Digital Commons Network^™

Rare But Relevant? Assessing Variants In Dystonia-Linked Genes In Parkinson's Disease, Lara M Lange, Zih-Hua Fang, Laurel Screven, Ai Huey Tan, Roy N Alcalay, Rim Amouri, Roberta Bovenzi, Matilda Fenn, Joshua L I Frost, Joseph Jankovic, Simona Jasaityte, Zane Jaunmuktane, Beomseok Jeon, Ignacio Juan Keller Sarmiento, Rejko Krüger, Gregor Kuhlenbäumer, Chin-Hsien Lin, Lukas Pavelka, Maria Teresa Periñan, Samia Ben Sassi, Tommaso Schirinzi, Jung Hwan Shin, Joshua M Shulman, Yi Wen Tay, Ryan Uitti, Tom Warner, Zbigniew K Wszolek, Lesley Wu, Ruey-Meei Wu, Kirsten E Zeuner, Cornelis Blauwendraat, Andrew Singleton, Niccolò E Mencacci, Huw R Morris, Shen-Yang Lim, Katja Lohmann, Christine Klein

Faculty, Staff and Students Publications

Background: Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear.

Objective: The aim was to assess the frequency of dystonia-linked pathogenic variants in PD.

Methods: We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) for variants in genes linked to isolated dystonia, dystonia-parkinsonism, and myoclonus-dystonia.

Results: Pathogenic variants were identified only in PD patients. Forty-five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia-linked genes, most …

Highly Variable Expressivity Of A Cnv Deletion Involving Tbx4 In Three Deceased Siblings With Lung Developmental Disorder And Their Mildly Affected Mother And Grandfather, Przemyslaw Szafranski, Tomasz Gambin, Michal Kadlof, Michał Denkiewicz, Dariusz Plewczynski, Hyun Jeong Kim, Gail Deutsch, Nahir Cortes-Santiago, Salmo Raskin, Paweł Stankiewicz

Faculty, Staff and Students Publications

Single nucleotide variants (SNVs) and copy-number variant (CNV) deletions involving TBX4 have been associated with pulmonary arterial hypertension, ischiocoxopodopatellar syndrome, and lethal lung developmental disorders (LLDDs). Thus far, all large CNV deletions encompassing entire TBX4 have been found to have arisen de novo. Here, we present a three-generation family with three neonate siblings who died within 35-66 days due to histopathologically diagnosed LLDD. Whole-genome sequencing identified an ~108-kb CNV deletion encompassing TBX4 in all three infants. The deletion was also found in their mother with a history of pneumonia and persistent thick upper airway secretions and in the maternal grandfather …

A Nonlinear Relationship Of Evoked Responses Following Charge-Balanced Single-Pulse Electrical Stimulation With Varying Pulse Widths, Isabel A Danstrom, Joshua A Adkinson, Zoe Liu, Meghan E Robinson, Denise Oswalt, Garrett P Banks, Atul Maheshwari, Lu Lin, Ben Shofty, Mohammed Hasen, Alica Goldman, Eleonora Bartoli, Sarah R Heilbronner, Kelly R Bijanki

Faculty, Staff and Students Publications

Background: Single-pulse electrical stimulation (SPES) can help guide neuromodulation therapy in an iterative process to reveal ideal circuits and degrees of engagement. Understanding the relationship between parameter input and neural output will be necessary both to build informative models of the brain's functional connectivity and to improve responses to stimulation-based neuromodulation therapies. Modulating pulse width alters the total charge delivered to neural tissue and is thought to selectively activate fibers with different diameters, potentially shifting therapeutic thresholds. The anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) are of great clinical relevance to the pathophysiology and treatment of neuropsychiatric disorders.

