Digital Commons Network^™

Optimizing Human Fcrn Mouse Models To Improve Pharmacokinetic Evaluation Of Antibody Drug Candidates., Gregory J. Christianson, Zachary M Howard, Samantha Kenney, Emily Lowell, Nijaguna Bethur, Derry C. Roopenian, Elena Gonzalo-Gil

Faculty Research 2026

The use of animal models that can reliably predict drug performance in human patients is critical to antibody therapeutic development. Along with assessing toxicity and efficacy, determining the pharmacokinetic (PK) properties of therapeutics in Tg32 and Tg276 mice is essential to preclinical characterization. While Tg32 mice have been well established as indispensable in their ability to model the PK properties of antibody therapeutics, their intact immunity leaves them capable of mounting anti-drug antibody responses that interfere with PK interpretation. Here, we demonstrate the negative impact anti-drug responses can have on PK parameters derived from Tg32 mice, and provide strong evidence …

Optimizing Human Fcrn Mouse Models To Improve Pharmacokinetic Evaluation Of Antibody Drug Candidates., Gregory J. Christianson, Zachary M Howard, Samantha Kenney, Emily Lowell, Nijaguna Bethur, Derry C. Roopenian, Elena Gonzalo-Gil

Faculty Research 2026

The use of animal models that can reliably predict drug performance in human patients is critical to antibody therapeutic development. Along with assessing toxicity and efficacy, determining the pharmacokinetic (PK) properties of therapeutics in Tg32 and Tg276 mice is essential to preclinical characterization. While Tg32 mice have been well established as indispensable in their ability to model the PK properties of antibody therapeutics, their intact immunity leaves them capable of mounting anti-drug antibody responses that interfere with PK interpretation. Here, we demonstrate the negative impact anti-drug responses can have on PK parameters derived from Tg32 mice, and provide strong evidence …

Limosilactobacillus Reuteri Promotes Melatonin Release From Human Intestinal Organoids Via 5′Ectonucleotidase Activity, Micah D Forshee, Erika J Nachman, Esha R Shenoy, Heather A Danhof, Ludwig Ermann Lundberg, Stefan Roos, Robert A Britton

Faculty, Staff and Students Publications

Strains of Limosilactobacillus reuteri have been used to prevent or treat various conditions; however, the mechanisms by which they exert beneficial effects are not completely understood. Infant colic is one example in which L. reuteri DSM 17938 reduces clinical symptoms. While the etiology of colic is unknown, abnormal melatonin levels in infants have been suggested as a possible contributor. L. reuteri DSM 17938 has been shown to produce adenosine from AMP via production of the extracellular enzyme 5′ectonucleotidase (5′NT). Adenosine is a potent signaling molecule that impacts several important aspects of host physiology, including the release of melatonin from the …

Using Randomization To Compare Ai And Expert-Generated Formative Assessment Questions In Medical Education, Akshat Kumar, Katie Stinson, Litao Wang, Elizabeth Nugent, Yongsu Lee, Mark Hormann, Latanya Jones Love, Toufeeq Ahmed Syed

Faculty, Staff and Student Publications

Background: AI-generated content is being used across the education spectrum and is beneficial for creating complex multiple-choice questions, such as those used in medical education. However, evaluating AI-generated content is challenging, and existing testing and evaluation methods are falling short. This study uses randomization to compare medical students' performance on and subjective evaluation of AI versus expert-generated questions. We hypothesized that there would be no difference in student performance or subjective evaluation of AI vs expert-generated questions.

Methods: We designed a single-center, randomized study where medical student participants received either one AI- or expert-generated question per day over four weeks. …

Steroid Receptor Coactivator 3-Deficient Regulatory T Cells Eradicate Multiple Solid Tumors In Syngeneic Mouse Models, Nuri Sung, Eunsu Kim, Yosef Gilad, Yuri Park, Adam M Dean, Yan Xia, Jianming Xu, Clifford C Dacso, David M Lonard, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is highly expressed in regulatory T cells (Tregs) and is important for their immunosuppressive activity. Recently, we demonstrated that disrupting SRC-3 expression in Tregs eliminates triple-negative breast cancer (TNBC) and prostate cancer in syngeneic animal models by generating an anti-tumor immune microenvironment without inducing immune-related adverse events (irAEs). Further analysis of these mice revealed that SRC-3 knockout (KO) Tregs infiltrated breast tumors and facilitated the infiltration of CD8

