Digital Commons Network^™

Demographic And Clinicopathologic Factors Associated With Colorectal Adenoma Recurrence, Usman Ayub Awan, Qingyuan Song, Kristen K Ciombor, Adetunji T Toriola, Jungyoon Choi, Timothy Su, Xiao-Ou Shu, Kamran Idrees, Kay M Washington, Wei Zheng, Wanqing Wen, Zhijun Yin, Xingyi Guo

2020-Current year OA Pubs

IMPORTANCE: Current colorectal surveillance guidelines emphasize adenoma characteristics but overlook temporal, racial, and sex-based heterogeneity in recurrence risk, a gap that limits equitable and personalized care.

OBJECTIVE: To evaluate the associations of demographic factors, obesity, and adenoma features with recurrence risk over time in a large longitudinal surveillance cohort.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included adults who underwent their first colonoscopic polypectomy between January 1990 and July 2024 at a tertiary medical center.

EXPOSURES: Demographic variables included race and ethnicity, sex, obesity (body mass index >30), family history of colorectal cancer (CRC) or polyps, and age at …

Amyloidosis Of Bridging Veins Is A Pathologic Feature Of Alzheimer's Disease, Leon C D Smyth, Daan Verhaege, Elio Standen-Bloom, Yue Wu, Steffen E Storck, Pavle Boskovic, Benjamin A Plog, Tornike Mamuladze, Jose A Mazzitelli, Zhuoying Wang, Daniel D Lee, Gwendalyn J Randolph, Katherine E Schwetye, Song Hu, Jonathan Kipnis, Et Al.

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by the accumulation of extracellular aggregated amyloid beta, resulting from impaired waste clearance. We recently identified new cerebrospinal fluid (CSF) efflux structures termed arachnoid cuff exit (ACE) points and speculated that these may be impacted in AD, leading to impaired waste clearance function. Using 5XFAD mice, we found progressive amyloidosis of bridging veins at ACE points. Indeed, in 5XFAD mice, there is impaired CSF efflux to the dura mater, impaired CSF flow along bridging veins, and impaired blood flow through bridging veins. These observations suggest that ACE point amyloidosis plays a role in waste clearance …

Scper: A Rigorous Computational Approach To Determine Cellular Subtypes In Tumors Aligned With Cancer Phenotypes From Total Rna Sequencing, Bingrui Li, Xiaobo Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Single-cell RNA sequencing (scRNA-seq) is a powerful technique for understanding cellular diversity, but processing large patient cohorts to identify phenotype-associated cell populations remains challenging. Here, scPER (Estimating cell Proportions using single-cell RNA-seq Reference), a rigorous approach combining adversarial autoencoder and extreme gradient boosting to estimate tumor microenvironment cell compositions and identify phenotype-associated subclusters for bulk RNA-seq samples. Integrating scRNA-seq datasets from diverse studies, scPER constructed comprehensive reference panels and disentangled confounders from true signals. scPER achieved superior accuracy in cellular proportion estimation compared to CIBERSORTx, BayesPrism, Scaden, MuSiC, SCDC, DeSide and ReCIDE. It showed high accuracy in predicting metastatic melanoma …

Physics-Informed Self-Supervised Diagnosis Of Rotating Machinery Using Latent Odes And Transformer Encoders, Md Al Amin, Mohammad Shafat Ahsan, Jannatul Maua, Mumtahina Ahmed, Kamruddin Nur

Student Publications [Scholarly]

This paper proposes a novel Physics-Informed Self-Supervised Diagnosis (PI-SSD) framework for rotating machinery fault detection, combining physical modeling, self-supervised representation learning, and uncertainty-aware classification. The architecture integrates a multi-resolution convolutional encoder, a windowed Transformer for temporal context modeling, and a latent neural ordinary differential equation (ODE) module that embeds mechanical priors, such as Jeffcott rotor dynamics, directly into the learning process. A masked segment reconstruction objective enables self-supervised pretraining using unlabeled healthy signals, while an evidential classifier head produces fault probabilities with calibrated uncertainty. We evaluate PI-SSD on two publicly available datasets, the NASA PHM’09 Gearbox dataset and the Aalto …

