Digital Commons Network^™

A Programmable Genetic Platform For Engineering Noninvasive Biosensors, Asish N Chacko, Kaamini M Dhanabalan, Jinyang Wan, Roy Chien, Nolan T Anderson, Binzhi Xu, Katie Pham, Ritu Tiwari, Arnab Mukherjee

Faculty, Staff and Student Publications

Creating genetic sensors for noninvasive visualization of biological activities in optically opaque tissues holds immense potential for basic research and the development of genetic and cell-based therapies. Magnetic resonance imaging (MRI) stands out among deep tissue imaging methods for its ability to generate high-resolution images without ionizing radiation. However, the adoption of MRI as a mainstream biomolecular technology has been hindered by the lack of adaptable methods to link molecular events with genetically encodable contrast. Here, we introduce modular aquaporin-based protease-activatable probes for enhanced reporting (MAPPER), a platform for the systematic creation of genetic sensors for MRI. To develop MAPPER, …

Advances In Targeting Her2 Across Cancer Subtypes: A Pan-Tumor Approach, Taiwo Adesoye, Ecaterina E Dumbrava, Kanwal P S Raghav, Aysegul A Sahin, Hui Chen, Sunyoung S Lee, Milind M Javle, Shubham Pant, Omar Alhalabi, Xiuning Le, Vicente Valero, Paula R Pohlmann, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Human epidermal growth factor receptor 2 (HER2) is an established therapeutic target in multiple solid tumors, particularly breast and gastric cancers. Significant advancements have been made in the development of HER2-targeted therapies, including monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates (ADC), and novel bispecific antibodies. These agents have revolutionized the treatment landscape for HER2-positive metastatic cancers, resulting in improved progression-free and overall survival, and quality of life for patients. Beyond breast and gastric cancers, HER2 expression/amplification has been observed in other solid tumors, such as colorectal, lung, bladder, ovarian, and biliary tract cancers, offering new opportunities for personalized therapy in …

Rab5c Increases Endothelial Release Of Vwf By Regulating Vesicle Trafficking, Paula Reventun, Pablo Toledano-Sanz, Maria Delgado-Marin, Maria Viskadourou, D Brian Foster, Paul S De Vries, Maria Sabater-Lleal, Nunzio Alcharani, Claudia Gonzalez-Cucharero, William O Osburn, Alanna C Morrison, Alisa S Wolberg, Nicholas L Smith, Marios Arvanitis, Charles J Lowenstein

Faculty, Staff and Student Publications

Background: Abnormal levels of VWF (von Willebrand Factor) are a risk factor for venous thromboembolism (VTE) and bleeding. Genome-wide association studies for VWF have identified novel candidate genes that may regulate VWF levels in humans, including RAB5C (RAS-associated protein RAB5C). We hypothesized that RAB5C regulates VWF release from endothelial cells.

Methods: We studied the effect of RAB5C on vesicle trafficking in human endothelial cells. We performed CRISPR (clustered regularly interspaced short palindromic repeats) interference targeting 2 genetic variants linked to altered VWF levels and evaluated RAB5C expression by reverse transcription-quantitative polymerase chain reaction. We silenced RAB5C or overexpressed RAB5C wild-type, …

Dna Methyltransferase Inhibitors In Hematological Malignancies And Solid Tumors, Valentin Wenger, Guillermo Garcia-Manero, Robert Zeiser, Michael Lübbert

Faculty, Staff and Student Publications

Epigenetic modifications such as DNA methylation play a fundamental role in oncogenesis and the progression of neoplasms neoplasias. DNA methyltransferase inhibitors (DNMTi) constitute a family of therapeutic agents that impede the methylation at the 5-position on cytosine nucleotides, thereby modulating the epigenetic regulation of tumor suppressor genes, oncogenes, and other key regulatory genes. The first-generation DNMTi azacitidine and decitabine have demonstrated substantial efficacy in the treatment of medically non-fit, older patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy (IC), by virtue of their favorable safety profile. Despite these clinical achievements, however, single-agent DNMTi treatment …

Bridging Hypoxia And Vision Loss: The Emerging Role Of Connexins In Local And Systemic Eye Diseases, Xianping Zhang, Yalong Cheng, Jean X Jiang, Yuting Li