Mtorc2-Nav1.2 Signaling Drives Early Hyperexcitability In Alzheimer’S Disease Mouse Model, Nolan M Dvorak, Jeffrey L Noebels

Faculty, Staff and Students Publications

Hyperexcitability is a biomarker of early-stage Alzheimer’s Disease (AD) and hastens cognitive decline later in its course. Mechanistic target of rapamycin (mTOR) signaling contributes to the slope of this trajectory, as evidenced by early increased brain expression and the rescue of hyperexcitability by genetic deletion of mTOR complex 2 (mTORC2); however, a molecular mechanism directly linking mTOR signaling to membrane hyperexcitability in early-stage AD remains elusive. Here, we show that hyperactive mTOR signaling stimulates the voltage-gated Na+ channel 1.2 (Nav1.2), a previously identified downstream phosphorylation target of mTORC2 and a key regulator of membrane electrogenesis. Augmented Nav1.2 channel function induced …

Application Of Hi-C Sequencing To Detect Oncogene Rearrangements For Diagnosis And Treatment Of Large B-Cell Lymphoma., Zijun Y. Xu-Monette, Chang Wang, Dehong Wu, Alexandar Tzankov, Michael B. Møller, Carlo Visco, Eric D. Hsi, Xiaoxian Zhao, Beibei Lv, Bangchen Wang, Xin Cao, Shuna Yao, April Chiu, Karen Dybkaer, Govind Bhagat, Youli Zu, Santiago Montes-Moreno, Zenggang Pan, Leon Bernal-Mizrachi, J Han Van Krieken, William Choi, Wayne Tam, Weina Chen, Maurilio Ponzoni, Andrés J M Ferreri, Benjamin M. Parsons, Farzaneh Khajouei, Kristin Sikkink, Yong Li, Alex R. Hastie, Anthony D. Schmitt, Ken H. Young

Manuscripts, Articles, Book Chapters and Other Papers

Diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, arises from various pathogenic mechanisms, including gene translocations and fusions. Detection of gene rearrangements using fluorescence in situ hybridization (FISH) is a standard practice for DLBCL diagnosis and guides treatment decisions. High-throughput chromosome conformation capture (Hi-C) DNA sequencing is a next-generation sequencing-based technology to identify genome-wide rearrangements using a single assay. In this study, Hi-C sequencing was performed using formalin-fixed paraffin-embedded tissues from 159 patients with DLBCL, identifying 746 cancer genes at or proximal to the rearrangement breakpoints, with a total of 1903 occurrences. Focusing on clinically important rearrangements, …

Artificial Intelligence, Machine Learning, And Deep Learning Approaches For Attention-Deficit/Hyperactivity Disorder Diagnosis: Protocol For A Scoping Review, Benedict Onochie Ibe, Amir Aly, Shaymaa S Al-Juboori, Emmanuel Ifeachor, Rohit Shankar

School of Engineering, Computing and Mathematics

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) affects over 366 million adults and 139 million children worldwide, yet diagnosis remains fundamentally subjective, relying on clinical interviews, behavioral observations, and rating scales that yield inconsistent results across practitioners and settings. Artificial intelligence (AI), machine learning (ML), and deep learning (DL) offer a paradigm shift toward objective, data-driven diagnosis by detecting complex patterns across neuroimaging, electrophysiology, and digital biomarkers that elude conventional assessment. Although AI-based ADHD research has grown exponentially, no comprehensive synthesis examines the full spectrum of data modalities, validation practices, and clinical translation readiness. This gap limits our understanding of which approaches are …

Early Prediction Of The Breast Cancer Response To Neoadjuvant Chemotherapy Based On Intratumoral Interstitial Fluid Pressure Using 3-D Subharmonic-Aided Pressure Estimation, Sung In Choi, Basak Dogan, Corinne E. Wessner, Jessica H. Porembka, Priscilla Machado, B. Bersu Ozcan, Nisha Unni, Maysa Abu-Khalaf, Kenneth Hoyt, Flemming Forsberg, Kibo Nam