Volumetric Buccal Bone Alterations At Immediate Implant Sites With Or Without Soft Tissue Augmentation: A 6-Month Assessment, Mary Jung, Duong Tran, Chi-Ching Chang, Sung K Kim, Yosuke Tsukiboshi, Seiko Min, Srinivas Ayilavarapu, Chun-Teh Lee

Faculty, Staff and Student Publications

Background: This study is part of a randomized controlled trial investigating the impact of soft tissue augmentation (STA) using subepithelial connective tissue graft (SCTG) (immediate implant with subepithelial connective tissue graft [ICT] group) or acellular dermal matrix (ADM) (immediate implant with acellular dermal matrix [IAD] group) versus no STA (control) on the clinical outcomes following immediate implant placement (IIP). This study aimed to investigate volumetric buccal bone dimensional changes at immediate implant sites 6 months after the surgery.

Methods: Forty-five patients requiring extraction of a maxillary anterior tooth or premolar and randomly assigned to one of the three groups were …

Markvcid2 Consortium For Clinical Validation Of Biomarkers Of Cerebral Small Vessel Disease: Validation Framework And Baseline Characteristics, Steven M Greenberg, Marylin S Albert, Hongyu An, Konstantinos Arfanakis, Arnold M Evia, Arvind Caprihan, Andria L Ford, Myriam Fornage, Gregory S Day, Jason D Hinman, Gregory A Jicha, Amir H Kashani, Joel H Kramer, Christian Lachner, Jin-Moo Lee, Peiying Liu, Hanzhang Lu, Pauline Maillard, Ronald C Petersen, Bruce M Psaty, John M Ringman, Gary A Rosenberg, Claudia L Satizabal, Sean I Savitz, Julie A Schneider, Sudha Seshadri, Prashanthi Vemuri, Danny J J Wang, Donna M Wilcock, B Gwen Windham, Rong Zhang, Carissa Tuozzo, Herpreet Singh, Sue Moy, Vilma Okey-Ewurum, Courtney B Page, Hillary Mulder, Pia Kivisäkk, Deborah Blacker, Lidiya Mazina, Karl G Helmer, Kristin Schwab, Lisa M Wruck, Roderick A Corriveau

Faculty, Staff and Student Publications

Objective: To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework.

Methods: Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD-related cognitive decline was estimated primarily by …

A Systemic Selective Modified Mrna Delivery Platform For Preventing Chemotherapy-Induced Cardiotoxicity, Jimeen Yoo, Mengcheng Shen, Et Al.

2020-Current year OA Pubs

Doxorubicin (Dox) is a widely employed chemotherapeutic agent, but its use is clinically limited by dose-accumulative cardiotoxicity. More specifically, Dox induces oxidative stress and causes pro-apoptotic ceramide accumulation in cardiomyocytes (CMs). Acid ceramidase (AC) modified mRNA (modRNA) has been shown to reduce ceramide levels and protect the heart following ischemic injury; however, therapeutic modRNA applications have been hindered by the need for invasive delivery. Here, we present a platform for minimally intrusive transmission of modRNA to the heart. This CM-selective modRNA translational system (cmSMRTs) is encapsulated in lipid nanoparticles for intravenous (IV) delivery to enable systemic administration with high cardiac …

A Step-By-Step Guide To Performing Cancer Metabolism Research Using Custom-Made Media, Sophie Seifert, Francisco Yanqui-Rivera, Tim Kühn, Lena Elise Høyland, Toman Borteçen, Bella Agranovich, Lara Elea Eckhardt, Martin Herdt, Alessa Henneberg, Verena Panitz, Faisal Hayat, Marie Migaud, Gernot Poschet, Ifat Abramovich, Eyal Gottlieb, Jeroen Krijgsveld, Mathias Ziegler, Mirja Tamara Prentzell, Christiane A Opitz