Faculty, Staff and Student Publications

Hypoxic eye diseases represent a pivotal yet often underappreciated contributor to the onset and progression of many retinal disorders. When hypoxia persists or exceeds the tissue's compensatory capacity, it triggers pathological retinal neovascularization, blood-retinal barrier disruption, and neuronal apoptosis, ultimately resulting in irreversible visual impairment. Connexins (Cxs) form gap junction channels and hemichannels and regulate retinal cell proliferation, differentiation, and survival, thereby playing a central regulatory role in the pathogenesis of hypoxic ocular diseases. In addition to gap junctions, Cx hemichannels promote transmission of molecules between intra- and extracellular environments, further influencing retinal homeostasis under hypoxic stress. This review synthesizes …

Epilepsy Disease Classification: A Community Effort To Enhance The Mondo Disease Ontology, Nicole Vasilevsky, Sarah Gehrke, Kathleen Mullen, Subit Barua, Ian Braun, Tobias Brünger, Curtis Coughlin, Alina Ivaniuk, Daniel Korn, Dennis Lal, Stephanie Marsh, Elaine O'Loughlin, Daniel Olson, Yousif Shwetar, Christalena Sofocleous, Vanessa Vogel-Farley, Heidi Grabenstatter, Melissa Haendel, Christopher Mungall, Sabrina Toro

Faculty, Staff and Student Publications

Motivation: Epilepsy is a diverse group of neurological disorders affecting over 50 million people worldwide. While common epilepsy types are well studied, rare epilepsies-often severe and genetically complex-pose significant challenges in diagnosis, research, and treatment. Accurate and interoperable etiology and disease classifications are critical for improving data sharing, supporting clinical decision-making, and advancing rare disease research.

Results: To enhance the accuracy of epilepsy-related disease concept representation within the Mondo Disease Ontology (Mondo), we conducted a series of expert-driven workshops in collaboration with the team from the Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP). Specialists in epileptology, genetics, neurodevelopment, biomedical …

Whole Genome Sequence Analysis Of Pulmonary Function And Copd In 44,287 Multi-Ancestry Participants, Wonji Kim, Lucinda Antonacci-Fulton, Susan K Dutcher, Et Al.

2020-Current year OA Pubs

BACKGROUND: Whole genome sequence (WGS) data in multi-ancestry samples supports discovery of low-frequency or population-specific genetic variants associated with chronic obstructive pulmonary disease (COPD) and lung function.

RESULTS: We performed single variant, structural variant, and gene-based analysis of pulmonary function (FEV

CONCLUSIONS: Large-scale multi-ancestry WGS analysis improves variant discovery and fine-mapping resolution for lung function and COPD and highlights biologically relevant genes and pathways.

The Effects Of Bone-Remodeling Therapy On Survival, Pain, And Skeletal Related Events In The Setting Of Renal Cell Carcinoma With Bone Metastases: A Multicenter Investigation From A Large Global Health Research Network (Trinetx), Brian H. Im, Kevin K. Zarrabi, Aaron R. Hochberg, Mihir M. Shah, Md, James R. Mark, Joseph K. Izes, Patrick T. Gomella, Costas D. Lallas, Leonard G. Gomella, Adam R. Metwalli

Department of Urology Faculty Papers

INTRODUCTION: Renal cell carcinoma (RCC) is the most common renal malignancy-bone metastases (BM) are indicative of aggressive disease with a poor prognosis. We aim to evaluate the overall mortality of patients with RCC with and without BM, and to elucidate the effects of bone-remodeling therapy on mortality, incidence of skeletal-related events, and opioid usage patterns in patients with BM.

METHODS: A retrospective cohort study was conducted using TriNetX, a large, collaborative network sourced from electronic medical records of over 110 million patients from over 100 healthcare organizations. All adult patients with RCC and RCC with BM were queried.

RESULTS: There …

The Impact Of Skin Tone On Performance Of Pulse Oximeters Used By Nhs England Covid Oximetry @Home Scheme: Measurement And Diagnostic Accuracy Study, Exakt Study Investigators, Daniel S Martin, James C Doidge, Doug Gould, Tasnin Shahid, Alex Cowden, Walton N Charles, Amelia Francis Johnson, Roger Garrett, Catherine Mbema, Olusegun Olusanya, Eugene Healy, Kathryn Rowan, Paul Mouncey, David A Harrison

Peninsula Medical School

OBJECTIVES: To assess the impact of skin tone on the measurement and diagnostic accuracy of five fingertip pulse oximeters used by patients in the NHS (National Health Service) England COVID Oximetry @home scheme.

DESIGN: Measurement and diagnostic accuracy study (exploring pulse oximeter accuracy across skin tones-EXAKT).

