Biology subjects

Ward, R.

Publications and source records attributed to Ward, R..

16 recordsLinked to original sources

bioRxiv2026

Dual Pathways of Extracellular ATP Action in Cancer Cells: Purinergic Signaling Driven Senescence and Macropinocytic ATP Internalization

BackgroundOpportunistic nutrient uptake is a hallmark of cancer metabolism. Cancer cells upregulate macropinocytosis to acquire extracellular nutrients to support growth and stress adaptation. We previously showed that extracellular ATP (eATP) is internalized by macropinocytosis and promotes multiple cancer phenotypes. Here, we tested whether eATP uptake is prevalent across cancers and whether eATP also induces senescence through purinergic receptor (PR) signaling. MethodsIntracellular ATP (iATP) levels were measured following eATP exposure across multiple cancer cell lines. eATP internalization was visualized in vitro and in vivo using a non-hydrolyzable fluorescent ATP analog together with high-molecular-weight dextran as a macropinocytosis marker. Senescence was quantified using three SA-{beta}-galactosidase assays and flow cytometry. Pharmacologic inhibitors of macropinocytosis and purinergic receptors were used to define pathway dependence. Combination treatments with the glucose transporter inhibitor DRB18 and the senolytic navitoclax were evaluated for antiproliferative effects. ResultseATP produced dose- and time-dependent increases in iATP across diverse cancer cell types. Imaging demonstrated widespread macropinocytic internalization of ATP in vitro and in tumor xenografts. eATP induced senescence in NSCLC cells, confirmed by multiple {beta}-gal assays and flow cytometry. PR inhibition significantly reduced senescence, whereas macropinocytosis inhibition had minimal effect on senescence induction. ConclusionseATP acts through dual pathways in cancer cells: macropinocytic internalization that elevates iATP and PR signaling that drives senescence. Targeting metabolic uptake together with senolytic therapy may offer a novel anticancer strategy.

cancer biology↗

bioRxiv2026

DNA methylation signatures of mismatch repair-deficient colorectal cancer

BackgroundColorectal cancer (CRC) is a molecularly heterogeneous disease shaped by both genetic and epigenetic alterations. Approximately 15% of CRCs display widespread CpG island hypermethylation, known as the CpG Island Methylator Phenotype (CIMP). CIMP-high (CIMP-H) tumours frequently exhibit MLH1 promoter hypermethylation, leading to mismatch repair deficiency (MMRd) and microsatellite instability (MSI). However, DNA methylation patterns associated with MSI, independent of CIMP and MLH1 silencing, and the influence of clinical variables such as anatomical location and patient age on the CRC methylome remain poorly characterised. MethodsWe performed epigenome-wide DNA methylation profiling of 259 primary CRC tissue samples using the Illumina EPICv2 array, comparing differential methylation between MSI and microsatellite stable (MSS) CRC, adjusting for tumour purity, MLH1 promoter methylation, CIMP status, and anatomical location, to account for known confounders. We further evaluated the independent effects of anatomical location and patient age on global methylation patterns. ResultsEpigenome-wide differential methylation between MSS and MSI CRC was dominated by MLH1 promoter hypermethylation. After adjusting for MLH1 hypermethylation and CIMP status, we identified a distinct set of 656 CpG sites associated with MMRd independent of MLH1 silencing. These included hypermethylation at LRP6, GSK3{beta}, and CDK12, implicating altered WNT signalling and transcriptional regulation pathways. Comparison of MSI subgroups revealed the co-occurrence of MLH1 hypermethylation with promoter hypermethylation at TXNRD1. Anatomical location showed a strong independent effect on methylation patterns, while we observed only modest effects of patient age on the CRC methylome after adjustment for confounders. ConclusionsWe identified a distinct methylation profile distinguishing MSS and MSI CRC, including MLH1-independent markers of MMRd, as well as novel differentially methylated loci within MSI subgroups. We further showed that anatomical location has a strong independent impact on the CRC methylome. Together, these findings refine the molecular characterisation of CRC and highlight potential epigenetic markers that could inform patient stratification and precision oncology.