Faculty, Staff and Student Publications

The preparation of custom-made media offers precise control over nutrient composition, enabling detailed studies of cellular metabolism. We demonstrate how self-made media formulations enable diverse assay designs and readouts to assess cancer metabolism. Self-made media can be used in Seahorse assays to measure mitochondrial respiration under defined conditions. In nutrient deprivation experiments, amino acid or vitamin removal can uncover how cancer cells adapt to metabolic stress. Using labeled amino acids enables analysis of nascent protein synthesis and translational regulation, while stable-isotope tracing reveals metabolic fluxes through key pathways. This guide presents a suite of metabolic assays using custom-made media, covering …

Leveraging Large Language Models For Heuristic Usability Assessment Of Medical Software: Insights With The Radiation Planning Assistant, Laurence E Court, Jacobus Smit, Lourens Strauss, William Shaw, Andrea Marais, Christoph Trauernicht, Nanette Joubert, Elaine Smith, Shona Badre, Graeme L Lazarus, Thekiso Khotle, Lauren Netherton, Wanda Van Heerden, Carlos Cardenas, Monica Serban, Jan Seuntjens, Christine V Chung, Pavel Govyadinov, Meena Khan, Saurabh Nair, Tucker Netherton, Lifei Zhang

Faculty, Staff and Student Publications

Background: Usability engineering is essential for ensuring the safety and effectiveness of medical software, as design-related issues are a leading cause of use errors in clinical settings. Heuristic evaluation provides a practical approach to identifying usability problems, but its outcomes depend heavily on expert interpretation. Large Language Models (LLMs), such as ChatGPT, offer a potential means to augment heuristic evaluation by generating structured, context-aware usability feedback. This study explored the use of ChatGPT to support heuristic assessment of the Radiation Planning Assistant (RPA), a web-based radiotherapy planning tool designed to support clinical teams in low- and middle-income countries.

Methods: ChatGPT …

Convolutional Neural Networks For Automatic Tuber Segmentation And Quantification Of Tuber Burden In Tuberous Sclerosis Complex, Iván Sánchez Fernández, Matheus D Soldatelli, Gillian N Miller, Catharina F Gout, Ellen C Broekhuizen, Iris C J Den Hertog, Daan A Pijs, Errol Apostolopoulos, Prabhjot Kaur, Abdelhakim Ouaalam, Martina E Bebin, Hope Northrup, Darcy A Krueger, Joyce Y Wu, Alexander L Cohen, Mustafa Sahin, Davood Karimi, Simon K Warfield, Jurriaan M Peters

Faculty, Staff and Student Publications

Objective: This study was undertaken to develop a fully automated algorithm for tuber segmentation and quantification of tuber volume that performs similarly to the gold standard human neuroradiologist.

Methods: We used brain magnetic resonance imaging (MRI) from patients with tuberous sclerosis complex (TSC) to train and validate a convolutional neural network (CNN), which was evaluated on segmentation with the Dice-Sørensen similarity coefficient (DSSC) and on tuber burden quantification with Spearman correlation coefficient against a neuroradiologist's gold standard in the test set.

Results: We collected 263 MRIs from 196 patients (57% males) with median (25th percentile-75th percentile) age of 4.3 (3.0-10.1) …

Presenilin L166p Mutation, A Model Of Familial Alzheimer's Disease, Leads To Early Onset Bone Loss, Vidyani Suryadevara, Connor J Krehbial, Anuradha K Valiya, Melinda Vang, Julian Balanta-Melo, Pierre P Eleniste, Sumana Posritong, Jung Min Hong, Katie Chester, Gabriel M Pagnotti, Teresita Bellido, Monte S Willis, Angela Bruzzaniti

