Angelo D’Alessandro
@dalessandrolab.bsky.social
Small molecules, big data and something (often red blood cells) in between…
Pinned
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
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...
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...
Reposted by Angelo D’Alessandro
On the outside back cover of issue 1 of Lab on a Chip:
Surface acoustic wave hemolysis assay for evaluating stored red blood cells.
#OpenAccess from Angelo D'Alessandro, Xiaoyun Ding et al @dalessandrolab.bsky.social @cuanschutz.bsky.social @colorado.edu
Read now: pubs.rsc.org/en/content/a...
Surface acoustic wave hemolysis assay for evaluating stored red blood cells.
#OpenAccess from Angelo D'Alessandro, Xiaoyun Ding et al @dalessandrolab.bsky.social @cuanschutz.bsky.social @colorado.edu
Read now: pubs.rsc.org/en/content/a...
January 8, 2026 at 1:51 PM
On the outside back cover of issue 1 of Lab on a Chip:
Surface acoustic wave hemolysis assay for evaluating stored red blood cells.
#OpenAccess from Angelo D'Alessandro, Xiaoyun Ding et al @dalessandrolab.bsky.social @cuanschutz.bsky.social @colorado.edu
Read now: pubs.rsc.org/en/content/a...
Surface acoustic wave hemolysis assay for evaluating stored red blood cells.
#OpenAccess from Angelo D'Alessandro, Xiaoyun Ding et al @dalessandrolab.bsky.social @cuanschutz.bsky.social @colorado.edu
Read now: pubs.rsc.org/en/content/a...
Reposted by Angelo D’Alessandro
Cracking the code of blood: How genetics and metabolism are transforming transfusions
🔗 Read the full Transfusion Today article here: https://isbtweb.foleon.com/transfusion-today/transfusion-today-october-2025/cracking-the-code-of-blood
#TransfusionMedicine #ISBT #TransfusionToday
🔗 Read the full Transfusion Today article here: https://isbtweb.foleon.com/transfusion-today/transfusion-today-october-2025/cracking-the-code-of-blood
#TransfusionMedicine #ISBT #TransfusionToday
Cracking the Code of Blood - Transfusion Today - October 2025
isbtweb.foleon.com
December 19, 2025 at 10:00 AM
Cracking the code of blood: How genetics and metabolism are transforming transfusions
🔗 Read the full Transfusion Today article here: https://isbtweb.foleon.com/transfusion-today/transfusion-today-october-2025/cracking-the-code-of-blood
#TransfusionMedicine #ISBT #TransfusionToday
🔗 Read the full Transfusion Today article here: https://isbtweb.foleon.com/transfusion-today/transfusion-today-october-2025/cracking-the-code-of-blood
#TransfusionMedicine #ISBT #TransfusionToday
Reposted by Angelo D’Alessandro
Reposted by Angelo D’Alessandro
Terrific to have our paper, led by @tjflemin.bsky.social, featured as a plenary article in @bloodjournal.bsky.social today: ashpublications.org/blood/articl...
December 18, 2025 at 6:01 PM
Terrific to have our paper, led by @tjflemin.bsky.social, featured as a plenary article in @bloodjournal.bsky.social today: ashpublications.org/blood/articl...
Reposted by Angelo D’Alessandro
link.springer.com/article/10.1...
The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells
The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells
The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells - The EMBO Journal
Oxidative stress is a major driver of cardiovascular disease; however, the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characte...
link.springer.com
December 18, 2025 at 8:57 AM
link.springer.com/article/10.1...
The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells
The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells
Congrats to Sweta and to you, Eric!
December 10, 2025 at 3:57 PM
Congrats to Sweta and to you, Eric!
