Digital Commons Network^™

Egfr Inhibitor-Resistant Lung Cancers Exhibit Collateral Sensitivity To A Covalent, Cysteine-Independent Keap1 Oligomerizing Molecular Bridge, Christopher F Bassil, Kerry Dillon, Gray R Anderson, Benjamin Mayro, Kayleigh N Askin, Peter S Winter, Stefan Harry, Samuel Gruber, Tierney M Hall, Jacob P Hoj, Christian Cerda-Smith, Haley M Hutchinson, Shane T Killarney, Ava Heffernan, Caroline Teddy, Katherine R Singleton, Li Qin, Kévin Jubien-Girard, Cécile Favreau, Guillaume Robert, Barr Tivon, Ella Livnah, Nir London, Rachid Benhida, Patrick Auberger, Ann Marie Pendergast, Liron Bar-Peled, David M Lonard, Anthony R Martin, Alexandre Puissant, Kris C Wood

Faculty, Staff and Students Publications

Targeted therapies have revolutionized cancer care. Unfortunately, most patients develop refractory, multifocal resistance to these therapies within a matter of months. Here, we demonstrate that the evolution of resistance to EGFR inhibitors in EGFR-mutant non-small cell lung cancer endows cells with hypersensitivity to a PAINS-like small molecule, MCB-613. Systematic proteomic, functional genomic, and biochemical studies revealed that MCB-613 binds KEAP1 in a covalent, cysteine-independent fashion, acting as a divalent molecular bridge that relies upon lysine residues in the KEAP1 dimerization domain to join monomers of KEAP1 together. Oligomerization of KEAP1 by MCB-613 sets into motion a fatal cascade of KEAP1 …

Ophiobolin A Impacts Mitochondrial Redox Biology In An Epithelial-Mesenchymal Transition (Emt)-Specific Manner, Haleigh N Parker, Yongfeng Tao, Jenna Tobin, Kayla L Haberman, Samantha Davis, Emily York, Alysia Martinez, Nobuyuki Matsumoto, Jaquelin Aroujo, Jun Hyoung Park, Bernd Zechmann, Benny Abraham Kaipparettu, Angela Boari, Christie M Sayes, Antonio Evidente, Alexander Kornienko, Benjamin Cravatt, Daniel Romo, Joseph H Taube

Faculty, Staff and Students Publications

Breast cancer progression is facilitated by the epithelial to mesenchymal transition (EMT), generating cancer cells with enhanced metastatic capacity and resistance to chemotherapeutics. The fungus-derived sesterterpenoid natural produce compound, ophiobolin A (OpA), possesses nanomolar cytotoxic activity and a high therapeutic index, although its molecular targets and mechanism of action are not well characterized. Herein, we utilized a model of mammary epithelial cells and breast cancer cell lines with and without EMT features to characterize the mechanism of selectivity towards EMT(+) cells by OpA. Proteins interacting with OpA in EMT(+) cells, including mitochondrial glutathione transporter SLC25A40, were identified through via mass …

Progress And Challenges In Profiling Protein-Rna And Protein-Associated Rna-Rna Interactions, Zhuoyi Song, Eric L Van Nostrand

Faculty, Staff and Students Publications

RNA binding proteins (RBPs) play essential roles in post-transcriptional gene regulation by interacting with a wide range of RNA targets. In addition to regulating RNA processing via individual RBP-RNA interactions, there is a growing appreciation of the regulatory impact of protein-associated RNA-RNA interactions that include both well-studied examples of small regulatory RNAs (e.g. microRNAs, snRNAs, snoRNAs, piRNAs) guiding ribonucleoprotein complexes to their targets as well as structured RNA elements defining the interaction landscape for an RBP. To elucidate the full scope of RBP-RNA interactions, CLIP ( crosslinking and immunoprecipitation)-based methods have emerged as powerful tools. Even with the wide application …

Resolution Of A Human Chromosomal Mystery: Evolutionary Complexity Revealed, Jeffrey Rogers

Faculty, Staff and Students Publications

The human complement of chromosomes differs from our closest primate relatives by virtue of a unique chromosome fusion event. In this issue of Cell Genomics, Yang et al. provide the first detailed analysis of the site of chromosome fusion and reconstruct the complex evolutionary relationships among the genomic elements within the human fusion site and their related sequences in our great ape relatives.

