Biology subjects

Rosenbalm, K. E.

Publications and source records attributed to Rosenbalm, K. E..

2 recordsLinked to original sources

bioRxiv2025

Glycan-Mediated Mechanosensing Regulates Megakaryocyte-Biased Hematopoietic Stem Cell Subsets.

Definitive hematopoietic stem and progenitor cells (HSPCs) development relies on intrinsic and extrinsic programs to meet homeostatic and stress-related demands. The comprehensive mechanisms governing HSPCs fate remain poorly understood. Our study identifies B4GALT1, a glycosyltransferase essential for N-glycosylation, as a key modulator of HSPC lineage decisions. We demonstrate that B4GALT1 deficiency disrupts glycosylation patterns within the bone marrow (BM) niche, resulting in oncogenic glycan signatures and altered expression of Mucin13 in HSPCs. Loss of B4GALT1 expands HSPC pools and promotes megakaryocyte priming in HSPCs through transcriptional and chromatin modifications, enhancing the Wnt-Mucin13 axis. Mucin13, an oncogene characterized by aberrant glycosylation, underscores the critical role of B4GALT1 in sustaining BM glycosylation and mechanosensing, thereby regulating HSPC fate through functional, transcriptional, and chromatin dynamics. These observations provide insights into the impact of glycan structures on HSPC function, lineage reprogramming, and malignant transformation.

cell biology↗

bioRxiv2020

Virus-Receptor Interactions of Glycosylated SARS-CoV-2 Spike and Human ACE2 Receptor

The current COVID-19 pandemic is caused by the SARS-CoV-2 betacoronavirus, which utilizes its highly glycosylated trimeric Spike protein to bind to the cell surface receptor ACE2 glycoprotein and facilitate host cell entry. We utilized glycomics-informed glycoproteomics to characterize site-specific microheterogeneity of glycosylation for a recombinant trimer Spike mimetic immunogen and for a soluble version of human ACE2. We combined this information with bioinformatic analyses of natural variants and with existing 3D-structures of both glycoproteins to generate molecular dynamics simulations of each glycoprotein alone and interacting with one another. Our results highlight roles for glycans in sterically masking polypeptide epitopes and directly modulating Spike-ACE2 interactions. Furthermore, our results illustrate the impact of viral evolution and divergence on Spike glycosylation, as well as the influence of natural variants on ACE2 receptor glycosylation that, taken together, can facilitate immunogen design to achieve antibody neutralization and inform therapeutic strategies to inhibit viral infection.

biochemistry↗