Faculty, Staff and Student Publications

Accelerated bone loss has been reported in the early stages of Alzheimer's disease (AD) as indicated by reduced bone mineral density and increased fracture risk in these patients, compared to healthy individuals. In the present study, we investigated bone loss in mouse models of familial Alzheimer's disease harboring the Presenilin 1 (L166P) knock-in mutation (PSEN1 KI), with or without the human amyloid precursor protein transgene (hAPP Tg+) known to induce brain amyloid pathology by 6 months. Female and not male 12-month PSEN1/hAPP Tg+ mice exhibited reduced whole-body bone mineral density and bone mineral content, compared to sex-matched controls. Consistent with …

Decellularized Extracellular Matrix Scaffolds To Engineer The Dormant Landscape Of Microscopic Colorectal Cancer Liver Metastasis, Sabrina N Vandenheuvel, Lucia L Nash, Abigail J Clevenger, Claudia A Collier, Oscar R Benavides, Sanjana Roy, Brinlee Goggans, Aelita Salikhova, Anvitha Tharakesh, Svasti Haricharan, Amber N Stratman, Scott Kopetz, Alex J Walsh, Shreya A Raghavan

Faculty, Staff and Student Publications

Recurrent liver-metastatic colorectal cancer contributes to high mortality. Recurrence occurs when dormant, microscopic residual disease survives initial treatment to escape dormancy. In their dormant, microscopic state within the liver, these metastatic lesions are undetectable by clinical diagnostic imaging until they form overt, chemoresistant metastases. Therefore, understanding the molecular mechanisms underlying dormancy in colorectal cancer liver metastases is a significant knowledge gap, motivating the engineering of nuanced in vitro models of disease. The current work presents an engineered model of liver-metastatic colorectal cancer dormancy. Decellularized extracellular matrix (dECM) scaffolds are used to provide microscopic colorectal cancer cell clusters with a biomimetic, …

Quantitative Analysis Of Robustness-Based Versus Let-Based Optimization In Intensity-Modulated Proton Therapy For Pediatric Brain Tumors, Fariha Kabir Torsha, Gino Lim, Hadis Moazami Goudarzi, Radhe Mohan, David Grosshans, Wenhua Cao

Faculty, Staff and Student Publications

Purpose: To perform a quantitative analysis of the trade-off between robustness-based and linear energy transfer (LET)-based optimization of intensity-modulated proton therapy for anatomically challenging pediatric brain tumor cases.

Methods: Three pediatric brain tumor patients were included in this study. Three plans were generated for each case based on: (1) nominal optimization, without considering uncertainties and LET; (2) robust optimization, including proton range and patient setup uncertainties; and (3) LET optimization, considering increasing LET in the target and reducing LET in normal tissues. All plans were optimized with individually fine-tuned objective weighing to obtain highest achievable target coverage and meet dose …

Apea: A Type 1 Diabetes Self-Management Ambient-Ai Assistance Tool That Bridges Trajectory Prediction, Interactive Explanation, And Just-In-Time Adaptive Intervention Action., Kun-Yi Chen, Erin M. Tallon, Chi-Ren Shyu

Manuscripts, Articles, Book Chapters and Other Papers

Helping patients self-managing diseases like type 1 diabetes (T1D) requires informatics tools delivering real-time predictions with explainable, actionable guidance. However, many healthcare AI solutions lack actionable recommendations and user-friendly explanations, limiting clinical impacts. We introduce APEA, a pediatric T1D self-management Ambient-AI assistance tool, integrating glucose multi-trajectory-scenarios Prediction, interactive, context-aware large language model Explanations, and just-in-time adaptive intervention policy optimization for Actionable real-time suggestions through reinforcement learning. Using T1DEXIP dataset (262 pediatric T1D patients, multi-center), our results showed improved glucose control outcomes: 45% over human management, 69% over infusion-pump management. Although constrained by small sample size and …

Rethinking The Centrality Of Brain Areas In Understanding Functional Organization, Benjamin Yost Hayden, Sarah R Heilbronner, Seng Bum Michael Yoo