Objective: …

Suicidal Ideation In Spinocerebellar Ataxia, Levi Peppel, Ruo-Yah Lai, Christian Rummey, Puneet Opal, Jeremy D Schmahmann, Christopher M Gomez, Henry Paulson, Theresa A Zesiewicz, Susan Perlman, George Wilmot, Sarah H Ying, Chiadi U Onyike, Khalaf O Bushara, Michael D Geschwind, Karla P Figueroa, Stefan M Pulst, Sub H Subramony, Antoine Duquette, Tetsuo Ashizawa, Ali G Hamedani, Marie Y Davis, Sharan R Srinivasan, Matthew R Burns, Nadia Amokrane, Lauren R Moore, Vikram G Shakkottai, Liana S Rosenthal, Sheng-Han Kuo, Chi-Ying R Lin

Faculty, Staff and Students Publications

Objective: Suicidal ideation has not been extensively studied in spinocerebellar ataxias (SCAs). The authors examined whether individuals with SCAs have increased suicidal ideation and related factors.

Methods: The authors studied patients with genetically confirmed SCAs enrolled in the Clinical Research Consortium for the Study of Cerebellar Ataxia cohort, examining the percentages of patients with SCA subtypes 1, 2, 3, and 6 who reported suicidal ideation and comparing findings with nationally representative data from the National Survey on Drug Use and Health (NSDUH). Clinical characteristics that may contribute to suicidal ideation in SCAs, including age, disease duration, sex, ataxia severity, depression, …

Strategies And Challenges For The Recruitment Of Young Healthy Participants In The Dietary Approaches To Longevity And Health (Dial Health) Pilot Trial, Hannah E Cabre, Courtney M Peterson, Gareth R Dutton, Kimberly L Drews, Stephanie T Broyles, Robert Dubin, Laura Q Rogers, Catherine Champagne, Dennis T Villareal, Daniel S Hsia, Leanne M Redman, Corby K Martin

Faculty, Staff and Students Publications

Background: Understanding the impact of nutrition on human aging requires long-term trials in young, healthy, unmedicated adults. As part of the Dietary Approaches for Longevity and Health (DiAL Health) pilot project, we evaluated strategies for recruiting this population for aging-related dietary intervention studies.

Methods: We analyzed recruitment costs to enroll 70 participants (ages 25-49, BMI 22.0-29.9 kg/m2) across two DiAL Health sites and used NHANES data (2017-March 2020) to estimate the proportion of U.S. adults meeting partial trial eligibility. Additionally, a formative study surveyed 492 U.S. adults (≥18 years) to assess interest in aging-focused dietary trials.

Results: Of 2049 applicants …

Differences In Gene Expression May Contribute To The Racial Differences In The Risk Of Masld, Ivan P Gorlov, Olga Y Gorlova, Aaron P Thrift

Faculty, Staff and Students Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), exhibits marked racial disparities in incidence, progression, and clinical outcomes. While diet, lifestyle, and socioeconomic factors have been shown to influence these disparities, biological mechanisms underlying racial differences in MASLD risk remain poorly understood. We hypothesized that race-associated variation in hepatic gene expression may contribute to differential susceptibility and progression of MASLD. To test this hypothesis, we analyzed publicly available gene expression data from liver biopsies obtained from over 300 Black and White individuals undergoing bariatric surgery. Gene expression profiles were compared across four histological stages: …

Sewers To Solutions: A Guide To Wastewater Pathogen Monitoring, Justin R Clark, Anthony W Maresso

Faculty, Staff and Students Publications

Wastewater-based epidemiology (WBE) is the analysis of wastewater to detect pathogen levels or activity for public health awareness or action. Pioneered in the 1940s, WBE underwent a resurgence during the COVID-19 pandemic, providing important information about number of cases, outbreaks, and seasonal impact. With advancements in detection technologies and growing interest in environmental surveillance, WBE is poised to become a standard practice in public health monitoring. Here, we provide an overview of the current state of the art of pathogen WBE, including methods of molecular detection, analysis of wastewater data, real-world applications and programs, public health interventions, and benefits and …