cancer biology↗

bioRxiv2026

Convergence on BRAF and MAPK Signaling in Glioma Development in a P53-ENU model

Pediatric high-grade gliomas (HGGs) are aggressive and lethal brain tumors that account for 15- 20% of all pediatric central nervous system (CNS) malignancies and remain largely incurable. These tumors, despite having mutational targets that activate MAPK signaling, are frequently resistant to targeted therapies in their malignant states, but often show responses when they are in lower grade form. These findings suggest a need to identify and intercept early tumorigenic events that arise in earlier tumor developmental stages. To investigate the molecular events in glioma progression, we developed and characterized a NestinCre/+;Trp53fl/fl mouse model combined with in utero exposure to the classic chemical mutagen N-ethyl-N-nitrosourea (ENU). This model mimics the context of genetic predisposition paired with an environmental genotoxic insult, and mice with loss of TRP53 in early neural precursors who are exposed to ENU at embryonic day 13.5 reproducibly develop HGGs postnatally that retain features of the human tumors. By sampling discrete lesions at premalignant, early, and late stages, we observed progressive increases in genetic complexity, stemness features, and immune signatures across tumor evolution. Notably, a recurrent Braf mutation emerged in a majority of early lesions and persisted in advanced tumors, consistent with the occurrence of BRAFV600E mutations in human gliomas that arise in children and undergo transition from lower grade to higher grade stages. Additional components of the RAS-RAF-MAPK signaling cascade, including Kras, Nras and Nf1 were found to be mutated at the late tumor stage, indicating convergent activation of this pathway in this model. Cell lines derived from early lesions responded to BRAF inhibitors, but cells from endpoint tumors were less responsive. Together, this model reveals aspects of the molecular and cellular evolution of glioma development in vivo, and identifies RAS-MAPK signaling as a critical molecular bottleneck selected for the ENU-induced mutations. This genetic-environmental model may be valuable to understanding key determinants of glioma initiation and progression, and for evaluating new therapies that limit MAPK signaling.

cancer biology↗

bioRxiv2026

Cloud-Connected Pluripotent Stem Cell Platform Enhances Scientific Identity in Underrepresented Students

Stem cell research offers unique opportunities for authentic scientific engagement, yet infrastructure requirements have confined participation to elite institutions, perpetuating workforce disparities. We developed an integrated framework combining engineered biology, cloud-connected microscopy, and validated psychometric assessment to make pluripotent stem cell (PSC) experimentation widely accessible. The framework comprises three components: a doxycycline-inducible NGN2 mouse embryonic stem cell line for rapid neuronal specification, low-cost cloud microscopy for remote observation, and the validated Stem Cell Research Identity Scale (SCRIS) for quantifying educational outcomes. Implementation across a Title I high school and urban community college demonstrated significant increases in scientific identity. Students using differentiating PSCs showed broader science identity development than those using neuroblastoma cells, particularly in competence, research readiness, and recognition. High school students showed enhanced research competence gains compared to community college students despite equivalent intervention duration. Demographic analyses revealed enhanced effectiveness for Hispanic and first-generation college students. This framework provides a scalable model for broadening participation in advanced biomedical research.

scientific communication and education↗

bioRxiv2025

Unraveling the diversity and functional potential of cyanosphere microbiomes assembled from terrestrial cyanobacteria

The cyanosphere consists of heterotrophic microorganisms residing within the exopolysaccharide sheath of cyanobacteria, acting as a crucial interface between the cyanobacteria and their surrounding environment. Understanding the interactions between cyanobacteria and their cyanospheres is essential for predicting the success of terrestrial cyanobacteria in providing ecosystem services in nutrient-poor environments. However, knowledge of the microbial diversity within the cyanosphere remains limited. In this study, we employed metagenomic sequencing to reconstruct 410 metagenome-assembled genomes (MAGs) from cyanosphere-associated microbes linked to 56 unialgal terrestrial cyanobacteria cultures, representing 12 distinct cyanobacteria orders. Our findings revealed that the composition of cyanosphere microbial communities was unique to each cyanobacterial host and was significantly shaped by environmental factors such as habitat, precipitation, and temperature from which the cultures were originally obtained. Notably, three microbial genera, Brevundimonas, Devosia, and Sphingopyxis, were present in over 30% of the cyanospheres, forming a core cyanosphere microbiome. Functional gene analysis showed a distinction between the cyanobacteria and their associated cyanospheres, with dissimilatory nitrate reduction being the dominant pathway in the cyanosphere, while nitrogen fixation was more common in the cyanobacteria. Three cyanospheres also contained nitrogen fixation genes of which two hosts were nitrogen fixation capable themselves. The cyanosphere harbored genes for polysaccharide lyases, indicating a possible link to the exopolysaccharides produced by the cyanobacteria. Given the observed variability in microbial community composition and function across different cyanobacterial hosts, future ecological assessments and restoration efforts involving cyanobacteria should not only focus on the cyanobacteria themselves but also consider their associated microbial communities. ImportanceOur study identifies members of a highly understudied, and potentially under-valued, microbial community -- the cyanosphere. We used a diversity of terrestrial cyanobacteria to understand how the cyanosphere composition and predicted functions were influenced by the host cyanobacterium and environmental factors using metagenomics. This is a new approach to study the cyanosphere and provides insights into the diversity of terrestrial microbial communities. Importantly, our results underscore the need to consider microbial consortia when assessing the ecological potential of cyanobacteria in terrestrial restoration.

