Biology subjects

Person, A.

Publications and source records attributed to Person, A..

5 recordsLinked to original sources

bioRxiv2026

Acute degron-mediated RUNX1 loss reprograms enhancer activity to epigenetically drive epithelial destabilization and initiate cancer hallmarks

The RUNX1 transcription factor mediates cell-type specific gene expression. RUNX1 suppression and perturbations are recurrently associated with breast tumor initiation and progression. However, the mechanisms governing the dual roles of RUNX1 in sustaining the mammary epithelial phenotype while epigenetically suppressing initiation of cancer-compromised gene expression are poorly understood. To address this, we used the power of degron-mediated acute, selective, and complete RUNX1 ablation in human mammary epithelial cells. RUNX1 mediates promoter and distal enhancer-driven expression of a gene cohort. Dynamic epigenomic responsiveness upon RUNX1 ablation reveals a rapid and selective decrease in chromatin accessibility and H3K27ac at RUNX1-bound enhancers, but not promoters. While differentially initiated and expressed genes contacted by RUNX1-bound enhancers are enriched in pathways involved in epithelial maintenance and stemness, genes with RUNX1-promoter occupancy support DNA damage responsiveness. Modified cell morphology, metabolic control, increased breast cancer stemness, plasticity, anchorage-independent survival, chemoresistance, and perturbed DNA damage reactivity are observed upon RUNX1 ablation. Together, these findings define RUNX1 as an epigenetic tumor suppressor that maintains epithelial cell state by preserving enhancer activity and preventing gene expression associated with hallmarks of cancer.

cancer biology↗

bioRxiv2026

Functional cerebellar connectomes interfacing motor adaptation and reinforcement feedback

Motor adaptation is driven by sensory prediction errors, yet reinforcement feedback can alter the speed and retention of adaptive behaviors. The cerebellum is central in motor adaptation, but posterior lobules, especially Lobule VI (CB6) and Crus I (CBcrus1), also participate in reinforcement-related signaling. Serotoninergic and dopaminergic systems, key modulators of motivational processes, directly influence cerebellar activity. However, how these neuromodulatory systems contribute to cerebellar network organization and to reinforcement-based adaptation in humans remains unclear. We employed a multimodal framework (Receptor-Enriched Analysis of functional Connectivity by Targets; REACT) using PET-derived Serotonin/Dopamine Transporter (SERT/DAT) templates to enrich resting-state functional Magnetic Resonance Imaging (rs-fMRI). We estimated SERT- and DAT-enriched functional connectivity from CB6 and CBcrus1 within motor-adaptation and reinforcement-learning networks, and tested their correlations with performance in a visuomotor adaptation task completed under reward and punishment. Our findings show lobule-specific neuromodulatory organization within the cerebellum. CB6 exhibited predominantly DAT- and SERT-enriched connectivity with motor adaptation networks, while CBcrus1 showed stronger SERT-enriched communication extending to both motor and reinforcement networks. Crucially, distinct cerebello-cortical neuromodulatory networks predicted individual differences in adaptation rate. DAT-enriched CBcrus1 connectivity was linked to punishment-driven adaptation, whereas SERT-enriched cerebello-orbitofrontal connectivity predicted faster adaptation across both reward and punishment contingencies. Furthermore, we observed overlaps between SERT- and DAT-enriched networks in the medial orbitofrontal area for Crus I, which predicted retention following punishment, underscoring the role of convergent neuromodulation in stabilizing adapted movements. We conclude that partially segregated yet convergent cerebello-cortical networks support interactions between motor and motivational behaviors, with combined and opposing effects of serotonergic and dopaminergic neuromodulation accounting for the speed and retention of adaptive behaviors.

neuroscience↗

bioRxiv2023

Molecular blueprints of the Langya virus attachment and fusion glycoproteins

Langya virus (LayV) is a recently discovered henipavirus (HNV), isolated from febrile patients in China. HNV entry into host cells is mediated by the attachment (G) and fusion (F) glycoproteins which are the main targets of neutralizing antibodies. We show here that the LayV F and G glycoproteins promote membrane fusion with human, mouse and hamster target cells using a different, yet unknown, receptor than NiV and HeV and that NiV-and HeV-elicited monoclonal and polyclonal antibodies do not cross-react with LayV F and G. We determined cryo-electron microscopy structures of LayV F, in the prefusion and postfusion states, and of LayV G, revealing previously unknown conformational landscapes and their distinct antigenicity relative to NiV and HeV. We computationally designed stabilized LayV G constructs and demonstrate the generalizability of an HNV F prefusion-stabilization strategy. Our data will support the development of vaccines and therapeutics against LayV and closely related HNVs.

biochemistry↗

bioRxiv2023

Myomatrix arrays for high-definition muscle recording

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous systems actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ("Myomatrix arrays") that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a "motor unit", during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous systems motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and in identifying pathologies of the motor system.

neuroscience↗

bioRxiv2017

Imaging specific cellular glycan structures using glycosyltransferases via click chemistry

Heparan sulfate (HS) is a polysaccharide fundamentally important for biologically activities. T/Tn antigens are universal carbohydrate cancer markers. Here, we report the specific imaging of these carbohydrates using a mesenchymal stem cell line and human umbilical vein endothelial cells (HUVEC). The staining specificities were demonstrated by comparing imaging of different glycans and validated by either removal of target glycans, which results in loss of signal, or installation of target glycans, which results in gain of signal. As controls, representative key glycans including O-GlcNAc, lactosaminyl glycans and hyaluronan were also imaged. HS staining revealed novel architectural features of the extracellular matrix (ECM) of HUVEC cells. Results from T/Tn antigen staining suggest that O-GalNAcylation is a rate-limiting step for O-glycan synthesis. Overall, these highly specific approaches for HS and T/Tn antigen imaging should greatly facilitate the detection and functional characterization of these biologically important glycans.

molecular biology↗