Common And Recurrent Dysregulated Molecular Network Of Placental Hypoxia And Associated Vasculogenesis And Angiogenesis In Fetal Growth Restriction, Wei Li, Xiaoyi Bai, Oi Ka Chan, Maran Bo Wah Leung, So Ling Lau, Chi Chiu Wang, Tak Yeung Leung

Faculty, Staff and Students Publications

Fetuses with fetal growth restriction (FGR) and selective FGR (sFGR) face elevated health risks both before and after birth. Although the underlying pathomechanisms remain unclear, placental dysfunction is recognized as a major contributing factor. By integrating untargeted transcriptomic data from FGR/sFGR placentae, this study identified 69 differentially expressed mRNAs (DEmRs) and eight differentially expressed miRNAs (DEmiRs). Functional enrichment analysis demonstrated significant enrichment in the angiogenesis and vasculogenesis pathways, with the hypoxia-related genes

Pd-L1-Centric Whole Blood-Based Immune Signature Profiles Of Tuberculosis Patients During Therapy, Johanna Eggeling, Martina Sester, Christoph Lange, Jan Heyckendorf, Barbara Kalsdorf, Anna M Mandalakas, Andrew R Dinardo, David Lewinsohn, Dagmar Schaub, Tina Schmidt, Eva Tolosa, Maja Reimann, Patricia M Sánchez Carballo

Faculty, Staff and Students Publications

This prospective study investigated whole blood-based immune cell biomarkers for pulmonary tuberculosis (TB) immunoprofiling. Blood samples from 34 healthy controls and 51 tuberculosis patients were analyzed at three timepoints: Prior to therapy (T0), after 14 days of therapy (T1), and at the end of treatment (Te). Using multiparameter flow cytometry, 386 immune cell populations were analyzed. Predictive models were developed using two machine learning algorithms. A TB5LF change score, which was based on five cell populations, effectively distinguished tuberculosis patients from controls (AUC = 0.89) and tuberculosis patients before and at the end of treatment (AUC = 0.92). Similarly, the …

Gut Microbiome Metagenomics In Clinical Practice: Bridging The Gap Between Research And Precision Medicine, Henok Ayalew Tegegne, Tor C Savidge

Faculty, Staff and Students Publications

Gut microbiome metagenomics is emerging as a cornerstone of precision medicine, offering exceptional opportunities for improved diagnostics, risk stratification, and therapeutic development. Advances in high-throughput sequencing have uncovered robust microbial signatures linked to infectious, inflammatory, metabolic, and neoplastic diseases. Clinical applications now include pathogen detection, antimicrobial resistance profiling, microbiota-based therapies, and enterotype-guided patient stratification. However, translation into routine care is hindered by significant barriers including methodological variability, limited functional annotation, lack of bioinformatics standardization, and underrepresentation of global populations. This review synthesizes current translational strategies, emphasizing the need for hypothesis-driven designs, multi-omic integration, longitudinal and multi-center cohorts, and mechanistic validation. …

Causal Functional Mediation Analysis With An Application To Functional Magnetic Resonance Imaging Data, Yi Zhao, Xi Luo, Michael E Sobel, Martin A Lindquist, Brian S Caffo

Faculty, Staff and Student Publications

A primary goal of task-based functional magnetic resonance imaging (fMRI) studies is to quantify the effective connectivity between brain regions when stimuli are presented. Assessing the dynamics of effective connectivity has attracted increasing attention. Causal mediation analysis serves as a widely implemented tool aiming to delineate the mechanism between task stimuli and brain activations. However, the case, where the treatment, mediator, and outcome are continuous functions, has not been studied. Causal mediation analysis for functional data is considered. Semiparametric functional linear structural equation models are introduced and causal assumptions are discussed. The proposed models allow for the estimation of individual …