Faculty, Staff and Students Publications

Parcellation of the cerebral cortex into functionally modular brain areas is foundational to cognitive and systems neuroscience. Here, we question the central status of brain areas from the perspectives of neuroanatomy and electrophysiology. We argue that the major ostensible determinants of brain function, such as cytoarchitecture and connectivity, seldom produce convergent parcellations. Brain areas themselves are just one of several equally important organizing principles; others include macroscale gradients, distributed networks, layers, columns and patches. We further argue that the evidence for a close correspondence between areal parcellation and cognitive function is weaker than is generally supposed. Indeed, many important cognitive …

Deep Brain Stimulation Response Circuits In Obsessive-Compulsive Disorder, Andreas Horn, Ningfei Li, Garance M Meyer, Ron Gadot, Nicole R Provenza, Sameer A Sheth

Faculty, Staff and Students Publications

In the field of deep brain stimulation (DBS), two major themes are currently making significant progress. First, the framework of connectomic DBS, in which circuits that are associated with improvements of specific symptoms are described and targeted to improve and potentially personalize treatment. Second, the concept of brain sensing and adaptive DBS, which aims at identifying neural biomarkers that may guide stimulation in a closed-loop fashion.

In DBS for Obsessive Compulsive Disorder (OCD), substantial progress has been made on both ends, over the last five years. Together, results begin to draw a picture of exactly which circuit is …

Single-Cell Atlas Of The Transcriptome And Chromatin Accessibility In The Human Retina, Jin Li, Jun Wang, Ignacio L Ibarra, Xuesen Cheng, Malte D Luecken, Jiaxiong Lu, Aboozar Monavarfeshani, Wenjun Yan, Yiqiao Zheng, Zhen Zuo, Samantha Lynn Zayas Colborn, Berenice Sarahi Cortez, Leah A Owen, Brittney Wick, Xuan Bao, Jongsu Choi, Maximilian Haeussler, Nicholas M Tran, Karthik Shekhar, Joshua R Sanes, J Timothy Stout, Shiming Chen, Yumei Li, Margaret M Deangelis, Fabian J Theis, Rui Chen

Faculty, Staff and Students Publications

Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here we present an integrated dual-modal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 3.9 million cells from 125 donors of diverse ancestral backgrounds, including 8 published studies and 2.7 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) with more than 130 cell types identified. We annotated each cluster, identified marker genes and characterized cis-regulatory elements and gene regulatory networks. Our analysis uncovered differences in transcriptome, chromatin and gene regulatory …

In-Silico Trial Of Same-Day Simulation-Free Spatially Fractionated Adaptive Radiotherapy (Sf2-Art), Dennis N Stanley, Alyssa R Birchmeier, Carlos E Cardenas, Richard A Popple, Natalie Viscariello, Joel A Pogue, Courtney B Stanley, Mehran Yusuf, Michael Soike, Samuel R Marcrom, Joseph Harms

2020-Current year OA Pubs

PURPOSE: Here we present an in-silico trial of the feasibility and deliverability of a same-day, simulation-free workflow for spatially fractionated adaptive radiotherapy (SF

METHODS AND MATERIALS: Ten patients (five thoracic and five extremity), previously treated with spatially fractionated radiotherapy (SFRT), were selected for this in silico trial. A two-phase regimen was simulated: Phase 1 delivered 12 Gy SBRT to a uniform, predefined high-dose lattice and 4 Gy to the gross tumor volume (GTV); Phase 2 consisted of 4 additional fractions of 4 Gy to the GTV. The planning workflow was performed entirely in silico, without the need for CT simulation. …

Phase 1 Study Of Inbrx-105, A Tnfrsf9 (4-1bb) And Pd-L1 Bispecific Antibody, In Patients With Select Solid Tumors, Jong Chul Park, Doug R Adkins, Et Al.

2020-Current year OA Pubs

PURPOSE: INBRX-105, a tetravalent, PD-L1-targeted TNFRSF9 (4-1BB) agonist, demonstrated preclinical antitumor activity. This first-in-human study evaluated INBRX-105 in solid tumors.

