, self-administered survey was conducted within the Department of Surgery at a large academic medical center. Both male and female trainees and faculty were included in the analysis. Chi-square or Fisher's Exact test was performed.

Results: Forty-six respondents provided information about childcare costs, with 37% of respondents being residents or fellows. Trainees worked longer workhours (p = 0.003) than their …

Circulating Metabolites Associated With Protection Against Mycobacterium Tuberculosis Infection And Inhibition Of Mycobacterial Growth, Todia P Setiabudiawan, Lika Apriani, Julian Avila-Pacheco, Edwin Ardiansyah, Vinod Kumar, Bachti Alisjahbana, Ayesha J Verrall, Andrew R Dinardo, Agnes R Indrati, Vera P Mourits, L Charlotte J De Bree, Simone J C F M Moorlag, Clary B Clish, Leo A B Joosten, Arjan Van Laarhoven, Krista E Van Meijgaarden, Mihai G Netea, Simone A Joosten, Valerie A C M Koeken, Philip C Hill, Reinout Van Crevel

Faculty, Staff and Students Publications

A significant proportion of individuals who are heavily exposed to infectious tuberculosis patients do not acquire Mycobacterium tuberculosis (Mtb) infection, as detected by an interferon gamma release assay (IGRA). We examined circulating metabolite profiles and metabolic genotypes in 199 heavily exposed IGRA-negative tuberculosis household contacts in Indonesia. Based on differentially abundant metabolites, activity of several pathways including arachidonic acid, arginine and proline, glutathione, and tryptophan metabolism, correlated with a negative IGRA at three months. SNPs near PRODH (involved in arginine and proline metabolism) were associated with circulating proline concentrations and persistently negative IGRA results, while SNPstudys near AFMID (involved in …

The Perijunctional Zone Is A Molecularly Distinct Muscle Subdomain Altered In Duchenne Muscular Dystrophy, Seth G Haddix, Chuansheng Zhang, Yanhong Liu, Juan Oses-Prieto, Alma L Burlingame, Matthew N Rasband

Faculty, Staff and Students Publications

The neuromuscular junction (NMJ) is a well-established model for synapse development, structure, and function. Surrounding the NMJ is a narrow perijunctional zone (PJZ), enriched in muscle-specific voltage-gated sodium channels that prevent synaptic fatigue. Despite this role, the PJZ remains poorly characterized. To determine its molecular composition, we engineered mice to express the biotin ligase TurboID fused to the cell adhesion molecule neurofascin (Nfasc), and that localizes to the PJZ through ankyrin scaffolding proteins. Using proximity proteomics, we identify numerous PJZ-associated proteins, including Perilipin 4 (Plin4), that are highly enriched and clustered at the PJZ. We also perform proximity proteomics on …

Repurposing Semaglutide As An Adjunctive Treatment For Cocaine Use Disorder: Protocol For A Randomised Controlled Trial, Luba Yammine, Francesco Versace, Charles E Green, Heather E Webber, Jin Ho Yoon, Absalon D Gutierrez, Samuel J Leonard, Michael F Weaver, Joy Schmitz

Faculty, Staff and Student Publications

Introduction: Cocaine use disorder (CUD) is a significant public health concern in the USA, with considerable prevalence and mortality and no Food and Drug Administration (FDA)-approved pharmacotherapies. Recent advances in addiction science emphasise the need for novel, mechanism-based treatments. Glucagon-like peptide-1 receptor agonists, such as semaglutide, have shown promise in modulating reward-related behaviours and may offer therapeutic benefits for CUD. We present a study protocol evaluating semaglutide, as an adjunct to cognitive behavioural therapy (CBT), as a novel approach for treating CUD.

Methods and analysis: This is a randomised, double-blind, placebo-controlled trial enrolling 75 treatment-seeking adults with CUD. Participants will …

Brain-Wide Structural Markers Of Familial And Clinical Risk For Bipolar Disorder In Youth, Danella M Hafeman, Jamie Feldman, John Merranko, Mary L Phillips, Boris Birmaher, Si Gao, Yizhou Ma, Peter Kochunov

Faculty, Staff and Student Publications

Background: Bipolar Disorder (BD) is a severe mental illness, often emerging during adolescence, that is associated with significant psychosocial impairment. BD risk is elevated in offspring of affected parents, particularly those with antecedent symptoms (e.g., mood lability, subthreshold manic symptoms). However, robust, replicable brain-based markers of risk in this population are lacking. We assessed the degree to which the Regional Vulnerability Index for BD (RVI-BD), quantified as an individual's brain-wide similarity to BD patterns derived from meta-analytic studies, is elevated in youth at familial risk and correlates with symptom predictors of BD.

