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Small molecules, big data and something (often red blood cells) in between…
Angelo D’Alessandro

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Now out in Blood @ash.hematology.org @bloodjournals.hematology.org ashpublications.org/blood/articl... Really proud of this one, and grateful to the reviewers for the constructive criticism. It really is a much better paper now!
New study reveals POCA method for dual protein & lipid interactome mapping using a single singlet oxygen photosensitizer! PMID:41652064, Nat Chem Biol 2026, @nchembio https://doi.org/10.1038/s41589-026-02140-1 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪
10d
2mo
Angelo D’Alessandro
Key Points. Deep proteomics defines a complete, contamination-free RBC proteome (3,775 proteins) and O2-dependent interactome by Xlinking proteomicsThe Ban
ashpublications.org
The red blood cell proteome and interactome identify a Band 3-BLVRB axis regulating hypoxic metabolic adaptation
Shicheng Guo
Labor of love announcement: Red blood cells make up 83% of the cells in the human body. Mature RBCs lack nuclei (no gene expression) and organelles, and >90% of their dry weight is hemoglobin. Yet we have lacked a clean, contamination-free map of their proteome. Until now. doi.org/10.1101/2025...
6mo
The physical properties of cellular membranes are influenced by protein and lipid interactions. In situ proximity labeling interactomic methods are well suited to characterize these dynamic and often fleeting interactions. Yet, available methods require distinct chemistries for proteins and lipids. Here we establish a singlet oxygen-based photocatalytic proximity labeling platform (POCA) that reports intracellular interactomes for both proteins and lipids using cell-penetrant photosensitizer reagents. Cholesterol-directed POCA captured known and unprecedented cholesterol-binding proteins, including protein complexes sensitive to intracellular cholesterol levels and proteins uniquely captured by physiologically relevant lipoprotein uptake. Protein-directed POCA accurately mapped intracellular membrane complexes, defined sterol-dependent changes to the interactome of the cholesterol transport protein Aster-B and revealed singlet oxygen-mediated domain-specific Aster crosslinking. More br
doi.org
Photosensitizer proximity labeling captures the lipid and protein interactomes | Nature Chemical Biology
Deep Red Blood Cell Proteome Defines the Band 3 N-Terminus Interactome as a Regulator of Hypoxic Adaptation via BLVRB-Dependent S-Nitroso Transfer
Red blood cells (RBCs) have long been regarded as passive oxygen carriers, yet growing evidence reveals a complex, dynamic proteome independent of de novo gene expression. Here, we define the erythroc...
doi.org
Angelo D’Alessandro