ecology↗

bioRxiv2025

Extracellular vesicles from diverse fungal pathogens induce species-specific and endocytosis-dependent immunomodulation

Microbial pathogens generate extracellular vesicles (EVs) for intercellular communication and quorum sensing. Microbial EVs also induce inflammatory pathways within host innate immune cells. We previously demonstrated that EVs secreted by Candida albicans trigger type I interferon signaling in host cells specifically via the cGAS-STING innate immune signaling pathway. Here, we show that despite sharing similar properties of morphology and internal DNA content, the interactions between EVs and the innate immune system differ according to the parental fungal species. EVs secreted by C. albicans, Saccharomyces cerevisiae, Cryptococcus neoformans, and Aspergillus fumigatus are endocytosed at different rates by murine macrophages triggering varied cytokine responses, innate immune signaling, and subsequent immune cell recruitment. Notably, cell wall constituents that decorate C. neoformans and A. fumigatus EVs inhibit efficient internalization by macrophages and dampen innate immune activation. Our data uncover the transcriptional and functional consequences of the internalization of diverse fungal EVs by immune cells and reveal novel insights into the early innate immune response to distinct clinically significant fungal pathogens.

microbiology↗

bioRxiv2024

A novel pan class-I glucose transporter inhibitor DRB18 exhibits synergistic effects in vitro and in vivo with paclitaxel against human non-small cell lung cancer

PurposeCancer cells depend on glucose for biomass synthesis, cell proliferation, and drug resistance. Glucose transporter (GLUT) transcripts as well as proteins are upregulated in human lungs and other cancers and are negatively correlated with patient survival, particularly GLUT1 and GLUT3. Thus, inhibiting GLUT function has been an attractive anticancer strategy. We previously characterized WZB117 and DRB18, first- and second-generation pan-class I GLUT inhibitors, respectively. DRB18 strongly inhibits glucose transport mediated by GLUT1-4 in non-small lung cancer (NSCLC) A549 cells in vitro and in vivo. Here, we report DRB18 as a more stable and potent anticancer compound, compared to WZB117. MethodsImmunohistochemistry analysis was performed in Lung adenocarcinoma (LUAD) tissue array to investigate GLUT1 and GLUT3 protein expression between normal, lower and higher stage LUAD patients. Bioinformatics analysis was performed to examine additive effect of GLUT3 to GLUT1 mediated prognosis in LUAD. Glucose uptake and resazurin dye-based proliferation assays were used to determine glucose uptake inhibitory and cell proliferation inhibitory against panel of human cancer cell lines A549, Panc1 and Hela. DRB18 potency was tested against the presence of extracellular nutrients glucose, glutamine and ATP. Synergism between DRB18 and clinically approved anticancer drugs was tested against cancer cells. DRB18 and advanced NSCLC drug Paclitaxel were tested for synergy in vitro and in vivo. ResultsGLUT1/3 combination exhibited higher hazard ratio than either GLUT1 and GLUT3 alone in many cancer types including LUAD. DRB18 reduced glucose uptake in NSCLC A549, pancreatic Panc1, and cervical Hela cancer cells with varied but strong anticancer potencies in the presence or absence of extracellular nutrients such as ATP and glucose. Combined with different clinical and pre-clinical anticancer compounds such as V9302, CB839, Sutent, Brigatinib, DRB18 significantly increased death of A549 and Panc1 cells. Noteworthy, DRB18 exhibited strong anticancer synergy with paclitaxel, an approved chemo drug for NSCLC, drastically reducing cancer cell proliferation in vitro and growth of A549 tumors grafted on the flank of nude mice without significant side effects, compared to single drug treatments. ConclusionsCollectively, our results demonstrate anticancer efficacy of pan class-I GLUT inhibitor DRB18 in combination with paclitaxel, providing a potentially more efficacious therapeutic strategy for treating advanced NSCLC and other cancers.

