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Gorelik, M.

Publications and source records attributed to Gorelik, M..

2 recordsLinked to original sources

Stuck on you! Social brain stimulation increases the cognitive effort required to return to the egocentric perspective

Flexible switching between self and other perspectives is critical for adaptive social cognition and is thought to rely on the dynamic regulation of self-other representations. Although neuroimaging implicates the dorsomedial prefrontal cortex (dmPFC) and right temporoparietal junction (rTPJ) in perspective-taking, causal evidence for their specific contributions to perspective switching is lacking. Here, we applied focal transcranial direct current stimulation (f-tDCS) to the dmPFC and rTPJ while participants completed a visual perspective-taking task requiring switches between egocentric and altercentric viewpoints. Anodal stimulation to either site selectively increased the cognitive cost of switching back to the egocentric-perspective, without affecting switches into the altercentric-perspective. Rather than facilitating re-engagement with self-referential processing, stimulation enhanced altercentric persistence or impaired disengagement from the altercentric perspective. These findings provide novel causal evidence that both the dmPFC and rTPJ are involved in regulating the inhibition and updating of self-other representations during perspective switching. Results suggest that stimulation of these hubs may disrupt efficient realignment to the self, highlighting their role in maintaining an altercentric cognitive state. Future studies are required to uncover the precise neural computations that account for the comparable behavioural outcomes observed across distinct social brain hubs.

neuroscience↗

Structural surfaceomics reveals an AML-specific conformation of Integrin-β2 as a CAR-T therapy target

Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here, we explore the hypothesis that tumor cells express cancer-specific surface protein conformations, invisible to standard target discovery pipelines evaluating gene or protein expression, that can be identified and immunotherapeutically targeted. We term this strategy, integrating cross-linking mass spectrometry (XL-MS) with glycoprotein surface capture, "structural surfaceomics". As a proof of principle, we apply this technology to acute myeloid leukemia, a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin-{beta}2 as a structurally-defined, widely-expressed, AML-specific target. We develop and characterize recombinant antibodies to this protein conformation, and show that chimeric antigen receptor (CAR) T-cells eliminate AML cells and patient-derived xenografts without notable toxicity versus normal hematopoietic cells. Our findings validate an AML conformation-specific target antigen while demonstrating a toolkit for applying these strategies more broadly.

cancer biology↗