Prevalence And Outcomes Of Her2-Low Versus Her2-0 Status In Patients With Metastatic Breast Cancer, Akshara Singareeka Raghavendra, Diane D Liu, Senthil Damodaran, Sarah Pasyar, Yu Shen, Jason A Mouabbi, Carlos H Barcenas, Kelly K Hunt, Debu Tripathy

Faculty, Staff and Student Publications

Background: HER2-low breast cancer (HER2 immunohistochemical [IHC] score 1+, or IHC 2+ without HER2 gene amplification) is distinct from HER2-positive and HER2-0 breast cancer (IHC 0), with a differing prognosis and specific therapeutic options. The DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody-drug conjugate trastuzumab deruxtecan over standard chemotherapy in patients with metastatic breast cancer (MBC) defined as HER2-low. More recently, the DESTINY-Breast06 trial confirmed this benefit in hormone receptor-positive and HER2-ultralow (less than 1+, but with ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining) cases, prompting re-evaluation of HER2 diagnostic thresholds and treatment strategies.

Methods …

Autograft Enlargement After The Ross Procedure In Pediatric Patients: Somatic Growth Or Pathologic Dilatation?, Ioannis Zoupas, Alexander C Mills, Scott D Olson, Damien J Lapar

Faculty, Staff and Student Publications

Purpose of ReviewPulmonary autograft autotransplantation represents a popular surgical approach for pediatric patients requiring aortic valve replacement due to the potential for autograft enlargement to accommodate somatic growth. Nevertheless, autograft dilatation and the subsequent need for reintervention are quite common. Published data suggest that autograft enlargement may result from pathological passive remodeling rather than active somatic growth and vice versa. The present review serves to comprehensively evaluate available evidence related to the fate of the pulmonary autograft after the Ross procedure as it relates to the etiology, risk factors and patterns of autograft failure.ResultsStudies present conflicting results supporting both pathological …

Diet-Responsive Genetic Determinants Of Intestinal Colonization In The Yeast Candida Albicans, Musfirat Shubaita, Mazen Oneissi, Elena Lindemann-Pérez, Cecilia Fadhel Alvarez, Anne-Marie Krachler, Diana M Proctor, J Christian Pérez

Faculty, Staff and Student Publications

Dietary components influence microbial composition in the digestive tract. Although often viewed as energy sources, dietary components are likely to shape microbial determinants of intestinal colonization beyond metabolism. Here, we report that a dietary long-chain fatty acid enhances the yeast Candida albicans colonization of the murine gut partly by eliciting modifications to the fungal cell surface. Mice fed an oleic acid-rich diet were readily colonized by C. albicans and exhibited higher fungal load in feces compared with rodents fed an isocaloric control diet. Surprisingly, β-oxidation, a catabolic process to break down fatty acids for energy production, was dispensable for C. …

Efficacy And Safety Of Oral Pcsk9 Inhibitor Enlicitide In Adults With Heterozygous Familial Hypercholesterolemia: A Randomized Clinical Trial, Christie M Ballantyne, Laura Gellis, Jean-Claude Tardif, Puja Banka, Ann Marie Navar, Emil Andreas Asprusten, Russell Scott, Erik S G Stroes, Samar Froman, Geraldine Mendizabal, Fan Wang, Alberico L Catapano

Faculty, Staff and Students Publications

Importance: Persons with heterozygous familial hypercholesterolemia (HeFH) are at increased risk of atherosclerotic cardiovascular disease due to lifelong elevated levels of low-density lipoprotein cholesterol (LDL-C). Many patients with HeFH do not achieve guideline-recommended LDL-C goals with the currently available lipid-lowering therapies.

Objective: To evaluate the efficacy of enlicitide decanoate (an oral proprotein convertase subtilisin/kexin type 9 inhibitor) vs placebo in adults with HeFH requiring further lowering of LDL-C levels despite use of statin therapy.