PATIENTS AND METHODS: This open-label, 4-part, phase 1 study evaluated INBRX-105 alone or with pembrolizumab in adults with locally advanced/metastatic, unresectable solid tumors (NCT03809624). INBRX-105 was administered intravenously once every 2 weeks or 4 weeks in parts 1 (single-agent dose escalation; 0.001-3 mg/kg) and 2 (single-agent expansion) or once every 3 weeks in parts 3 (combination dose escalation; INBRX-105 0.03-1.0 mg/kg) and 4 (combination expansion). Part 2 enrolled patients with checkpoint inhibitor-relapsed/refractory (CPI-R/R) tumors. Part 4 enrolled patients with CPI-R/R …

The Origin Of Hepatocellular Carcinoma Depends On Metabolic Zonation, Jason Guo, Roger Liang, Andrew Chung, Zhijie Li, Boyuan Li, Eric Chen, Lin Li, Jingjing Wang, Meng-Hsiung Hsieh, Ivy Xiangyi Fang, Benjamin Kroger, Yunguan Wang, Min Zhu, Xiongzhao Ren, Greg Mannino, Yuemeng Jia, Yonglong Wei, Stephen Moore, Daniel J Siegwart, Stephen S Chung, Zixi Wang, Tripti Sharma, Suman Komjeti, Yi Han, Purva Gopal, Guanghua Xiao, Tao Wang, Hao Zhu

Faculty, Staff and Student Publications

The origin of cancer is poorly understood because premalignant cells are rarely followed in their native environments. Although the spatial compartmentalization of metabolic functions is critical for proper liver function, it is unknown whether cancers arise from some zones but not others and whether there are metabolic determinants of cancer risk. Zone-specific, mosaic introduction of Ctnnb1 (catenin beta 1) and Arid2 (AT-rich interaction domain 2) mutations, commonly co-mutated genes in hepatocellular carcinoma (HCC), in mouse models showed that position and metabolic context determine clone fates. Ctnnb1/Arid2-driven cancers were much more likely to arise in zone 3. The …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Differentiation In The Human Urothelia Is Defined By Distinct Alternative Polyadenylation, Ninh B Le, Surbhi Sona, Briana Santo, Yi Zhang, Rosie Ou, R Allen Schweickart, Veena Kochat, William I Padron, Kunal Rai, Shih-Han Lee, Joo Mi Yi, Oliver Wessely, Byron H Lee, Angela H Ting

Faculty, Staff and Student Publications

Distinct epithelial cell states arise during differentiation, but mechanisms generating transcriptomic diversity among them remain poorly defined. The human ureter urothelium contains basal progenitor, intermediate cells, and terminally differentiated umbrella cells. Prior single-cell RNA sequencing revealed similar global gene expression profiles across these states, raising the question of how distinct identities emerge. Here, we show that alternative cleavage and polyadenylation (APA) introduces a major layer of transcriptomic diversity during urothelial differentiation, largely independent of changes in mRNA levels. Analysis of 13,544 urothelial cells identified hundreds of differentiation-associated APA events. Single-cell imaging revealed spatially specific APA patterns, and reporter assays demonstrated …

Cxcr4 Induces Memory Formation Over Exhaustion In Car-T Cells To Achieve Durable Leukemia Targeting., Ari Itoh-Nakadai, Minggao Liang, Michiho Shindo, Chen Bibi, Mariko Tomizawa-Murasawa, Saera Fujiki, Akiko Kaneko, Emi Kanamaru, Mari Hashimoto, Hiroshi Kajita, Yoshinari Ando, Miki Kojima, Jonathan Moody, Makoto Iwasaki, Shinsuke Takagi, Ryo Nakagawa, Saumya Agrawal, Hanae Amitani-Iijima, Kaori Sato, Yuriko Sorimachi, Nahoko Suzuki, Takehiro Fukami, Kazuharu Hanada, Satoshi Morita, Kazushige Katsura, Takehisa Matsumoto, Maiko Kobayashi, Masahiko Kato, Yasuyuki Negishi, Mikako Shirouzu, Yuho Najima, Keiyo Takubo, Chung Chau Hon, Naoyuki Uchida, Shuichi Taniguchi, Yukihide Momozawa, Piero Carninci, Leonard D. Shultz, Yoriko Saito, Michiel De Hoon, Jay W Shin, Fumihiko Ishikawa