Department of Radiology Faculty Papers

Elevated intratumoral interstitial fluid pressure (IFP) may negatively impact the efficacy of neoadjuvant chemotherapy (NAC). This study aimed to predict the breast cancer response to NAC based on intratumoral IFP using 3D contrast-enhanced ultrasound (CEUS) with subharmonic-aided pressure estimation (SHAPE). This prospective study enrolled breast cancer patients undergoing NAC from two clinical sites. 3D CEUS was performed at 0%, 10%, and 30% of NAC completion using a GE Logiq E9 with Definity. The pressure gradients between the tumor and adjacent normal tissue were estimated by SHAPE, utilizing the inverse linear relationship between the ultrasound contrast agent’s subharmonic signal amplitude and …

Unveiling Functional-Metabolic Synergy In The Healthy Brain: Multivariate Integration Of Dynamic [18f]Fdg-Pet And Resting-State Fmri, Claudia Tarricone, Giulia Vallini, Giorgia Baron, Massimiliano Facca, Erica Silvestri, Tommaso Volpi, Andrei G Vlassenko, Manu S Goyal, Alessandra Bertoldo

2020-Current year OA Pubs

Despite accounting for only 2% of body weight, the human brain requires significant amounts of glucose, even at rest, underscoring the importance of functional-metabolic relationships. Previous studies revealed moderate associations between resting-state fMRI functional connectivity (FC) and local metabolism via [

Agentic Ai For Clinical Outcomes Research, Population Health Management Analyses With Large Administrative Databases, And Generating Epidemiological Estimates Of Diseases: Feasibility And Validation Study, Daniel Frisch, Michael Fronstin, Carla Zema

Division of Cardiology Faculty Papers

BACKGROUND: There is tremendous enthusiasm for the use of AI in health care because of the ability to analyze existing data for preventative, diagnostic, and treatment support. Agentic AI can feasibly provide access to large real-world datasets for the generation of real-world evidence for health care and clinical applications to health care providers, researchers, and administrators without access to large analytic programming resources.

OBJECTIVE: The objective of this study was to understand the feasibility of using agentic AI for clinical outcome research and population health management. Specifically, this study used an agentic AI evidence-generation platform to obtain epidemiological estimates of …

Interface Geometry Governs Probe Insertion Mechanics And Electrode Deviation In Layered Brain-Mimicking Phantoms For Deep Brain Stimulation, Siyu Chen, Chengyuan Wu, Ethan Anders, Rungun Nathan, Olivia M. Bailey, Qifu Wang, Curtis L. Johnson, Qianhong Wu

Department of Neurosurgery Faculty Papers

Parkinson's disease (PD) is a progressive neurological disorder often treated with Deep Brain Stimulation (DBS), a surgical procedure that involves implanting electrodes to improve motor function. Accurate electrode placement is critical for treatment efficacy but can be influenced by tissue deformation, insertion forces, and the mechanical properties of brain tissue. In this study, we investigated the role of layer interface angle as a controlled biomechanical factor affecting insertion forces and electrode deviation. A two-layer agar gel phantom was constructed to produce a prescribed stiffness transition between a lower-stiffness and a higher-stiffness gel layer, and its small-amplitude dynamic shear-stiffness contrast was …

Assessment Of Timp1, Transgelin-2, And Procalcitonin As Protein Biomarkers For Diagnosis And Prognosis Of Bloodstream Infection In A Critically Ill Cohort, Sajal Tiwary, Caroline A O'Neil, Sydney Lawless, Olivia Arter, Meghan Brown, Brittany Roemmich, Carleigh Samuels, Jennie H Kwon, Christopher W Farnsworth

2020-Current year OA Pubs

BACKGROUND: Bloodstream infections (BSI) are a significant contributor to morbidity and mortality among hospitalized patients. Rapid diagnosis of BSI is critical for timely and appropriate clinical management, but current diagnostic strategies have a prolonged turnaround time or only identify select pathogens with minimal prognostic information.