Design, setting, and participants: This phase 3, randomized clinical trial included persons aged 18 years or older with HeFH currently using lipid-lowering therapy (taking at least …

Safety And Effectiveness Of Bolt-Mounted Versus Tunnelled External Ventricular Drains: A Systematic Review, Meta-Analysis And Trial-Sequential Analysis, Shaan Patel, Shiva A. Nischal, Ayush Sinha, Kush Kale, Pious D. Patel, Jack Jallo, Srinivas K. Prasad

Department of Neurosurgery Faculty Papers

BACKGROUND: External ventricular drains (EVDs) are fundamental to neurocritical care, yet substantial procedural heterogeneity persists, particularly regarding bolt-mounted versus tunnelled catheter fixation. The relative safety and effectiveness of these approaches remain unclear, with conflicting data from observational studies and a lack of trial-level evidence.

OBJECTIVE: To compare bolt-mounted and tunnelled EVDs across accuracy, reoperation, and key safety outcomes using systematic review, meta-analysis, and trial-sequential analysis.

METHODS: Following PRISMA guidelines, PubMed, Embase, and CENTRAL databases were searched (November 2025) for randomised or observational studies comparing bolt-mounted with tunnelled EVDs in adults. Two reviewers independently screened studies, extracted data, and assessed risk …

Tumor-Specific Immune Responses And Biomarkers In Pediatric Patients With High-Risk Hodgkin Lymphoma, Keri Toner, Lindsay A Renfro, Hema Dave, Gloria Pezzella, Qinglin Pei, Lisa Giulino-Roth, Terzah Horton, Frank G Keller, Kara M Kelly, Sharon M Castellino, Catherine M Bollard

Faculty, Staff and Students Publications

There is an unmet need to examine antitumor immune responses and predictive biomarkers in the peripheral blood to guide effective combination immunotherapies in classical Hodgkin lymphoma (cHL). We sought to evaluate T-cell specific immune responses as well as cytokine and chemokine profiles including levels of soluble CD30 (sCD30), sCD163, and thymus and activation-regulated chemokine (TARC) in relation to event-free survival in patients with cHL. The Children’s Oncology Group (COG) clinical trial AHOD1331 was a randomized phase 3 trial for patients with newly diagnosed high-risk cHL, aged 2 to 21 years, which compared standard chemotherapy and doxorubicin, bleomycin, vincristine, etoposide, prednisone, …

Repeated Mild Head Injury Establishes A Senescent Cranial Bone Marrow Niche That Impairs Brain Metabolism, Patrick J Devlin, Romeesa Khan, Trang H Do, Bryce E West, Janelle M Korf, Gary U Guzman, Chunfeng Tan, John Ahn, Rene Flores, Micheal E Maniskas, Sean P Marrelli, Anna Malovannaya, Erica Underwood, Rodney M Ritzel

Faculty, Staff and Students Publications

Traumatic brain injury (TBI) of any severity is associated with long-term systemic inflammation and increased risk of peripheral comorbidities, yet the mechanisms driving immune dysregulation and accelerated aging after repeated mild head impacts remain poorly defined. Here, we investigated the acute and chronic effects of repeated mild TBI (rmTBI) on distal and proximal bone marrow compartments in the femur and calvaria, respectively. Using a modified weight-drop mouse model delivering rotational and acceleration-deceleration forces (3 hits/week for up to 16 weeks), rmTBI produced no mortality, skull fracture, hemorrhage, or brain leukocyte infiltration. One day after three consecutive impacts, rmTBI induced robust …

The Biomedical Landscape Of Genomic Structural Variation In The Qatari Population, Elbay Aliyev, Najeeb Syed, Alessia Visconti, Taghi Aliyev, Aziz Belkadi, Mohammadmersad Ghorbani, Niccolò Rossi, Haroon Naeem, Geethanjali Devadoss Gandhi, Gaurav Thareja, Aljazi Al-Maraghi, Waleed Aamer, Amal Abdulsalam Ibrahim, Rulan Shaath, Farooq Omar Al-Ajli, Rozaimi Mohamad Razali, Fritz J Sedlazeck, Sonia Davila, Ammira Akil, Karsten Suhre, Younes Mokrab, Mario Falchi, Khalid A Fakhro

Faculty, Staff and Students Publications

We present a large-scale study of structural variation (SV) in the Qatari population, based on short-read whole-genome sequencing (WGS) of 6,141 individuals, identifying 153,946 variants across 5 classes reflecting the region's diversity and evolutionary history. Leveraging consanguinity and biobank phenotypes, we identify >180 putative gene knockouts, and use proteomics to show functional consequences in homozygotes. Conversely, 52 genes show significant depletion of homozygous deletions, eight of which cause severe pediatric disease or murine embryonic lethality. Examining phenotypic extremes uncovers several non-exonic homozygous deletions with large effect, including in SPIRE2 (creatinine), MAGI2 (leanness) and a chr19 microRNA cluster (extreme obesity). Further, …