Disruption Of Protein-Protein Interaction Hotspots In The C-Terminal Domain Of Mlh1 Confers Mismatch Repair Deficiency, Keri M. Fishwick, Diego Gomez Vieito, Giada Greco, Giulio Collotta, Marco Gatti, Anastasija A. Kulik, Raphaël Guérois, Ivan Corbeski, Ashutosh S. Phadte, Issam Senoussi, Petr Cejka, Anna Pluciennik, Antonio Porro, Alessandro A. Sartori

Department of Biochemistry and Molecular Biology Faculty Papers

MutLα, a heterodimer of MLH1 and PMS2, plays a key role in DNA mismatch repair (MMR), which maintains genomic stability by correcting replication errors. Loss of MLH1 function causes MMR deficiency (MMRd), leading to elevated mutation rates and increased cancer susceptibility. However, MMRd can offer a therapeutic advantage, as high tumour mutational burden enhances the efficacy of immune checkpoint inhibition. MMR also drives somatic expansion of CAG repeats linked to Huntington’s disease (HD) pathogenesis. The C-terminal domain (CTD) of MLH1 contains at least two distinct protein–protein interaction (PPI) sites. The S1 site supports heterodimerization with the PMS2 endonuclease, whereas the …

Speeding Up Interval Estimation For R2-Based Mediation Effect Of High-Dimensional Mediators Via Cross-Fitting, Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei

Faculty, Staff and Student Publications

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed …

Membrane Il-18 Identifies A Human Macrophage Subset With Distinct Proteomic And Functional Traits, Chiara Vitale, Marco Colonna, Et Al.

2020-Current year OA Pubs

This study contributes to the characterization of human macrophages in normal and pathological conditions such as cancer. We characterized a macrophage population expressing membrane-associated IL-18 (mIL-18) that shows peculiar proteomic, phenotypic, ultrastructural, and functional properties. mIL-18+ macrophages exhibit increased levels of key proteins involved in pathogen recognition, activation, migration, and endocytosis. They also display specialized functions in vesicle and actin filament transport and lipid metabolism, and have typical mitochondrial traits. Importantly, mIL-18+ cells dominate the peritoneal fluid of adult cancer patients and are present in the bone marrow of children with neuroblastoma. They express high levels of TREM2 but display …

Nutrition Support Adequacy In Children With Biliary Atresia After Liver Transplant, Nicole Knebusch, Manpreet Virk, Moreshwar S Desai, Marwa Mansour, Stacey Beer, Brittany Pearo, Kelby Fuller, Krupa Mysore, John Goss, Thomas Fogarty, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

No abstract provided.

Mental Health And Beliefs About Abortion Access Following Changes To Reproductive Healthcare Laws In 2022: Findings From Oklahoma, Munjireen Sifat, Laili K. Boozary, Tina N. Le, Julia Mcquoid, Brittany Zaring-Hinkle, Sarah Tonkin, Lizbeth Benson, Bingjing Mao, Motolani Ogunsanya, Ruosi Shao, Amy M. Cohn, Allyson Shortle, Darla E. Kendzor

Department of Medical Oncology Faculty Papers

INTRODUCTION: A secondary analysis of cross-sectional survey data was conducted to characterize beliefs about abortion access in Oklahoma, measure stress associated with the overturn of Roe vs. Wade (2022), and evaluate the potential relationship between post-Roe stress (PR stress) and mental health.

METHODS: From August through September 2022, adult Oklahomans (N = 1793) were surveyed about their sociodemographic characteristics, beliefs about abortion access, frequency of past-month stress related to the overturn of Roe vs. Wade, and mental health. Beliefs about abortion access were characterized overall and within sociodemographic groups. The relationship between PR stress and mental health was evaluated, and …

Dcpr: A Deep Learning Framework For Circadian Phase Reconstruction, Xiao Han, Xiaochen Cen, Zhijin Li, Xiaobo Zhou, Zhiwei Ji