METHODS: We examined serial serologic samples from 77 intensive care unit (ICU) patients at time points before, during, and after diagnosis of presumptive BSI to identify host-derived protein biomarkers associated with specific organisms and with clinical outcomes in BSI. ICU patients with and without BSI were included. Two candidate biomarkers, tissue metalloproteinase 1 (TIMP-1) and …

Artificial Intelligence Models For Automated And Semiautomated Analysis And Interpretation Of Clinical Electroencephalography, Sándor Beniczky, Birgit Frauscher, Fábio Nascimento, Shobi Sivathamboo, Catalina Rojas, Michael Sperling, Samden Lhatoo, Philippe Ryvlin, Levin Kuhlmann

Department of Neurology Faculty Papers

Electroencephalography is the most commonly used diagnostic tool for epilepsy. However, interpreting electroencephalograms (EEGs) requires expertise that is not widely available. Advances in digital technology and wearables have enabled large-scale EEG recording, generating vast amounts of data that cannot be managed through traditional visual interpretation by experts. Artificial intelligence (AI) has the potential to augment human expertise and reduce workloads. The application of artificial neural networks in analysing clinical EEG recordings has led to major breakthroughs, bringing AI-based EEG interpretation closer to clinical implementation. In this Review, we summarise the most important research and development results in this field from …

Skin Carotenoid Scores Are A Valid Approximation Of Fruit And Vegetable Intake Among Adults With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Elizabeth Gates, Melissa N Laska, Andrew R Dinardo, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoid score (SCS) as measured using pressure-mediated reflection spectroscopy has been validated among adults with normal and overweight body mass index, with little validation research among adults with obesity. Therefore, the purpose of this exploratory study was to examine the validity of SCS as an approximation of fruit and vegetable intake among adults with obesity. We used samples from adults with obesity from three prior studies: The first study examined the validity of SCS among 213 adults, 34 with obesity; the second, examined sensitivity of SCS to a β-carotene-rich juice intervention among 162 adults, 14 with obesity; the third …

Inosine-Triphosphate-Pyrophosphatase Activity As A Potential Predictor Of Methotrexate Remission In Juvenile Idiopathic Arthritis., Sofia Sindici Forgiarini, Marianna Lucafò, Debora Curci, Davide Selvestrel, Valentina Moressa, Sofia Pagarin, Barbara Bellich, Martina Franzin, Alberto Tommasini, Mara L. Becker, Laura Ramsey, Susan D. Thompson, Carl D. Langefeld, Federica Corba, Edoardo Marrani, Gabriele Simonini, Gabriele Stocco, Giuliana Decorti, Andrea Taddio, Serena Pastore

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Methotrexate (MTX) is the first-line therapy for juvenile idiopathic arthritis (JIA), but up to 40% of patients do not respond to it. Low inosine triphosphate pyrophosphatase (ITPA) activity has been associated with reduced clinical remission. We investigated the role and underlying mechanisms of ITPA in vitro.

METHODS: ITPA enzymatic activity was measured by high-performance liquid chromatography with ultraviolet detection in erythrocyte lysates from patients with JIA (enrolled in Trieste, Italy; Florence, Italy; and Kansas City, Missouri) receiving weekly MTX (10-15 mg/m²) for at least 12 months. Remission was evaluated by Wallace et al criteria. ITPA rs1127354, which …

The Rise And Fall Of Lateral Electrical Surface Stimulation (Less) Through The Lens Of Srs Archives., Ali Rezazadeh Shirazi, Jay I. Kumar, Katie Dold, George H. Thompson, Andrew G. King, Richard M. Schwend, John P. Lubicky, Jay Shapiro, Behrooz A. Akbarnia, History Committee Of The Scoliosis Research Society

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Lateral electrical surface stimulation (LESS), commercially known as the ScoliTron™, emerged in the late 1970s as a noninvasive alternative to bracing for adolescent idiopathic scoliosis. Early clinical reports generated considerable enthusiasm and adoption, but the technique was ultimately abandoned. This study examined the rise and fall of LESS through a combined analysis of the Scoliosis Research Society (SRS) archives and published literature, with the goal of understanding factors that influence the adoption, evaluation, and abandonment of innovation in scoliosis care.