Identifying Priority Research Questions For Decentralized Wastewater, Bryan W Brooks, Timothy Callahan, Jacob K Stanley, Jamie Holodak, Kevin M Stroski, Alissa H Cox, Thomas W Groves, Anish Jantrania, Jeff C Moeller, Kris Neset, Christopher Walker, Harry Zhang, Amal Bakchan, Kelly D Alley, Jim Bell, Allison Blodig, Eric Casey, Donna Cosper, Victor D'Amato, Mark A Elliott, Greg Graves, Roxanne Groover, Robert Himschoot, Mary G Lusk, Jillian Maxcy-Brown, David Meints, Rojelio Mejia, Matt Pace, Benjamin J Ryan, Brian Scheffe, Tom Schimelfenig, June E Wolfe, Sara F Heger

Faculty, Staff and Students Publications

Decentralized wastewater treatment and reuse represent critical infrastructure across the rural-periurban-urban continuum around the world. Effective, efficient, resilient, and equitable implementation of on-premise technologies and management systems is part of a One Water approach and necessary to protect public health and the environment, yet inconsistent delivery of essential public health services persists in many regions, including across states, tribes, and territories of the United States. We initiated a groundbreaking effort to understand challenges and to identify research opportunities related to the science and practice of decentralized wastewater. A horizon scanning exercise using a bottom up and transparent key questions approach …

Therapeutic Responses In Patients With Advanced Nsclc Enrolled In Early-Phase Clinical Trials At Md Anderson, Jeong Uk Lim, Heather Y Lin, Lei Kang, Hung Le, Tin-Yun Tang, Stephane Champiat, Ecaterina Elena Dumbrava, Xiuning Le, Aung Naing, Sarina A Piha-Paul, Jordi Rodon Ahnert, Apostolia Maria Tsimberidou, Timothy A Yap, Siqing Fu, Funda Meric-Bernstam, David S Hong

Faculty, Staff and Student Publications

We evaluated clinical outcomes and safety profiles in patients with non-small cell lung cancer (NSCLC) treated in early-phase trials. A retrospective review of 546 NSCLC cases treated from January 2016 to December 2024 at The University of Texas MD Anderson Cancer Center was performed using the MD Anderson CHIMERA database. Patients were categorized into seven groups based on treatment regimen. The overall objective response rate (ORR) was 19.9%, and the highest ORRs were in the targeted combination (30.8%) and targeted monotherapy (29.7%) groups. Gene alteration–matched therapy, serum albumin level, metastatic burden, treatment group, and liver metastasis were independently associated with …

Mini-Hyper-Cvd Plus Venetoclax And Navitoclax For Relapsed/Refractory Acute Lymphoblastic Leukemia, Nicholas J Short, Hagop Kantarjian, Nitin Jain, Tapan M Kadia, Jayastu Senapati, Fadi G Haddad, Manuel M Maroun, Koji Sasaki, Lianchun Xiao, Xuelin Huang, Omer Karrar, Regina Abramova, Min Zhao, Rebecca Garris, Marina Konopleva, Farhad Ravandi, Elias Jabbour

Faculty, Staff and Student Publications

No abstract provided.

Genome-Wide Gene By Sleepiness Interaction Analysis For Sleep Apnea, Pavithra Nagarajan, Nuzulul Kurniansyah, Jiwon Lee, Sina A Gharib, Yushan Xu, Yiyan Zhang, Brian Spitzer, Tariq Faquih, Hufeng Zhou, Eric Boerwinkle, Han Chen, Daniel J Gottlieb, Xiuqing Guo, Nancy L Heard-Costa, Bertha A Hidalgo, Daniel Levy, Peter Y Liu, Hao Mei, Rebecca Montalvan, Sutapa Mukherjee, Kari E North, George T O'Connor, Lyle J Palmer, Sanjay R Patel, Bruce M Psaty, Shaun M Purcell, Laura M Raffield, Stephen S Rich, Jerome I Rotter, Richa Saxena, Albert V Smith, Katie L Stone, Xiaofeng Zhu, Topmed Sleep Trait Working Group, Brian E Cade, Tamar Sofer, Susan Redline, Heming Wang