Methods: We recruited n=82 adolescents (10-15 years old), …

A Review Of Robotic Vnotes Surgery: Current Applications, Advantages, And Future Directions, Daniel Y Lovell, Qiannan Yang, Xiaoming Guan

Faculty, Staff and Students Publications

Over the past 500 years, the convergence of three distinct paths - vaginal surgery, laparoscopy, and robotic technologies - has enabled the development of robot-assisted vaginal natural orifice transluminal endoscopic surgery (RA-vNOTES). The ongoing evolution of vaginal surgery has led to contemporary procedures such as hysterectomy, myomectomy, sacrocolpopexy, adnexal interventions, and oncologic operations, applicable to a wide range of diagnoses and pathologies. This approach offers patients significant benefits, including superior cosmetic outcomes, less pain, lower infection rates, and faster recovery of baseline quality of life. Surgeons benefit from improved ergonomics, better visualization, the ability to use multiple instruments, and enhanced …

Phkg2 Confers Resistance Of Escc To Cisplatin And Enhances Cxcl8-Dependent Immunosuppression To Exacerbate Tumorigenesis, Jiayan Wu, Chengrui Zhong, Haosheng Zheng, Fei Qin, Xianyu Qin, Yuzhen Zheng, Junguo Chen, Gengfeng Wang, Bozhu Jian, Zui Liu, Xingping Yang, Chao Cheng, Guolin Li, Hongying Liao

Faculty, Staff and Students Publications

Cisplatin (DDP)-based chemotherapy serves as a foundational cornerstone in the clinical management of esophageal squamous cell carcinoma (ESCC). However, intrinsic or acquired resistance to DDP persists as a significant clinical challenge, severely undermining therapeutic efficacy and contributing to unfavorable patient prognoses. Through functional screening with a CRISPR/Cas9 knockout library, transcriptomic profiling of cisplatin-resistant cell lines and clinical specimens, and in vitro/in vivo validation assays, we identified PHKG2 as a key mediator of cisplatin resistance in ESCC. Mechanistically, PHKG2-mediated cisplatin resistance is driven by the phosphorylation of IGF2BP3 at residues T225 and T306. This post-translational modification enhances IGF2BP3 phase separation, thereby …

Movement-Stabilized Three-Dimensional Optical Recordings Of Membrane Potential Changes And Calcium Dynamics In Hippocampal Ca1 Dendrites, Kevin C Gonzalez, Satoshi Terada, Asako Noguchi, George N Zakka, Cliodhna O'Toole, Giuliana Bilbao, Luke Reynolds, Anna Jász, Borbála Kertész, Zoltán Szadai, Alissa Shen, François St-Pierre, Franck Polleux, Attila Losonczy, Balázs Rózsa

Faculty, Staff and Students Publications

Local dendritic computations are thought to critically influence neuronal signaling and plasticity yet remain largely unexplored in vivo due to challenges in stably imaging small structures at ultrafast timescales. We developed a 3D real-time motion correction platform for movement-stabilized, ultrafast two-photon voltage imaging. By co-labeling CA1 pyramidal neurons with voltage and calcium indicators, we simultaneously measured somato-dendritic and electro-calcium coupling at multiple dendritic sites. We characterized isolated dendritic spikes and distance-dependent backpropagation of naturally occurring and photostimulation-evoked bursts and single spikes. We found that bursts backpropagated more reliably than single spikes, validated that somato-dendritic coupling decreases with distance from soma, …

Latest In Resuscitation Research: Highlights From The 2025 American Heart Association's Resuscitation Science Symposium, Caleb T Suh, Clark G Owyang, Lindsay Shepard, Betty Yang, Ryan W Morgan, Daniel M Rolston, Catherine R Counts, Tommaso Scquizzato, James Horowitz, Tatyana Shvilkina, Katherine Berg, Sam Parnia, Sanam Alilou, Catherine Swarts, Ryan A Coute, Lama A Ammar, William C Herring, Thomas Lederer, Joaquin Araos, Benjamin S Abella, Cameron Dezfulian, Sarah M Perman, Felipe Teran

Faculty, Staff and Students Publications

No abstract provided.