cancer biology↗

bioRxiv2023

BiP/GRP78 is a pro-viral factor for diverse dsDNA viruses that promotes the survival and proliferation of cells upon KSHV infection

The Endoplasmic Reticulum (ER)-resident HSP70 chaperone BiP (HSPA5) plays a crucial role in maintaining and restoring protein folding homeostasis in the ER. BiPs function is often dysregulated in cancer and virus-infected cells, conferring pro-oncogenic and pro-viral advantages. We explored BiPs functions during infection by the Kaposis sarcoma-associated herpesvirus (KSHV), an oncogenic gamma-herpesvirus associated with cancers of immunocompromised patients. Our findings reveal that BiP protein levels are upregulated in infected epithelial cells during the lytic phase of KSHV infection. This upregulation occurs independently of the unfolded protein response (UPR), a major signaling pathway that regulates BiP availability. Genetic and pharmacological inhibition of BiP halts KSHV viral replication and reduces the proliferation and survival of KSHV-infected cells. Notably, inhibition of BiP limits the spread of other alpha- and beta-herpesviruses and poxviruses with minimal toxicity for normal cells. Our work suggests that BiP is a potential target for developing broad-spectrum antiviral therapies against double-stranded DNA viruses and a promising candidate for therapeutic intervention in KSHV-related malignancies.

microbiology↗

bioRxiv2023

Essential Gene Knockdowns Reveal Genetic Vulnerabilities and Antibiotic Sensitivities in Acinetobacter baumannii

The emergence of multidrug-resistant Gram-negative bacteria underscores the need to define genetic vulnerabilities that can be therapeutically exploited. The Gram-negative pathogen, Acinetobacter baumannii, is considered an urgent threat due to its propensity to evade antibiotic treatments. Essential cellular processes are the target of existing antibiotics and a likely source of new vulnerabilities. Although A. baumannii essential genes have been identified by transposon sequencing (Tn-seq), they have not been prioritized by sensitivity to knockdown or antibiotics. Here, we take a systems biology approach to comprehensively characterize A. baumannii essential genes using CRISPR interference (CRISPRi). We show that certain essential genes and pathways are acutely sensitive to knockdown, providing a set of vulnerable targets for future therapeutic investigation. Screening our CRISPRi library against last-resort antibiotics uncovered genes and pathways that modulate beta-lactam sensitivity, an unexpected link between NADH dehydrogenase activity and growth inhibition by polymyxins, and anticorrelated phenotypes that underpin synergy between polymyxins and rifamycins. Our study demonstrates the power of systematic genetic approaches to identify vulnerabilities in Gram-negative pathogens and uncovers antibiotic-essential gene interactions that better inform combination therapies. ImportanceAcinetobacter baumannii is a hospital-acquired pathogen that is resistant to many common antibiotic treatments. To combat resistant A. baumannii infections, we need to identify promising therapeutic targets and effective antibiotic combinations. In this study, we comprehensively characterize the genes and pathways that are critical for A. baumannii viability. We show that genes involved in aerobic metabolism are central to A. baumannii physiology and may represent appealing drug targets. We also find antibiotic-gene interactions that may impact the efficacy of carbapenems, rifamycins, and polymyxins, providing a new window into how these antibiotics function in mono- and combination therapies. Our studies offer a useful approach for characterizing interactions between drugs and essential genes in pathogens to inform future therapies.

systems biology↗

bioRxiv2023

Magnetically Controlled Cyclic Microscale Deformation of in vitro Cancer Invasion Models

Mechanical cues play an important role in the metastatic cascade of cancer. Three-dimensional (3D) tissue matrices with tunable stiffness have been extensively used as model systems of the tumor microenvironment for physiologically relevant studies. Tumor-associated cells actively deform these matrices, providing mechanical cues to other cancer cells residing in the tissue. Mimicking such dynamic deformation in the surrounding tumor matrix may help clarify the effect of local strain on cancer cell invasion. Remotely controlled microscale magnetic actuation of such 3D in vitro systems is a promising approach, offering a non-invasive means for in situ interrogation. Here, we investigate the influence of cyclic deformation on tumor spheroids embedded in matrices, continuously exerted for days by cell-sized anisotropic magnetic probes, referred to as {micro}Rods. Particle velocimetry analysis revealed the spatial extent of matrix deformation produced in response to a magnetic field, which was found to be on the order of 200 {micro}m, resembling strain fields reported to originate from contracting cells. Intracellular calcium influx was observed in response to cyclic actuation, as well as an influence on cancer cell invasion from 3D spheroids, as compared to unactuated controls. Localized actuation at one side of a tumor spheroid tended to result in anisotropic invasion toward the {micro}Rods causing the deformation. In summary, our approach offers a strategy to test and control the influence of non-invasive micromechanical cues on cancer cell invasion and metastasis.