Faculty, Staff and Student Publications

Background: The circadian clock is an evolutionarily conserved system that orchestrates 24-h physiological rhythms through transcriptional and translational feedback loops. Mounting evidence suggests a bidirectional relationship between circadian rhythm alteration and disease progression, positioning the circadian clock as a potential therapeutic target. Due to the scarcity of high-resolution temporal omics data, it remains very challenging to elucidate the underlying regulatory mechanisms of the circadian system. As a practical alternative, public untimed transcriptomic datasets offer the potential to infer gene expression oscillations retrospectively. However, existing computational approaches for circadian phase estimation often suffer from limited predictive accuracy, reducing their ability to …

The Concise Guide To Pharmacology 2025/26: Catalytic Receptors, Stephen P. H. Alexander, Doriano Fabbro, Chloe J. Peach, Alasdair J. Gibb, Eamonn Kelly, Alistair A. Mathie, Emma L. Veale, Jane F. Armstrong, Elena Faccenda, Simon D. Harding, Christopher Southan, Jamie A. Davies, Annie Beuve, Peter Brouckaert, Clare Bryant, John C. Burnett, Richard W. Farndale, Andreas Friebe, John Garthwaite, Adrian J. Hobbs, Gavin E. Jarvis, Laura Kilpatrick, Doris Koesling, Michaela Kuhn, Birgit Leitinger, David Macewan, Tom P. Monie, Lincoln R. Potter, Michael Russwurm, Harald H. H. W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The Concise Guide to Pharmacology 2025/26 marks the seventh edition in this series of biennial publications in the British Journal of Pharmacology. Presented in landscape format, the guide provides a comparative overview of the pharmacology of drug target families. The concise nature of the Concise Guide refers to the style of presentation, being clear, accessible, and well-structured, rather than the scope of the content, which spans approximately 500 pages. The Concise Guide summarises the key pharmacological properties of around 1900 human drug targets, and nearly 7000 interactions, involving around 4400 ligands. While the content is a substantially condensed version of …

A Spatiotemporal Model Of Cxcl10 As A Master Regulator Of Immune Evasion And Metastasis In Osteosarcoma, Benjamin B Gyau, Tsz-Kwong Man

Faculty, Staff and Students Publications

The C-X-C motif chemokine ligand 10 (CXCL10) is implicated in the progression of osteosarcoma (OS), the most aggressive pediatric bone malignancy. However, its role often presents a profound clinical paradox: although high circulating levels are strongly linked to poor prognosis, its canonical function is to recruit anti-tumor immune cells. This review unravels these contrasting roles by proposing a novel spatiotemporal model. We argue that in the early stages, immune-evading OS cells initiate the formation of a pre-metastatic niche (PMN) in the lungs, creating a localized inflammatory environment that becomes the primary source of elevated circulating CXCL10. As the disease progresses, …

Tumor Biology And Access To Care And Metastatic Breast Cancer Outcomes, Matthew R. Dunn, Sarah C. Van Alsten, Marc A. Emerson, Katherine Reeder-Hayes, Terry Hyslop, Melissa A. Troester

Kimmel Cancer Center Faculty Papers

PURPOSE: To understand how access to care influences metastatic breast cancer burden (MBC) while accounting for molecular tumor characteristics, and identify interventions to reduce metastatic disease burden.

METHODS: The Carolina Breast Cancer Study is a population-based cohort with invasive breast cancer (diagnosed 2008-2013). Both de novo metastasis (stage IV at diagnosis) and distant recurrence were evaluated (12 years of follow-up. Tumor data were from medical records, pathology reports, and RNA expression data. Social variables and access to care were from participant surveys. Generalized linear models were used to estimate associations of biological and access characteristics with MBC; Cox models were …

Distinct Populations Of Lung Capillary Endothelial Cells And Their Functional Significance, Joel James, Dan Yi, Zhiyu Dai, Et Al.