Reposted by Angelo D’Alessandro
As always, it takes a village... So grateful to the many collaborators that made this study happen, and to #NIH #NHLBI for the support
#hematology #RBC #RedBloodCell #Erythrocyte #Hypoxia #Exercise #Physiology @cuanschutz.bsky.social
#hematology #RBC #RedBloodCell #Erythrocyte #Hypoxia #Exercise #Physiology @cuanschutz.bsky.social
December 1, 2025 at 2:31 PM
As always, it takes a village... So grateful to the many collaborators that made this study happen, and to #NIH #NHLBI for the support
#hematology #RBC #RedBloodCell #Erythrocyte #Hypoxia #Exercise #Physiology @cuanschutz.bsky.social
#hematology #RBC #RedBloodCell #Erythrocyte #Hypoxia #Exercise #Physiology @cuanschutz.bsky.social
Similar mechanisms exists in plants: under hypoxia-like conditions (high CO₂/low O₂), NO levels rise and S-nitrosate GAPDH at C152, transiently modulating its activity and redirecting carbon flux like in RBCs! This parallel highlights a conserved NO-relay logic tuning metabolism across kingdoms
December 1, 2025 at 2:31 PM
Similar mechanisms exists in plants: under hypoxia-like conditions (high CO₂/low O₂), NO levels rise and S-nitrosate GAPDH at C152, transiently modulating its activity and redirecting carbon flux like in RBCs! This parallel highlights a conserved NO-relay logic tuning metabolism across kingdoms
Together, the data outline a Band 3–BLVRB–hemoglobin network that links oxygen sensing, redox chemistry, and metabolic adaptation in an anucleate cell.
December 1, 2025 at 2:31 PM
Together, the data outline a Band 3–BLVRB–hemoglobin network that links oxygen sensing, redox chemistry, and metabolic adaptation in an anucleate cell.
Mechanistically, BLVRB Cys109 functions as an NO-transfer relay, modulating glycolytic enzymes such as GAPDH through S-nitrosation. This provides a redox-based feedback mechanism that tunes metabolism to oxygen availability.
December 1, 2025 at 2:31 PM
Mechanistically, BLVRB Cys109 functions as an NO-transfer relay, modulating glycolytic enzymes such as GAPDH through S-nitrosation. This provides a redox-based feedback mechanism that tunes metabolism to oxygen availability.
Population-scale RBC proteome-QTL analyses (13,000 donors) show coordinated variation in SLC4A1 and BLVRB abundance, supporting the presence of a conserved regulatory axis across individuals.
December 1, 2025 at 2:31 PM
Population-scale RBC proteome-QTL analyses (13,000 donors) show coordinated variation in SLC4A1 and BLVRB abundance, supporting the presence of a conserved regulatory axis across individuals.
In humanized mice, loss of the Band 3 N-terminus disrupts glycolytic activation, lowers 2,3-BPG production, and impairs exercise tolerance, linking this molecular module to whole-organism physiology.
December 1, 2025 at 2:31 PM
In humanized mice, loss of the Band 3 N-terminus disrupts glycolytic activation, lowers 2,3-BPG production, and impairs exercise tolerance, linking this molecular module to whole-organism physiology.
A key finding is that BLVRB (biliverdin reductase B) binds the Band 3 N-terminus under oxygenated conditions and dissociates under hypoxia, when Band 3–deoxyhemoglobin interactions increase. This reversible switch integrates structural, redox, and metabolic control.
December 1, 2025 at 2:31 PM
A key finding is that BLVRB (biliverdin reductase B) binds the Band 3 N-terminus under oxygenated conditions and dissociates under hypoxia, when Band 3–deoxyhemoglobin interactions increase. This reversible switch integrates structural, redox, and metabolic control.
Despite the lack of de novo gene expression, the architecture of the human RBC proteome is oxygen responsive through ultra-structural changes. Using deep proteomics, cross-linking interactomics, structural biochemistry, and mouse models, we map how these changes are organized around Band 3 (SLC4A1).
December 1, 2025 at 2:31 PM
Despite the lack of de novo gene expression, the architecture of the human RBC proteome is oxygen responsive through ultra-structural changes. Using deep proteomics, cross-linking interactomics, structural biochemistry, and mouse models, we map how these changes are organized around Band 3 (SLC4A1).
By flow-sorting ultra-pure RBCs, we quantified 3,775 proteins—a high-confidence, contamination-free reference proteome. The full dataset is publicly available in the Deep Red portal:
🔗 angelo-dalessandro.github.io/deep-red-sup...
Yes, Deep Red is a wink to Dario Argento’s classic 1970s thriller!
🔗 angelo-dalessandro.github.io/deep-red-sup...
Yes, Deep Red is a wink to Dario Argento’s classic 1970s thriller!