bioengineering↗

bioRxiv2022

Cloud-controlled microscopy enables remote project-based biology education in Latinx communities in the United States and Latin America

Project-based learning (PBL) has long been recognized as an effective way to teach complex biology concepts. However, not all institutions have the resources to facilitate effective project-based coursework for students. We have developed a framework for facilitating PBL using remote-controlled internet-connected microscopes. Through this approach, one lab facility can host an experiment allowing simultaneous interaction by many students worldwide. Experiments on this platform can be run on long timescales and with materials that are typically unavailable to high school classrooms. This allows students to perform novel research projects rather than just repeat standard classroom experiments. To investigate the impact of this program, we designed and ran six user studies with students worldwide. All experiments were executed in Santa Cruz and San Francisco, California, with observations and decisions made remotely by the students using their personal computers and cellphones. In surveys gathered after the experiments conclusion, students reported increased excitement for science and a greater desire to pursue a career in STEM. This framework represents a novel, scalable, and effective PBL approach that has the potential to democratize biology and STEM education around the world.

scientific communication and education↗

bioRxiv2022

Pericyte Heterogeneity Identified by 3D Ultrastructural Analysis of the Microvessel Wall

ABSTRACT/SUMMARYUnequivocal pericyte identification remains a limitation in the field of vascular biology given the lack of unique molecular marker. Compounding this challenge are the recently described heterogeneities in pericyte morphology across microvascular networks. Here, we found further support on the ultrastructural level for classifying pericytes into sub-types - "thin-strand" (TSPs), mesh (MP), and ensheathing (EP) pericytes - based on their architecture in the mouse brain microcirculation. We also observed several instances of an additional cell type in the medial layer between endothelial cells and pericytes, specifically associated with EPs. A conserved characteristic across PC subtypes was extracellular matrix (ECM) encompassing the vascular unit and dispersed among neighboring cells. ECM thicknesses fell within a specific range depending on vessel location, and only thinned where cells were in closer proximity. Pericytes and endothelial cells formed "peg-and-socket" structures at these locations, providing another distinguishing feature across PC subtypes. Unique contact locations seemed to be present between medial and endothelial cells, as well as between vascular cells and the brain parenchyma. The ECM surrounding EPs exhibited another notable configuration in that thin extensions radiated out from the vessel wall into the surrounding parenchyma, suggesting mechanical and/or biochemical roles. Considering these data together, ultrastructural observations may provide an orthogonal perspective on pericyte heterogeneity and the presence of medial cells in cerebrovascular walls as well as assessing ECM coverage as a criterion for PC identification and exploring PC-associated ECM extensions that may have unique relevance in health and disease.

cell biology↗

bioRxiv2020

Non-photopic and photopic visual cycles differentially regulate immediate, early and late-phases of cone photoreceptor-mediated vision

Cone photoreceptors in the retina enable vision over a wide range of light intensities. However, the processes enabling cone vision in bright light (i.e. photopic vision) are not adequately understood. Chromophore regeneration of cone photopigments may require the retinal pigment epithelium (RPE) and/or retinal Muller glia. In the RPE, isomerization of all-trans-retinyl esters (atRE) to 11-cis-retinol (11cROL) is mediated by the retinoid isomerohydrolase Rpe65. An alternative retinoid isomerase, dihydroceramide desaturase-1 (DES1), is expressed in RPE and Muller cells. The retinol-isomerase activities of Rpe65 and Des1 are inhibited by emixustat and fenretinide, respectively. Here, we tested the effects of these visual cycle inhibitors on immediate, early and late phases of cone photopic vision. In zebrafish larvae raised under cyclic light conditions, fenretinide impaired late cone photopic vision, whereas emixustat-treated zebrafish unexpectedly had normal vision. In contrast, emixustat-treated larvae raised under extensive dark-adaption displayed significantly attenuated immediate photopic vision concomitantly with significantly reduced 11-cis-retinaldehyde (11cRAL). Following 30 minutes of light, early photopic vision recovered, despite 11cRAL levels remaining significantly reduced. Defects in immediate cone photopic vision were rescued in emixustat- or fenretinide-treated larvae following exogenous 9-cis-retinaldehyde (9cRAL) supplementation. Genetic knockout of degs1 or retinaldehyde-binding protein 1b (rlbp1b) revealed that neither are required for photopic vision in zebrafish. Our findings define the molecular and temporal requirements of the non-photopic and photopic visual cycles for mediating vision in bright light.