2020-Current year OA Pubs

The role of the lung's microcirculation and capillary endothelial cells in normal physiology and the pathobiology of pulmonary diseases is obviously vital. The recent discovery of molecularly distinct aerocytes and general capillary (gCaps) endothelial cells by single-cell transcriptomics (scRNAseq) advanced the field in understanding microcirculatory milieu and cellular communications. However, increasing evidence from different groups indicated the possibility of a more heterogeneous nature of lung capillaries. Therefore, we investigated enriched lung endothelial cells by scRNAseq and identified five novel populations of gCaps with distinct molecular signatures and roles. Our analysis suggests that two major populations of gCaps that express Scn7a(Na

Systemic Sclerosis-Associated Interstitial Lung Disease: Improved Understanding And Advances In Management, Amit Syal, Chris T. Derk

Student Papers, Posters & Projects

Interstitial lung disease (ILD), a common manifestation of systemic sclerosis (SSc), has the highest organ-specific morbidity and mortality, particularly in patients with diffuse cutaneous SSc (dcSSc). Recent advances in diagnostics-including artificial intelligence (AI)-enhanced high-resolution computed tomography (HRCT) and biomarkers such as Krebs van den Lungen (KL)-6-have enabled earlier detection and monitoring of disease progression. Therapeutically, the approval of antifibrotics like nintedanib (NINT) and immunomodulators such as tocilizumab (Toci) has significantly expanded treatment options. Updated international guidelines from the American College of Rheumatology (ACR), American College of Chest Physicians (CHEST), American Thoracic Society (ATS), and European league against Rheumatism (EULAR) now …

Real-World Outcomes Of Talimogene Laherparepvec As Salvage Therapy For Advanced Melanoma, Melissa M Yamada, Smitha Chandrasekhar, Ted A Gooley, Rita E Chen, Coley Doolittle-Amieva, George Ansstas, Shailender Bhatia, Evan T Hall, Paul T Nghiem, Song Y Park, David Y Chen

2020-Current year OA Pubs

BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic herpes simplex virus therapy approved for treatment of unresectable and metastatic melanoma. However, real-world use often occurs in heavily pretreated patients, where evidence of effectiveness remains limited. This study evaluates treatment responses and clinical factors influencing T-VEC outcomes in patients with diverse treatment histories.

METHODS: We analyzed patients with metastatic melanoma treated with T-VEC between 2015 and 2024. Objective responses (OR), complete response (CR) and partial response were assessed using univariate and multivariate Cox regression models. Durability of responses, progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan-Meier estimates.

RESULTS: Among …

Phospholipid Scramblase 1 (Plscr1) Regulates Interferon-Lambda Receptor 1 (Ifn-Λr1) And Ifn-Λ Signaling In Influenza A Virus (Iav) Infection, Alina Xiaoyu Yang, Lisa Ramos-Rodriguez, Parand Sorkhdini, Dongqin Yang, Carmelissa Norbrun, Sonoor Majid, Sanghyun Lee, Yong Zhang, Michael Holtzman, David F Boyd, Yang Zhou

2020-Current year OA Pubs

Phospholipid scramblase 1 (PLSCR1) is an interferon-stimulated gene (ISG) that has several known anti-influenza functions. However, the mechanisms in relation to its expression compartment and enzymatic activity have not been completely explored. Moreover, only limited animal models have been studied to delineate its role at the tissue level in influenza infections. Our results showed that influenza A virus (IAV)-infected

Micu2 Controls Mitochondrial Calcium Signaling And Migration In Neurons During Development, Elena Berezhnaya, Benjamín Cartes-Saavedra, Raghavendra Singh, Macarena Rodríguez-Prados, Orly Reiner, Fowzan S Alkuraya, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Neurological disorders are linked to mitochondrial dysfunction and calcium overload. Mitochondrial calcium uptake is mediated by the mitochondrial calcium uniporter (mtCU), regulated by MICU1, which can be either homodimerized or heterodimerized with MICU2 or MICU3. Though MICU2 is scarce in the adult brain, MICU2 loss in patients leads to a neurodevelopmental disorder. We hypothesized that MICU2 is required for developmental calcium signaling and neuronal migration. MICU2 is present in the developing mouse brain but disappears by maturation, contrasting with other mtCU subunits that increase. MICU2 loss in mice does not affect cytoplasmic calcium but augments the mitochondrial matrix calcium rise …