Faculty, Staff and Student Publications

Study objectives: Excessive daytime sleepiness (EDS), influenced by environmental and social-behavioral factors, is reported by a subset of patients with sleep apnea-a group that may be at elevated cardiovascular risk. However, it is unclear whether sleep apnea with and without EDS have distinct genetic underpinnings. In this study, we perform gene-by-EDS interaction analyses for apnea hypopnea index, a diagnostic marker of sleep apnea severity, to understand EDS's influence on its underlying genetic risk.

Methods: Discovery interaction analyses for common variants and gene-based rare variants were conducted respectively using multi-ethnic Trans-Omics for Precision Medicine (N = 11 619) data, followed by …

Perioperative Fluid Management In Pancreaticoduodenectomy In The Era Of Goal-Directed Fluid Therapy: A Review Of The Literature, Meghan D Grim, Richard Zheng, Nader Hanna, Harish Lavu, Charles J. Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

BACKGROUND: Pancreaticoduodenectomy (PD) is the only curative option for localized pancreatic head and periampullary malignancies. However, PD is associated with significant perioperative morbidity. Perioperative fluid management has emerged as an important modifiable factor influencing surgical outcomes in PD.

METHODS: In this qualitative review, PubMed/Medline searches were performed between March and August 2025 to review the terms "pancreaticoduodenectomy," "fluid management," "Enhanced Recovery After Surgery," "complications," and related terms.

RESULTS: Historically, liberal fluid administration was favored to compensate for third-space losses, but contemporary evidence has linked excessive fluid volumes to complications, such as postoperative pancreatic fistula, anastomotic edema, and increased inflammatory responses. …

Disease Burden Of Asthma Patients Utilizing Short-Acting Beta-2 Agonist-Only Inhalers As Rescue In The United States, Njira Lugogo, Rena C. Moon, Yen Chung, Joy David, Omar Motawakel, Ning A. Rosenthal, Neil Skolnik

Department of Family & Community Medicine Faculty Papers

Purpose: We aimed to describe the disease burden of asthma and examine relationships between short-acting beta-2 agonist (SABA) use and asthma exacerbations. Patients and Methods: This retrospective cohort study used geographically diverse Premier Healthcare Database (PHD) and linked insurance claims (10/01/2021-09/30/2022) for US patients aged ≥18 years with a SABA-only prescription and a history of asthma exacerbation within 12 months before index date (the earliest SABA prescription date). Three asthma control groups were defined based on SABA usage: well controlled-low (0–1 prescriptions), not well controlled-medium (2–3 prescriptions), very poorly controlled-high (≥4 prescriptions). Four asthma severity groups were defined using asthma …

Dynamic Fib-4 Score Changes And Hcc Risk In Patients With Masld And Elevated Liver Enzymes: A Nationwide Cohort Study, Yee Hui Yeo, Hsiu J Ho, Tsai-Wei Huang, Teng-Yu Lee, Ju Dong Yang, George Cholankeril, Chien-Jen Chen, Hawi-I Yang, Chuen-Fei Chen, Hung-Chuen Chang, Chun-Ying Wu

Faculty, Staff and Students Publications

Introduction: Hepatocellular carcinoma (HCC) can develop in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) without cirrhosis, especially in those with elevated liver enzymes. However, there is currently no low-cost, scalable screening tool for this population. To address this need, we investigated the association between serial changes in FIB-4 (fibrosis-4) scores over a 3-year period and the risk of developing HCC in a large, diverse cohort of patients with MASLD without cirrhosis.