METHODS: A structured historical review was conducted using archival materials from the Scoliosis Research Society (SRS), including meeting abstracts, …

Patient-Specific Computational Fluid Dynamics Modeling Of Airway Collapse In Infants With Robin Sequence., Gautam Jalori, Michael Barbour, Michael Bindschadler, Kelly Evans, John P. Dahl, Alberto Aliseda

Manuscripts, Articles, Book Chapters and Other Papers

Robin Sequence (RS) is a congenital condition in which patients experience dynamic, periodic obstruction or collapse of the upper airway due to an underdeveloped jaw and a posteriorly displaced tongue. Current clinical techniques for evaluating airway obstruction do not provide quantifiable data and fail to account for the dynamic nature of obstruction or collapse. There is no standardized criterion to characterize obstruction or collapse severity. This study presents the first method that extracts airway motion from 4-dimensional computed tomography and performs a patient-specific, moving-mesh computational fluid dynamics (CFD) analysis of RS patients with complete airway collapse or obstruction. To quantify …

Spinal Cord Imaging For Multiple Sclerosis: Advances, Priorities, And Opportunities, Cornelia Laule, Matthew R Brier, Et Al.

2020-Current year OA Pubs

The spinal cord plays a central role in the pathophysiology and clinical manifestations of multiple sclerosis (MS), yet remains under-studied compared with the brain. This review summarizes key insights from the 2025 North American Imaging in MS Spinal Cord Imaging Workshop, highlighting recent advances, ongoing challenges, and future opportunities in MS spinal cord imaging. We review pathological studies and outline the clinical relevance of spinal cord lesions and atrophy for diagnosis, prognosis, and disease monitoring, highlighting emerging biomarkers of progression independent of relapse activity. Correlations between magnetic resonance imaging, histopathology, and clinical outcomes support the validation and translational potential of …

Towards Human-Centered Digital Health Interventions, Kristin M Kostick-Quenet, Eric A Storch

Center for Medical Ethics and Health Policy Staff Publications

This article discusses the potential of digital health interventions (DHIs) in mental health care, emphasizing the importance of designing them to foster genuine humanistic care. It highlights current challenges in measuring engagement and outcomes, advocating for integrating human-centered endpoints such as dignity, autonomy, and therapeutic alliance into evaluation frameworks. The authors call for mechanistic research to identify effective engagement strategies and context-specific implementation approaches. Ultimately, successful DHIs should demonstrate both clinical efficacy and the preservation of humane, person-centered care, ensuring ethical and meaningful mental health support through technology.

Real-World Testing Of An Artificial Intelligence Conversational Agent As An Early Intervention And Support Tool In The Mental Health Referral Care Pathway: A Mixed-Methods Study, Rohit Shankar, Edward Meinert, Madison Milne-Ives, Emma Taylor, B Inkster, Alina Paik, Ananya Ananthakrishnan, Martin Orr, Ceire Costelloe

Peninsula Medical School

Background: The incidence of mental health concerns is growing, and demand for support is exceeding service capacity.Digital tools can provide additional support but risk causing harm if not delivered safely.Aims: We aimed to establish real-world evidence of the impact of an artificial intelligence-based mental healthconversational agent (Wysa) on depression and anxiety in patients waiting for Talking Therapies treatment.Methods: A mixed-methods randomized controlled trial was conducted with patients referred to Talking Therapies inthe Central and Northwest London NHS Foundation Trust. The primary outcome was change in depression severityover 12weeks between groups; secondary outcomes included anxiety severity, quality of life, safety, engagement, …

Crosstalk Between Upr And Mitochondria: The Triad Of Er-Mitochondria Contacts, Ca²⁺, And Ros, Ester Zito, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum (ER) stress is triggered by several cellular perturbations causing protein misfolding, and activates the unfolded protein response (UPR), an initially adaptive signaling network that aims to restore ER and cellular homeostasis. Growing evidence indicates that UPR signaling extends beyond ER proteostasis, influencing mitochondrial function and bioenergetics through ER-mitochondria contact sites (ERMCs). The CHOP-ERO1A-IP3R axis has a primary role in recruiting mitochondria to adaptive UPR. However, its sustained activation renders UPR signaling maladaptive, leading to mitochondrial dysfunction through both outer mitochondrial membrane permeabilization (OMMP) and mitochondrial permeability transition pore (mPTP) opening, ultimately contributing to irreversible cell injury and disease …