Faculty Research 2026

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the formation of long-lived memory T cells, whereas T cell exhaustion contributes to non-response and relapse. In patients with AML who achieved remission after cord blood transplantation, we here first observe enrichment of memory T cells with high expression of the chemokine receptor CXCR4. Next, we show that engineering CAR-T cells to co-express CXCR4 enhances their persistence and anti-leukemic activity in patient-derived xenograft models. Using single-cell profiling and metabolic analysis, we find that …

Early Detection Of Bladder Cancer Using Advanced Feature Engineering And Swarm Intelligence Optimization On Ehrs, Xu Wang, Andrea Preston, Jonathan Aning, Michael Loizou, Shang-Ming Zhou

School of Nursing and Midwifery

Background: Bladder cancer (BC) symptoms often overlap with benign conditions, while no routine screening exists for general population. We aim to develop a machine learning (ML)-based screening pipeline for early BC detection using electronic-health-records (EHRs) in primary care. Methods: A multi-centred case-control cohort (1995–2018; n = 64,884) was created for model training and testing. We further validated the model prospectively on an independent cohort (2019–2020; n = 4,569). We proposed the Parsimony driven REweighting for Calibrated Input-based Screening for Early detection—Adjustable Grey Zone (PRECISE-AGZ), which identified influential features from 48,261 candidates and developed a calibrated logistic regression screening model with …

Ionic Mechanisms Of Two-Pore Channel Regulation Of Vesicle Trafficking, Heng Zhang, Michael X Zhu

Faculty, Staff and Student Publications

The endolysosomal system plays a pivotal role in cellular function. Before reaching lysosomes for degradation, the endocytosed cargoes are sorted at various stages of endosomal trafficking for recycling and/or rerouting. The proper execution of these processes depends on tightly regulated ion fluxes across endolysosomal membranes. Recent studies have demonstrated the importance of two-pore channels (TPCs), including TPC1 and TPC2, in endolysosomal trafficking. These channels are expressed in the membranes of distinct populations of endosomes and lysosomes, where they respond to nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to conduct Ca2+ and Na+ release from these acidic organelles. …

Simulated Complex Cells Contribute To Object Recognition Through Representational Untangling, Mitchell B Slapik, Harel Z Shouval

Faculty, Staff and Student Publications

The visual system performs a remarkable feat: it takes complex retinal activation patterns and decodes them for object recognition. This operation, termed "representational untangling," organizes neural representations by clustering similar objects together while separating different categories of objects. While representational untangling is usually associated with higher-order visual areas like the inferior temporal cortex, it remains unclear how the early visual system contributes to this process-whether through highly selective neurons or high-dimensional population codes. This article investigates how a computational model of early vision contributes to representational untangling. Using a computational visual hierarchy and two different data sets consisting of numerals …

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 …

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 …

Medulloblastoma Stem Cell Programs: Molecular Roadmaps Of Disease Progression, Jamie Zagozewski, Parthiv Haldipur, Kathleen J Millen, Tamra E Werbowetski-Ogilvie

Faculty, Staff and Students Publications

Over the last decade, an unprecedented number of sequencing studies have characterized the molecular landscape of pediatric brain cancers, including the highly heterogeneous tumor medulloblastoma (MB). Extensive MB profiling has enabled a much deeper understanding of the primitive neurodevelopmental programs that are hijacked during tumor progression. However, we have yet to successfully target and fully eradicate the putative stem and early progenitor cells that drive MB tumorigenesis. This goal will require better human models that faithfully recapitulate oncogenic events, a deeper understanding of the mechanisms governing cell fate decisions in the primary and metastatic compartments, and comprehensive validation studies of …