SETTING: Twenty four intensive care units in England between June 2022 and August 2024.

PARTICIPANTS: 903 critically ill adults admitted to intensive care units screened for or enrolled into a trial evaluating different approaches to oxygen therapy.

INTERVENTIONS: Pulse oximetry derived peripheral oxygen saturation (SpO2) measurements were compared with paired arterial oxygen saturation (SaO2) …

Primate Gut Microbiota Induce Evolutionarily Salient Changes In Mouse Neurodevelopment., Alex R Decasien, Jacob E Aronoff, Elizabeth K Mallott, Sahana Kuthyar, Sriram Chitta, Brian T Layden, Maria L Savo Sardaro, Stanton Gray, Lawrence E Williams, Emma R Liechty, Hyo M Lee, Won Lee, James P Curley, Christopher W Kuzawa, Katherine R Amato

Faculty Research 2026

Multiple primate species, including humans, evolved brains that are exceptionally large relative to their body sizes. These large brains coevolved with metabolic adaptations that enhance cerebral energy supply, including increased circulating glucose levels. While the gut microbiota (GM) is known to influence host metabolism, its potential role in primate brain evolution remains unclear. To investigate this, we inoculated germ-free mice with the GMs of primate species selected to separate the effects of brain size (encephalization) from phylogenetic relatedness: humans (large-brained, Catarrhini), macaques (smaller-brained, Catarrhini), and squirrel monkeys (large-brained, Platyrrhini). We first show that differences in brain gene expression between mice …

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 …

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 …

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. …

A Chemogenetic Approach For Temporal And Cell-Specific Activation Of Endogenous Gpcrs In Vivo, Gwendolyn Shingles, Qianqian Pang, Jian Weng, Ryan Singer, Waleed Babar, Jiaqi Shen, Luis Vazquez-Rivera, Yao Chen, Peng Li, Wenjing Wang

2020-Current year OA Pubs

Cell-specific regulation of endogenous G protein-coupled receptors (GPCRs) is crucial for understanding their roles in physiological processes. We present chemogenetic tools using shield-1-dependent irreversible protein switches to regulate peptide agonist activity. To demonstrate this platform, we engineered chemogenetically regulated pituitary adenylate cyclase activating polypeptide (cPACAP), which exhibited >15-fold chemical-dependent regulation of endogenous receptor activity. In vivo application of cPACAP allowed neuronal activation via the endogenous receptor for PACAP, engaging neural circuits that control respiratory and feeding behaviors. By integrating cPACAP with transgenic mice, we selectively activated endogenous PACAP receptor signaling in hypocretin-expressing neurons of the lateral hypothalamic area (LHA), revealing …

Self-Efficacy Change Among Diverse Family Caregivers In Dementia Care, Deborah M Oyeyemi, Erich J Greene, Yunshan Xu, David R Lee, Rafael Samper-Ternent, Maya L Lichtenstein, Alan Stevens, Jeff D Williamson, Arun S Karlamangla, Debra Saliba, David B Reuben

Faculty, Staff and Student Publications

Objectives: To determine whether changes in caregiver self-efficacy (beliefs about one's ability to manage dementia-related problems and access help) differed by caregiver race and ethnicity across all participants enrolled in a large pragmatic trial of comprehensive dementia care.

Methods: In the Dementia Care Study (D-CARE), community-dwelling older adults with dementia and their unpaid family caregivers were randomized to receive usual care, community-based, or health system-based comprehensive dementia care. Caregiver self-efficacy was assessed at baseline, 6 months, and 18 months using a 4-item scale (range 4-20, higher scores indicate greater self-efficacy). Among all caregivers, we compared least squares means for overall …

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 …

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 …

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 …

The Computationally Designed Tri2-2 Miniprotein Inhibitor Protects Against Multiple Sars-Cov-2 Omicron Variants, Jimin Lee, James Brett Case, Young-Jun Park, Rashmi Ravichandran, Daniel Asarnow, M Alejandra Tortorici, Jack T Brown, Shilpa Sanapala, Lauren Carter, David Baker, Michael S Diamond, David Veesler

2020-Current year OA Pubs

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits broadly neutralizing activity of SARS-CoV-2 variants and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered intranasally post-exposure. The resistance of TRI2-2 to viral escape by most variants and the ability to deliver it directly to the upper airways highlight the potential of the multivalent …