Methods: This study utilized a nationwide cohort from the National Health Insurance Research Database (NHIRD), including 810,698 patients with MASLD who had demographic and laboratory data at baseline …

Chek2 Loss Endows Chemotherapy Resistance To Hematopoietic Stem Cells, Jing Zhou, Tianyuan Hu, Dian Li, Sanming Li, Minhua Li, Xiangguo Shi, Daisuke Nakada

Faculty, Staff and Students Publications

Individuals with history of chemo- or radiotherapy frequently exhibit somatic mosaicism in the blood, often involving mutations in genes responsible for DNA damage responses (DDR), such as CHEK2. However, the mechanisms by which CHEK2 mutations promote the expansion of mutant cells following chemo- or radiotherapy remain poorly understood. Here, we demonstrate that loss of CHEK2 confers resistance to chemotherapy in hematopoietic stem and progenitor cells (HSPCs). Through a CRISPR-based screen, we identified CHEK2 as a gene whose loss enhances resistance to cytotoxic chemotherapies. A complementary drug screen revealed that CHEK2-mutant cells are also resistant to DNA hypomethylating agents. Chek2-deficient HSPCs …

High-Dose Oral Pyrophosphate Inhibits Connective Tissue Calcification In Abcc6 Null Mice But May Affect Bone Structure, Ibtesam Rajpar, Nicholas Yancy, Jacob Beiriger, Christina Shao, Syed Naqvi, Deana Mancuso, Fatemeh Niaziorimi, Ryan E Tomlinson, Koen Van De Wetering

Department of Orthopaedic Surgery Faculty Papers

Pseudoxanthoma elasticum (PXE) is a rare inherited disorder marked by abnormal calcium phosphate deposition in soft connective tissues, particularly the skin, arteries, and eyes. It is caused by inactivating mutations in the ABCC6 gene, which encodes a hepatic efflux transporter. Loss of ABCC6 function leads to reduced plasma levels of pyrophosphate (PPi), a key inhibitor of calcification, thereby promoting ectopic mineralization. Oral PPi therapy has emerged as a potential treatment, but its effectiveness is uncertain. Most ingested PPi is hydrolyzed in the gut to inorganic phosphate, which may worsen calcification. Moreover, its impact on mineralized tissues remains largely unexplored. Abcc6−/− …

Germline Hla Heterozygosity Is Associated With Decreased Lung Cancer Risk, Taotao Tan, Vikram R Shaw, Jinyoung Byun, Hyun-Sung Lee, Younghun Han, Yafang Li, Rayjean J Hung, David C Christiani, Xin-An Wang, Mattias Johansson, Xiangjun Xiao, David Zaridze, Stig Egil Bojesen, Sanjay Shete, Demetrios Albanes, Melinda C Aldrich, Adonina Tardon, Guillermo Fernandez-Tardon, Loïc Le Marchand, Gad Rennert, Heike Bickeböller, H-Erich Wichmann, Angela Risch, John K Field, Michael Davies, Penella Woll, Lambertus A Kiemeney, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Mikael Johansson, Kjell Grankvist, Matthew B Schabath, Angeline Andrew, Philip Lazarus, Susanne M Arnold, Dakai Zhu, Maria Teresa Landi, James Mckay, Christopher Amos, Chao Cheng

Faculty, Staff and Students Publications

Heterozygosity at human leukocyte antigen (HLA) loci may improve lung cancer immunosurveillance by increasing recognition of the tumor by the immune system. Previous studies utilizing data from population-level biobanks, such as the United Kingdom Biobank and FinnGen, have identified an association between germline HLA class-II heterozygosity and reduced lung cancer risk in smokers. In the present study, we evaluate the association between HLA heterozygosity and lung cancer in a large case-control study (15,302 cases; 14,580 controls) with imputed HLA allele-type information, comparing differences in HLA heterozygosity between smokers and non-smokers, amongst lung cancer subtypes, and at 2- and 4-digit HLA …

Tet2-Mutant Clonal Hematopoiesis Enhances Macrophage Antigen Presentation And Improves Immune Checkpoint Therapy In Solid Tumors, Shelley Herbrich, Mehdi Chaib, Swetha Anandhan, Samuel W Andrewes, Ashwat Nagarajan, Baoxiang Guan, Nishant Gandhi, Jared Gilliam, Milan Radovich, Padmanee Sharma

Faculty, Staff and Student Publications

Clonal hematopoiesis (CH) is detectable in upwards of 20% of patients with solid tumors and is associated with worsened prognosis; however, its role in tumor immunology and immune checkpoint therapy (ICT) is unknown. Using a bone marrow chimera model of Tet2+/mut CH in mice with solid tumors, we found the Tet2-mutant myeloid cells are abundant in the tumor microenvironment and contributed to an improved response to ICT. Mechanistically, Tet2+/mut macrophages inside the tumor act as immunogenic antigen-presenting cells that more effectively cross-prime naive CD8+ T cells in response to IFNγ. In human cohorts of 35,971 non-small cell lung cancer patients …