Compbio And Miras-A Multi-Omic Analysis Platform Built On A Memory-Based Intelligence Engine, Ruteja A Barve, Chad E Storer, Wayne D Hoxsie, Curtis Marcum, Joshua F Mcmichael, Jared M Lalmansingh, Brittany K Smith, Mark R Johnson, Daniel J Kuster, Richard D Head

2020-Current year OA Pubs

As molecular and cellular technologies have advanced, the need to analyze and interpret the resulting vast and multi-modal data into actionable intelligence has become a rate-limiting factor in scientific advancement. While traditional knowledgebase-pathway tools and LLM-based AI tools provide a degree of support in data interpretation, both exhibit known limitations. Presented here is the CompBio multi-omic analysis platform built upon Memory-based Intelligent Reasoning System (MIRaS), an associative reasoning engine grounded in episodic and semantic memory, capable of inferring biological relationships directly from stored knowledge rather than from model training. The MIRaS system is not dependent on human-curated pathway knowledgebases, provides …

Cells And Networks In Flux: Rethinking Ontogenesis And Pathogenesis, Mark L. Tykocinski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Organ and tissue functions emerge from the coordinated activity of cell networks. Therapeutics that act on pathogenic cell networks, modulating their cellular interplay, follow naturally. Over several decades, our laboratory has developed a series of approaches for rewiring cell networks, culminating in a class of cell surface-directed signal converter proteins (SCPs) that do so by modulating juxtacrine and autocrine signaling in and among their nodal cells. A first such SCP has now produced encouraging clinical data for cancer immunotherapy. Yet, these early network-directed fusion proteins rest on a deliberately simplified picture: discrete end-cell types plugged into graphically tractable networks. That …

Implementation Readiness For National Cancer Survivorship Care Standards, Christiane J. El Khoury, Meera Gupta, Maryem Shirzadi, Heidi Dowst, Martha Mims, Maysa Abu-Khalaf, Hoda Badr

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Cancer survivorship care is a growing public health priority, yet delivery remains variable across health systems. The National Standards for Cancer Survivorship Care provide a framework for high-quality care, but little empirical evidence exists regarding health system readiness to implement these standards in routine practice.

OBJECTIVE: To assess implementation readiness for the National Standards for Cancer Survivorship Care and identify perceived barriers to implementation.

DESIGN, SETTING, AND PARTICIPANTS: This real-time Delphi survey study was conducted from January to March 2025 at a National Cancer Institute-designated comprehensive cancer center. Participants were multidisciplinary experts involved in cancer survivorship care delivery, care …

Immune Reconstitution And Tolerance-Inducing Therapies As Promising Therapeutic Approaches In Multiple Sclerosis, Alireza Beheshti Maal, Mandana Kazem Arki, Seyed Massood Nabavi, Mostafa Rezaei-Tavirani, Elham Rismani, Massoud Vosough, Gholamreza Azizi, Nikoo Hossein-Khannazer

Department of Neurology Faculty Papers

OBJECTIVES: Multiple sclerosis (MS) is a complex, progressive neurodegenerative autoimmune disease and a major cause of neurological disability worldwide. MS affects approximately 2.8-3 million people, predominantly presenting as relapsing-remitting MS (RRMS) that frequently converts to secondary progressive disease, while effective options for progressive phenotypes remain limited.

METHODS: This review reframes MS immunotherapy through a tolerance-centric paradigm, distinguishing continuous maintenance disease-modifying therapies (DMTs) from immune reconstitution therapies (IRTs) and emerging antigen-specific tolerance strategies.