Flipi24: A Modern Prognostic Model And Clinical Trial Enrichment Tool For Newly Diagnosed Follicular Lymphoma, Matthew J Maurer, Vit K Prochazka, Tarec Christoffer El-Galaly, Christopher R Flowers, Diego Villa, Emmanuel Bachy, Elliot J Cahn, Marguerite Fournier, Melissa C Larson, Caroline E Dietrich, Lasse Hjort Jakobsen, Hervé Ghesquières, Robert Kridel, Maher K Gandhi, Chan Y Cheah, Eliza A Hawkes, John F Seymour, Ciara L Freeman, Michael R Clausen, Björn E Wahlin, Jonathan W Friedberg, Carla Casulo, Thomas M Habermann, Yucai Wang, Loretta J Nastoupil, Peter De Nully Brown, David Belada, Andrea Janíková, Heidi Mocikova, Tomáš Fürst, Pierre Feugier, Hervé Tilly, Corinne Haioun, Andrew J Davies, Guillaume Cartron, Richard Burack, Dai Chihara, Peter Martin, Jonathon B Cohen, Izidore S Lossos, Brad S Kahl, Laurie H Sehn, Karin E Smedby, Gilles Salles, Marek Trneny, Brian K Link, Franck Morschhauser, James R Cerhan

Faculty, Staff and Student Publications

Purpose: Although most patients with follicular lymphoma (FL) can expect an indolent course, progressive lymphoma remains the primary cause of death during the first decade after diagnosis. Progression of disease within 24 months (POD24) of starting first-line (1L) immunochemotherapy defines a high-risk population with poor survival, but better risk stratification at diagnosis is needed.

Methods: The FLIPI24 model was developed and internally validated to predict 24-month event rates using individual data from 4,485 patients treated with 1L immunochemotherapy from 10 observational cohorts of FL. Overall and cause-specific survival was further evaluated in FLIPI24 risk groups. External validation in the 1L …

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 …

Daily Locomotor Activity Declines With Tumor Growth And Disease Progression In Glioblastoma, Maria F Gonzalez-Aponte, Sofia V Salvatore, Anna R. Damato, Ruth Gn Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog

2020-Current year OA Pubs

Glioblastoma (GBM) is an aggressive brain tumor that often progresses despite resection and treatment. Timely and continuous assessment of GBM progression is critical to expedite secondary surgery or enrollment in clinical trials. However, current progression detection requires costly and specialized MRI examinations, which, in the absence of new symptoms or signs, are usually scheduled every 2-3 months. Here, we hypothesized that changes in daily activity are associated with GBM growth and disease progression. We found that wheel-running activity in GBM-bearing mice declined as tumors grew and preceded weight loss and circadian breakdown by over a week. Temozolomide treatment in the …

Ga4gh Phenopacket-Driven Characterization Of Genotype-Phenotype Correlations In Mendelian Disorders., Lauren Rekerle, Daniel Danis, Filip Rehburg, Adam S L Graefe, Viktor Bily, Andrés Caballero-Oteyza, Pilar Cacheiro, Leonardo Chimirri, Jessica X Chong, Evan Connelly, Bert B A De Vries, Alexander J M Dingemans, Michael H Duyzend, Tomas Freiberger, Petra Gehle, Tudor Groza, Peter Hansen, Julius O B Jacobsen, Adam Klocperk, Markus S Ladewig, Michael I Love, Allison J Marcello, Alexander Mordhorst, Monica C Munoz-Torres, Justin Reese, Catharina Schuetz, Damian Smedley, Timmy Strauss, Ondrej Vladyka, David Zocche, Sylvia Thun, Christopher J Mungall, Melissa A Haendel, Peter N Robinson

Faculty Research 2026

Comprehensively characterizing genotype-phenotype correlations (GPCs) in Mendelian disease would create new opportunities for improving clinical management and understanding disease biology. However, heterogeneous approaches to data sharing, reuse, and analysis have hindered progress in the field. We developed Genotype-Phenotype Statistical Evaluation of Associations (GPSEA), a software package that leverages the Global Alliance for Genomics and Health (GA4GH) Phenopacket Schema to represent case-level clinical and genetic data about individuals. GPSEA applies an independent filtering strategy to boost statistical power to detect categorical GPCs represented by Human Phenotype Ontology terms. GPSEA additionally enables visualization and analysis of continuous phenotypes, clinical severity scores, and …