biochemistry↗

bioRxiv2019

broad controls leg imaginal disc morphogenesis in Drosophila via regulation of cell shape changes and remodeling of extracellular matrix

Imaginal disc morphogenesis during metamorphosis in Drosophila melanogaster provides an excellent model to uncover molecular mechanisms by which hormonal signals effect physical changes during development. The broad (br) Z2 isoform encodes a transcription factor required for disc morphogenesis in response to 20-hydroxyecdysone, yet how it accomplishes this remains largely unknown. Here, we show that amorphic br5 mutant discs fail to remodel their basal extracellular matrix (ECM) after puparium formation and do not undergo necessary cell shape changes. RNA sequencing of wild type and mutant leg discs identified 717 genes differentially regulated by br; functional studies reveal that several are required for adult leg formation, particularly those involved in remodeling the ECM. Additionally, br Z2 expression is abruptly shut down at the onset of metamorphosis, and expressing it beyond this time results in failure of leg development during the late prepupal and pupal stages. Taken together, our results suggest that br Z2 is required to drive ECM remodeling, change cell shape, and maintain metabolic activity through the mid prepupal stage, but must be switched off to allow expression of pupation genes. Summary StatementThe Drosophila melanogaster ecdysone-responding transcription factor broad controls morphogenetic processes in leg imaginal discs during metamorphosis through regulation of genes involved in extracellular matrix remodeling, metabolism, and cell shape changes and rearrangements.

developmental biology↗

bioRxiv2018

Pharmacological Restoration of Visual Function in a Zebrafish Model of von-Hippel Lindau Disease

Von Hippel-Lindau (VHL) syndrome is rare, autosomal dominant disorder, characterized by hypervascularised tumour formation in multiple organ systems. Vision loss associated with retinal capillary hemangioblastomas remains one of the earliest complications of VHL disease. The mortality of Vhl-/- mice in utero restricted modelling of VHL disease in this mammalian model. Zebrafish harbouring a recessive germline mutation in the vhl gene represent a viable, alterative vertebrate model to investigate associated ocular loss-of-function phenotypes. Previous studies reported neovascularization of the brain, eye and trunk together with odema in the vhl-/- zebrafish eye. In this study, we demonstrate vhl-/- zebrafish almost entirely lack visual function. Furthermore, hyaloid vasculature networks in the vhl-/- eye are improperly formed and this phenotype is concomitant with development of an ectopic intraretinal vasculature. Sunitinib, a multi tyrosine kinase inhibitor, market authorised for cancer, reversed the ocular behavioural and morphological phenotypes observed in vhl-/- zebrafish. We conclude that the zebrafish vhl gene contributes to the endogenous molecular barrier that prevents development of intraretinal vasculature and that sunitinib can improve visual function and hyaloid vessel patterning while reducing abnormally formed ectopic intraretinal and choroidal vessels in vhl-/- zebrafish.

pharmacology and toxicology↗

bioRxiv2018

fMRI repetition suppression reveals no sensitivity to trait judgments from faces along the ventral visual stream or in the theory-of-mind network

The human face cues a wealth of social information, but the neural mechanisms that underpin social attributions from faces are not well known. In the current fMRI experiment, we used repetition suppression to test the hypothesis that populations of neurons in face perception and theory-of-mind neural networks would show sensitivity to faces that cue distinct trait judgments. Although faces were accurately discriminated based on associated traits, our results showed no evidence that face or theory-of-mind networks showed repetition suppression for face traits. Thus, we do not provide evidence for population coding models of face perception that include sensitivity to high and low trait features. Due to aspects of the experimental design, which bolstered statistical power and sensitivity, we have reasonable confidence that we could detect effects of a moderate size, should they exist. The null findings reported here, therefore, add value to models of neural organisation in social perception by showing instances where effects are absent or small. To test the generalisability of our findings, future work should test different types of trait judgment and different types of facial stimuli, in order to further probe the neurobiological bases of impression formation based on facial appearance.

neuroscience↗