RESULTS: Classical immune reconstitution therapies, including alemtuzumab, cladribine, and autologous hematopoietic stem cell transplantation (aHSCT), have demonstrated durable disease control and prolonged periods of no evidence of disease …

7th International Workshop On Sox Transcription Factors., Aya Uchida

Faculty Research 2026

Marking the 20th anniversary of a well-established meeting series focused on the biological and clinical importance of SOX genes as regulators of cell fate, the 7th International Workshop on SOX Transcription Factors held from 8-11 September 2025 at the Prince Resort MICE Karuizawa in Nagano, Japan, brought together 83 participants from 17 countries. The meeting showcased the foundations of SOX gene research and recent technological and conceptual breakthroughs across diverse model systems and human research, illustrating the field's evolution and emerging directions for future research. Reflecting the breadth of SOX biology - from early embryonic development and sex determination to …

Digital Markers For Passive Remote Monitoring Of Bipolar Disorder: Systematic Review, Thomas P Kutcher, Isha Chakraborty, Kristin Kostick-Quenet, Akane Sano, Nidal Moukaddam, Jeffrey A Herron, Wayne K Goodman, Sameer A Sheth, Ashutosh Sabharwal, Nicole R Provenza

Duncan NRI Faculty and Staff Publications

Background: Bipolar disorder (BD) features episodic shifts among mania, hypomania, depression, mixed states, and euthymia. Timely detection of mood transitions is difficult due to infrequent clinical touchpoints. Digital health technologies, including wearables and smartphones, offer a unique opportunity to passively and continuously monitor behavior and physiology that could reflect underlying mood dynamics in real-world settings.

Objective: This study aimed to systematically review passively collected digital markers for BD mood states, characterize devices/modalities and analytic approaches, appraise risk of bias, and identify design gaps and priorities for clinical translation.

Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) …

Translational Reading Frame Predicts The Pathogenicity Of C-Terminal Frameshift Deletions In Mecp2, Jacky Guy, Elena Hein, Beatrice Alexander-Howden, Timur Von Bock Und Polach, Tricia Mathieson, Benjamin P Kleinstiver, Huda Y Zoghbi, Adrian Bird

Duncan NRI Faculty and Staff Publications

Mutations in the MECP2 gene cause the severe neurological disorder Rett syndrome. A cluster of frameshift-causing C-terminal deletions (CTDs) removes ~100 amino acids and accounts for approximately 10% of RTT-causing mutations. Their pathogenicity is unexpected because this C-terminal domain is dispensable in mice. Analysis of pathogenic and benign human MECP2 variants reveals that some individuals with apparently typical CTDs do not develop Rett syndrome, confirming that C-terminal truncations are not intrinsically pathogenic. Using human sequence data and mouse models we show that pathogenicity results from a marked reduction in MeCP2 levels and depends on the presence of a proline proline …

Malt1 Protease Inhibition Restrains Glioblastoma Progression By Reversing Tumor-Associated Macrophage-Dependent Immunosuppression In Mice, Juliana Hofstätter Azambuja, Saigopalakrishna Yerneni, Lisa Maurer, Hannah Crentsil, Gabriela Debom, Linda Klei, Mei Smyers, Chaim Sneiderman, Kristina Schwab, Rajesh Acharya, Aivi Nguyen, Josie Emery, John Little, Jeffrey Meridew, Yijen Lin Wu, Prasanna Ekambaram, Dong Hu, Pete Gough, John Bertin, Ari Melnick, Gary Kohanbash, Riyue Bao, Peter Lucas, Linda Mcallister-Lucas

College of Life Sciences Faculty Papers

MALT1 protease is an intracellular signaling molecule that promotes tumor progression via cancer cell-intrinsic and cancer cell-extrinsic mechanisms. MALT1 has been mostly studied in lymphocytes, and little is known about its role in tumor-associated macrophages. We show that MALT1 is expressed in glioblastoma (GBM)-associated macrophages. Mechanistically, GBM tumor cells induce a MALT1-NF-κB signaling axis in macrophages, leading to enhanced macrophage migration and polarization toward an immunosuppressive ('M2-like') phenotype. Inactivation of MALT1 protease promotes transcriptional reprogramming that reduces migration and restores a macrophage anti-tumor 'M1-like' phenotype. Preclinical in vivo analysis shows that MALT1 inhibitor treatment results in immuno-reactivity of GBM-associated macrophages …