Adipose Stromal Cell-Derived Cancer-Associated Fibroblasts Promote Pancreatic Adenocarcinoma Progression Through Sfrp4 Signaling, Joseph Rupert, Lingyi Cai, Alexes C Daquinag, Dimitris Anastassiou, Mikhail G Kolonin

Faculty, Staff and Student Publications

Background/objectives: Progression of pancreatic ductal adenocarcinoma (PDAC) and other carcinomas relies on cancer-associated fibroblasts (CAFs). A subset of CAFs is derived from adipose stromal cells (ASCs) recruited by tumors and the ASC-CAF conversion has been associated with invasiveness and poor prognosis.

Methods: To explore the underlying molecular mechanisms, we used a model based on primary ASCs derived from human visceral adipose tissue co-cultured with human PDAC cell line Capan-1. To investigate cancer progression in vivo, we also used mice orthotopically grafted with mouse KPC cells.

Results: Genomic analysis revealed that Capan-1 co-culture induces Wnt and TGFβ signaling and extracellular matrix …

Spatial Omics At The Forefront: Emerging Technologies, Analytical Innovations, And Clinical Applications, Yunhe Liu, Yibo Dai, Linghua Wang

Faculty, Staff and Student Publications

Spatial omics transforms our understanding of cancer by revealing how tumor cells and the microenvironment are organized, interact, and evolve within tissues. Here, we synthesize advances in spatial technologies that map tumor ecosystems with unprecedented fidelity. We highlighted analytical breakthroughs-including multimodal integration and emerging spatial foundation models-that resolve functional niches and spatial communities, converting spatial patterns into mechanistic insights. We summarize how spatially organized features, from immune hubs to microbiota and neural interfaces, shape tumor evolution and clinical outcomes. We then outline how spatial approaches illuminate precancer biology, metastatic adaptation, and therapy response. Bridging discovery and translation, we provide a …

Tumor-Infiltrating Bacteria Disrupt Cancer Epithelial Cell Interactions And Induce Cell-Cycle Arrest, Jorge Luis Galeano Niño, Falk Ponath, Victor A Ajisafe, Clara R Becker, Andrew G Kempchinsky, Martha A Zepeda-Rivera, Javier A Gomez, Hanrui Wu, Jessica G Terrazas, Heather Bouzek, Elizabeth Cromwell, Pritha Chanana, Matthew Wong, Ashish Damania, Michael G White, Y Nancy You, Scott Kopetz, Nadim J Ajami, Jennifer A Wargo, Christopher D Johnston, Susan Bullman

Faculty, Staff and Student Publications

Tumor-infiltrating bacteria are increasingly recognized as modulators of cancer progression and therapy resistance. We describe a mechanism by which extracellular intratumoral bacteria, including Fusobacterium, modulate cancer epithelial cell behavior. Spatial imaging and single-cell spatial transcriptomics show that these bacteria predominantly localize extracellularly within tumor microniches of colorectal and oral cancers, characterized by reduced cell density, transcriptional activity, and proliferation. In vitro, Fusobacterium nucleatum disrupts epithelial contacts, inducing G0-G1 arrest and transcriptional quiescence. This state confers 5-fluorouracil resistance and remodels the tumor microenvironment. Findings were validated by live-cell imaging, spatial profiling, mouse models, and a 52-patient colorectal cancer cohort. Transcriptomics reveals …

Blood Product Transfusion And Coagulopathy In Children With Traumatic Brain Injury: A Narrative Review., Robert Marcel T. Huibonhoa, Niranjan Vijayakumar, Daniel Kelly, Oliver Karam, Madhuradhar Chegondi

Manuscripts, Articles, Book Chapters and Other Papers

Traumatic brain injury (TBI) is a leading cause of critical illness and mortality in children. Transfusion of blood products, a common intervention in the management of pediatric TBI, has important implications for related principles, including trauma-induced coagulopathy, cerebral perfusion, and cerebral oxygen delivery. Knowledge gaps persist due to the limited availability of pediatric-specific data regarding blood product transfusion in TBI. In particular, there is a lack of prospective studies defining appropriate specific laboratory thresholds and transfusion targets, as well as insufficient evidence to guide the weighing of potential benefits against transfusion-related risks in this population. Although blood product transfusion in …