Perspectives On The Future Of The Profession Of Microbiology, Todd L Kelson, Heidi B Kaplan, Michelle Dziejman, Shilpa Gadwal, Irene Hulede, Jennifer Bennett, Roger Greenwell, Shelley Payne, Kyle Maclea, Eric Miller, Diana L Vullo, Rebecca Sparks-Thissen, Astral Bertolio, Jorge Cervantes

Faculty, Staff and Student Publications

The Profession of Microbiology (POM) embodies the bulk of the American Society for Microbiology (ASM) members and represents the career preparation arm of the ASM for academia, industry, and clinical lab professions. The ASM Council on Microbial Sciences hosted a virtual retreat in 2025 to identify the future of the POM. The retreat presentations centered on workforce development, professional development, innovations in technology, and interdisciplinary collaborations. Various aspects were identified, such as the need to prepare for careers in industry, as an important goal of future training. It was also clear that scientists, in all walks of life, need professional …

Eif3d And Eif3e Mediate Selective Translational Control Of Hypoxia That Can Be Inhibited By Small Molecules, Stephen C Purdy, Kate Matlin, Christopher Alderman, Amber Baldwin, Natasha Shrivastava, Goksu Sarioglu, Somnath Dutta, Kristofor J Webb, Arthur Wolin, Dillon P Boulton, Annika Gustafson, Jyoti Kapali, John D Landua, Michael T Lewis, M Cecilia Caino, James C Costello, William Old, Xiang Wang, Rui Zhao, Heide L Ford, Neelanjan Mukherjee

Faculty, Staff and Students Publications

Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis, effects that are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia-inducible factors (HIFs). However, translational effects in hypoxia, which likely precede transcriptional effects, have remained largely unexplored. Using ribosome profiling, we uncovered a selective translational response in acute hypoxia that is eukaryotic initiation factor (eIF)3d/eIF3e dependent and controls downstream hypoxic responses, including HIF1α accumulation and cellular invasion. We further demonstrated that eIF3e copy number and eIF3e and eIF3d expression signatures are associated with worsened outcomes for patients with breast cancer. Finally, we identified …

Predictive Modeling Of Hematoma Expansion From Non-Contrast Computed Tomography In Spontaneous Intracerebral Hemorrhage Patients, Natasha Ironside, Shinjini Kundu, Et Al.

2020-Current year OA Pubs

Hematoma expansion is a consistent predictor of poor neurological outcome and mortality after spontaneous intracerebral hemorrhage (ICH). An incomplete understanding of its biophysiology has limited early preventative intervention. Transport-based morphometry (TBM) is a mathematical modeling technique that uses a physically meaningful metric to quantify and visualize discriminating image features that are not readily perceptible to the human eye. We hypothesized that TBM could discover relationships between hematoma morphology on initial Non-Contrast Computed Tomography (NCCT) and hematoma expansion. 170 spontaneous ICH patients enrolled in the multi-center international Virtual International Trials of Stroke Archive (VISTA-ICH) with time-series NCCT data were used for …

Pepquerymhc: Rapid And Comprehensive Tumor Antigen Prioritization From Immunopeptidomics Data, Seunghyuk Choi, Bing Zhang

Faculty, Staff and Students Publications

Determining tumor-specificity of MHC-bound peptides is crucial for cancer immunotherapy development, yet current methods struggle with class II peptides and non-reference sequences. We introduce PepQueryMHC, an ultra-fast tool that integrates MHC-bound peptide sequences with translated RNA-seq reads for efficient tumor antigen prioritization. We demonstrate its versatility in prioritizing class I and II tumor antigens, mapping the cellular origins of presented peptides, and resolving uncertainties surrounding the prevalence of proteasome-spliced peptides.