Human Papillomavirus Vaccine Discourse And Sentiment On Reddit Before And After Covid-19: Mixed Methods Retrospective Cross-Sectional Study, Marcin Marciniak, Sean A Setzen, Deeya Bhattacharya, Jamie Masliah, Robin Powszok, Erich M Sturgis, Vanessa C Stubbs, Mihir K Bhayani

Faculty, Staff and Students Publications

Background: Human papillomavirus (HPV) is a sexually transmitted virus that causes various oropharyngeal and anogenital cancers. The HPV vaccine provides protection against several strains of HPV and is a key preventative tool against HPV-related cancers; however, vaccination rates remain suboptimal in the United States due to variable state mandates and misperceptions of vaccine efficacy and risks. As social media becomes an increasingly popular avenue for health discussions, platforms such as Reddit offer opportunities to understand public vaccine discourse, particularly among underrepresented groups. Furthermore, vaccine hesitancy and mistrust generally increased during the COVID-19 pandemic, potentially impacting HPV vaccination rates.

Objective: This …

Elongin B Orchestrates Chromatin And Transcriptional Programs In H3k27m-Mutant Diffuse Midline Glioma, Alan L Jiao, Rebecca L Murdaugh, Adam F Kebede, Claudia A Mimoso, Barry M Zee, Rosemary U Richard, Kwanha Yu, Caitlin L Bagnetto, Karen Adelman, Mariella G Filbin, Yang Shi, Jamie N Anastas

Faculty, Staff and Students Publications

Recurrent driver mutations in genes encoding histone H3 (H3.3K27M and H3.1K27M) are observed in ~80% of diffuse midline gliomas (DMG), which lead to aberrant gene regulation, yet the specific RNA polymerase II (Pol2) regulators that induce transcriptional dysregulation in DMG are not fully defined. We identified multiple regulators of Pol2 elongation as DMG genetic dependencies in a chromatin-focused CRISPR screen. Additional studies confirm that knockout (KO) of the Pol2 SIII complex gene elongin B (ELOB) inhibits DMG cell proliferation in tissue culture and tumor growth in xenograft models. Further genomic analyses reveal that ELOB binding sites are enriched in H3K27M …

Association Of Polygenic Risk Scores With Aortic Valve Calcium: The Multi-Ethnic Study Of Atherosclerosis, Seamus P Whelton, Jie Yao, Clary Clish, Alexis C Wood, Kent D Taylor, Michael J Blaha, Matthew Budoff, Natalie Marrero, George Thanassoulis, Wendy S Post, Xiuqing Guo, Jerome I Rotter

Faculty, Staff and Students Publications

Background: Aortic valve calcification (AVC) is the primary process leading to aortic stenosis. We examined whether polygenic risk scores (PRS) are associated with AVC beyond traditional atherosclerotic cardiovascular disease risk factors.

Methods: We included 6812 participants in MESA (Multi-Ethnic Study of Atherosclerosis) with computed tomography-measured AVC at Visit 1. Using previously published PRS we calculated weighted PRS, standardized within each ancestry group. The cross-sectional association per 1 SD higher PRS with AVC >0 was examined using multivariable logistic regression modeling with Bonferroni correction. The mean age was 62 years old, 53% were female, and 913 (13.4%) had AVC >0 at …

Deep-Learning Endomicroscope With Large Field-Of-View And Depth-Of-Field For Real-Time In Vivo Imaging Of Epithelial Cancer Hallmarks, Huayu Hou, Jimin Wu, Jinyun Liu, Vivek Boominathan, Argaja Shende, Karthik Goli, Jennifer Carns, Richard A Schwarz, Ann M Gillenwater, Preetha Ramalingam, Mila P Salcedo, Kathleen M Schmeler, Tomasz S Tkaczyk, Jacob T Robinson, Ashok Veeraraghavan, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep learning-enabled endomicroscope that breaks these constraints and achieves 20 mm2 FOV and 500 µm DOF with 4 µm resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep learning-optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface …

Early Neurodevelopmental Outcomes In A Child With Tuberous Sclerosis Complex Treated With Everolimus And Vigabatrin, Sarah Ml Wilson, Megan Samuels, Luana Pimentel, Shelley Varnado, Claire Sartwell, Rosleen Mansour, Deborah Pearson, Hope Northrup, Mary Kay Koenig

Faculty, Staff and Student Publications

Objectives: To report early neurodevelopmental outcomes in a child with Tuberous Sclerosis Complex (TSC) treated with everolimus and vigabatrin.

Methods: The authors report a five-year-old girl with Tuberous Sclerosis Complex who was initiated on vigabatrin at seven weeks old to treat infantile spasms and on everolimus at two months of age to treat a subependymal giant cell astrocytoma. Neuropsychological assessments were conducted in this patient at 12, 24, and 36 months using the Bayley-III and Vineland-II.

Results: On the Bayley-III, the patient had a high average cognitive composite score at 12 months and a high average language composite score at …