Grover's Disease: A Review Of The Current Treatment Options, Dustin Ross, Dmsc, Mph, Pa-C

Lynchburg Journal of Medical Science

Grover’s disease, also known as transient acantholytic dermatosis, is an uncommon dermatologic condition characterized by pruritic papulovesicular eruptions that predominantly affect the trunk of older adults. Although the disease is often self-limited, it may significantly impair quality of life. This review summarizes treatment options and emerging therapies for Grover’s disease reported in the literature since 2019. A comprehensive search of PubMed and MEDLINE identified 1,068 records, of which thirteen publications met inclusion criteria, including one systematic review, one narrative review, one nonrandomized controlled study, nine case reports, and one fact sheet, representing a total of 337 patients. The literature demonstrates …

Proton Versus Photon Radiotherapy For Patients With Oropharyngeal Cancer In The Usa: A Multicentre, Randomised, Open-Label, Non-Inferiority Phase 3 Trial, Steven J Frank, Paul M Busse, J Jack Lee, David I Rosenthal, Mike Hernandez, David M Swanson, Adam S Garden, G Brandon Gunn, Samir H Patel, James W Snider, Daniel J Ma, Jason K Molitoris, Nancy Y Lee, Upendra Parvathaneni, Mark W Mcdonald, Noah S Kalman, Alexander Lin, Nasiruddin Mohammed, Christina Henson, Christian Hyde, Gopal K Bajaj, Sanford R Katz, Roi Dagan, William H Morrison, Jay P Reddy, C David Fuller, Shalin J Shah, Jack Phan, Gregory M Chronowski, Lauren Mayo, Erich M Sturgis, Renata Ferrarotto, Xiaorong R Zhu, Xiaodong Zhang, Li Wang, Katherine A Hutcheson, Adel K El-Naggar, Amy C Moreno, Anna Lee, Michael T Spiotto, Neil D Gross, Stephen Y Lai, Jay J Liao, Jonathan Paly, Zhongxing Liao, Robert L Foote

Faculty, Staff and Student Publications

Background: Radiotherapy is an integral component of treatment for oropharyngeal cancer. Toxicity from the current state-of-the-art photon radiotherapy, intensity-modulated radiation therapy (IMRT), has prompted the search for alternative, less toxic therapies. One such alternative that might de-intensify treatment is proton therapy. In this trial, we aimed to directly compare IMRT with intensity-modulated proton therapy (IMPT), both concurrent with systemic therapy, hypothesising comparable disease control and survival and lower toxicity.

Methods: This randomised, multicentre, open-label, non-inferiority, phase 3 trial was conducted in 21 sites (cancer centres or universities) in the USA. Patients (aged ≥18 years) with stage III or stage IV …

Il-18 Metabolically Reprograms Car-Expressing Natural Killer T Cells And Enhances Their Antitumor Activity, Gabriel A Barragán Bravo, David A De La Cerda, Elisa Landoni, Kshiti Dholakia, Piotr Humeniuk, Leidy D Caraballo Galva, Ying Wang, Gengwen Tian, Boning Yang, Linjie Guo, Michael S Wood, Xavier Rios, Xin Xu, Amy N Courtney, Erica J Di Pierro, Joan Jacob, Yi-Han Li, Akshaya Adaikkalavan, Norihiro Watanabe, Sufeng Mao, George Miles, Gianpietro Dotti, Leonid S Metelitsa

Faculty, Staff and Students Publications

Invariant natural killer T cells (NKTs) have intrinsic anti-tumor properties that make them promising candidates for chimeric antigen receptor (CAR) immunotherapies. Transgenic cytokine expression can enhance cellular therapy potency, and we hypothesized that co-expressing IL-18 alone or with IL-15 would boost CAR-NKT therapeutic potential. To test this, we generated retroviral constructs expressing IL-15 and/or IL-18 with an inducible caspase 9 safety switch and co-transduced them with a GD2-specific CAR into human NKTs. Co-expression of IL-18 or IL-15/IL-18 increased CAR-NKT cytotoxicity, proliferation, and cytokine secretion in vitro compared to IL-15 alone. IL-18 also enhanced GPC3.CAR and CD19.CAR NKT activity against hepatocellular …