Titin-Related Familial Dilated Cardiomyopathy: Factors Associated With Disease Onset, Renee Johnson, Robert A Fletcher, Stacey Peters, Monique Ohanian, Magdalena Soka, Andrei Smolnikov, Katherine E Abihider, Michael J Ackerman, Flavie Ader, Mohammed M Akhtar, Ahmad S Amin, Euan A Ashley, John J Atherton, Rachel Austin, Annette F Baas, Richard D Bagnall, Samantha Barratt Ross, Jean-Louis Blouin, Emily E Brown, Henning Bundgaard, Douglas Cannie, Przemyslaw Chmielewski, Gemma Correnti, Maria Generosa Crespo-Leiro, Matteo Dal Ferro, Lisa M Dellefave-Castillo, Fernando Dominguez, Dennis Dooijes, Anne M Dybro, Youssef Ed Demri, Mohamed El Hachmi, Luis Escobar-Lopez, Sarah Jajesnica Foye, Maria Franaszczyk, Marta Gigli, Esther Gonzalez Lopez, Adeline Goudal, Sharon Graw, Michel Guipponi, Eric Haan, Jan Haas, Daniel J Hammersley, Frederikke G Hansen, Christopher S Hayward, Thomas Morris Hey, Stephane Heymans, Carolyn Y Ho, Arjan C Houweling, Jodie Ingles, Angela Ingrey, Andrew Jabbour, Paul A James, Joeri A Jansweijer, Jan D H Jongbloed, Anne M Keogh, Jose M Larrañaga-Moreira, Ronald H Lekanne Deprez, Ivan Macciocca, Peter S Macdonald, Nicolas Mansencal, Julia Mansour, Cristina Martinez-Veira, Barbara Mcdonough, Julie Mcgaughran, Kristen Medo, Marco Merlo, Ewa Michalak, Lorenzo Monserrat, Helen Mountain, Steven A Muller, Anne M Murphy, Brittney Murray, Emily C Oates, Elizabeth Ormondroyd, Nicholas Pachter, Alessia Paldino, Aurélien Palmyre, Naveen L Pereira, Kermshlise C Picard, Nicola Poplawski, Sanjay Prasad, Julie Proukhnitzky, Jean-Francois Pruny, Patricia Reant, Pascale Richard, Anne Ronan, Farbod Sedaghat-Hamedani, Christopher Semsarian, Garrett Storm, Sophie Stroeks, Petros Syrris, Matthew R G Taylor, Kate Thomson, Tina Thompson, J Peter Van Tintelen, Christoffer Rasmus Vissing, Kathryn E Waddell-Smith, Mathew Wallis, Dominica Zentner, Clare Arnott, Ali J Marian, Jaewon Oh, Siv Fokstuen, Cynthia A James, Roberto Barriales-Villa, Benjamin Meder, Karim Wahbi, John R Giudicessi, Victoria N Parikh, James S Ware, Nicolas Piriou, Caroline Rooryck, Neal K Lakdawala, Luisa Mestroni, Gianfranco Sinagra, Perry M Elliott, Hugh Watkins, Elizabeth M Mcnally, Philippe Charron, Karin Y Van Spaendonck-Zwarts, Pablo Garcia-Pavia, Maria Luisa Peña-Peña, Jens Mogensen, Alex Hoerby Christensen, Zofia T Bilińska, Torsten B Rasmussen, Jonathan G Seidman, Christine E Seidman, Anneline S J M Te Riele, Job A J Verdonschot, Yigal M Pinto, Imke Christiaans, Diane Fatkin

The Brown Foundation: Institute of Molecular Medicine

Background and aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv.

Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM.

Results: A total of 3158 subjects in 1043 …