Gh Alters Lymphatic Vessels In Female Mice And Stat5 Phosphorylation In Human Lymphatic Endothelial Cells, Christopher Walsh, Emily Scott, Elise Wagner, Jerome Walsh, Shashank Reddy, Arshad Ahmad, Reetobrata Basu, Eva Sevick-Muraca, Rich Brody, Uday Sandbhor, Sebastian Neggers, John J Kopchick

The Brown Foundation: Institute of Molecular Medicine

Disruption of lymphatic function underlies a broad spectrum of inflammatory and metabolic disorders, yet the hormonal pathways that regulate lymphatic biology remain poorly defined. GH, which is implicated in similar disease states, has an unclear role in lymphatic homeostasis. To address this gap, we investigated how chronic alterations in GH signaling alter lymphatic structure and function. Using transgenic mouse lines with increased, decreased, or absent GH action, we quantified the effect of GH on lymphatic pumping rate and lymphangiogenic remodeling during wound healing using near-infrared fluorescent imaging. We also measured markers of lymphatic endothelial cells using Western blot and immunohistochemistry …

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 …

Pathways, Outputs And Impact Of Nih-Supported Bioinformatics And Genomics Graduate Trainees In Africa, Daudi Jjingo, Andrew Walakira, Suhaila Hashim, Cisse Cheickna, Ronald Galiwango, Caleb Kibet, Florence N Kivunike, Gerald Mboowa, Fredrick Elishama Kakembo, Babajide Ayodele, Jean-Baka Domelevo Entfellner, Santie De Villiers, Karen Wambui, Segun Fatumo, Tinashe Chikowore, John Mukisa, Alfred Ssekagiri, Nicholas Bbosa, Julius Mulindwa, Samuel Kyobe, Mike Nsubuga, Grace Kebirungi, Eric Katagirya, Savannah Mwesigwa, Ibra Lujumba, Rogers Kamulegeya, Samuel Kirimunda, Stephen Kanyerezi, Shahiid Kiyaga, Ivan Sserwadda, Davis Kiberu, Bernard S Bagaya, Julius Okwir, Patricia Nabisubi, Grace Nabakooza, Mugume Twinamatsiko Atwine, Ricard Sserunjogi, Rolanda Julius, Mariam Quiñones, Meghan Mccarthy, Phillip Cruz, Karlynn Noble, Christopher J Whalen, Darrell Hurt, Maria Y Giovanni, Michael Tartakovsky, Deogratius Ssemwanga, John M Kitayimbwa, Steven J Reynolds, Christopher C Whalen, Andrew Kambugu, Neil A Hanchard, Li Jian, Peter Amoako-Yirenkyi, Graeme Mardon, I King Jordan, Samson Pandam Salifu, Mamadou Wele, Ezekiel Adebiyi, Jeffrey G Shaffer, Seydou Doumbia, David Patrick Kateete, Michelle Skelton, Nicola Mulder, Jonathan K Kayondo, Daniel Masiga, H3africa Consortium

Faculty, Staff and Students Publications

Global biomedical and health research is increasingly relying on genomic and computational approaches, largely driven by the increasing volumes of nucleic acid sequencing. Concurrently, epidemiological studies and clinical records are generating enormous amounts of data amenable to disease modeling, machine learning, and artificial intelligence techniques. Bioinformatics and data science expertise is therefore essential for improved population health. Accordingly, in 2012, the US National Institutes of Health (NIH) in partnership with the Wellcome Trust, and with support from the African Society for Human Genetics, initiated the H3Africa (Human Heredity and Health in Africa) consortium. One of its key goals was to …

Bayesian Multi-Cell Type Models For The Analysis Of Complex Immune Cell Populations With Application To Ovarian Cancer., Chase J. Sakitis, Jose Laborde, Julia Wrobel, Alex C. Soupir, Christelle M. Colin-Leitzinger, Benjamin G. Bitler, Mary K. Townsend, Andrew B. Lawson, Joellen M. Schildkraut, Shelley S. Tworoger, Kathryn L. Terry, Lauren C. Peres, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

To understand how the tumor immune microenvironment (TIME) impacts clinical outcomes and treatment response, researchers have been leveraging single-cell protein multiplex imaging techniques. These technologies measure multiple protein markers simultaneously within a tissue sample, providing a more complete assessment of the TIME. However, statistical challenges arise from the over-dispersed and zero-inflated nature of the data and from relationships among different immune cell populations. To address these challenges, we developed a Bayesian hierarchical method using a beta-binomial (BB) distribution to model the abundance of multiple immune cell types simultaneously while incorporating relationships and immune cell differentiation paths. We applied the model …

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 …