Deep Red: Red Blood Cell Proteome 2025
angelo-dalessandro.github.io
December 1, 2025 at 2:31 PM
By flow-sorting ultra-pure RBCs, we quantified 3,775 proteins—a high-confidence, contamination-free reference proteome. The full dataset is publicly available in the Deep Red portal:
🔗 angelo-dalessandro.github.io/deep-red-sup...
Yes, Deep Red is a wink to Dario Argento’s classic 1970s thriller!
🔗 angelo-dalessandro.github.io/deep-red-sup...
Yes, Deep Red is a wink to Dario Argento’s classic 1970s thriller!
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...
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...
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
December 1, 2025 at 2:31 PM
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...
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...
Reposted by Angelo D’Alessandro
Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia: Cell www.cell.com/cell/fulltex...
Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia
Reduced levels of the essential metabolite heme are a common feature of acute myeloid
leukemia, and consequently, leukemic cells are highly sensitive to inhibition of de
novo heme synthesis. Blockade ...
www.cell.com
November 20, 2025 at 3:29 PM
Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia: Cell www.cell.com/cell/fulltex...
Kudos to the amazing work by @grkeele.bsky.social at RTI International, Gary Churchill @jacksonlab.bsky.social and Jim Zimring at Canadian Blood Services
November 19, 2025 at 8:25 PM
Kudos to the amazing work by @grkeele.bsky.social at RTI International, Gary Churchill @jacksonlab.bsky.social and Jim Zimring at Canadian Blood Services
STEAP3 variation also mapped to several apolipoproteins (including APOA1, APOC3, APOE), linking RBC iron handling to lipid oxidation and vesiculation pathways, potentially bridging neurodegenerative disease biology to RBC iron metabolism with systemic oxidative stress.
November 19, 2025 at 8:24 PM
STEAP3 variation also mapped to several apolipoproteins (including APOA1, APOC3, APOE), linking RBC iron handling to lipid oxidation and vesiculation pathways, potentially bridging neurodegenerative disease biology to RBC iron metabolism with systemic oxidative stress.
This work also represents, to our knowledge, the first pQTL + PTM-QTL map in an enucleated cell type, showing how genetic differences established during erythropoiesis continue to shape the mature RBC proteome through redox and degradative pathways.
November 19, 2025 at 8:24 PM
This work also represents, to our knowledge, the first pQTL + PTM-QTL map in an enucleated cell type, showing how genetic differences established during erythropoiesis continue to shape the mature RBC proteome through redox and degradative pathways.
A second locus, Steap3, influenced the oxidation of lipids and proteins, vesiculation-related proteins (including several apolipoproteins), and storage-related hemolysis.
Higher Steap3 activity correlated with greater oxidative stress and lower post-transfusion recovery.
Higher Steap3 activity correlated with greater oxidative stress and lower post-transfusion recovery.
November 19, 2025 at 8:24 PM
A second locus, Steap3, influenced the oxidation of lipids and proteins, vesiculation-related proteins (including several apolipoproteins), and storage-related hemolysis.
Higher Steap3 activity correlated with greater oxidative stress and lower post-transfusion recovery.
Higher Steap3 activity correlated with greater oxidative stress and lower post-transfusion recovery.
We used humanized mice expressing either canonical human HBB or a C93A variant.
Loss of βCys93 altered glutathione balance, increased oxidative modifications, changed proteolytic signatures, and reduced post-transfusion recovery.
These effects align with predictions from the genetic mapping.
Loss of βCys93 altered glutathione balance, increased oxidative modifications, changed proteolytic signatures, and reduced post-transfusion recovery.
These effects align with predictions from the genetic mapping.
November 19, 2025 at 8:24 PM
We used humanized mice expressing either canonical human HBB or a C93A variant.
Loss of βCys93 altered glutathione balance, increased oxidative modifications, changed proteolytic signatures, and reduced post-transfusion recovery.
These effects align with predictions from the genetic mapping.
Loss of βCys93 altered glutathione balance, increased oxidative modifications, changed proteolytic signatures, and reduced post-transfusion recovery.
These effects align with predictions from the genetic mapping.
The Hbb locus was particularly influential.
Certain founder strains carry an additional cysteine at β13, while others carry only the conserved β93 cysteine.
Variation at these positions was associated with widespread differences in oxidative PTMs and glutathione-related chemistry.
Certain founder strains carry an additional cysteine at β13, while others carry only the conserved β93 cysteine.
Variation at these positions was associated with widespread differences in oxidative PTMs and glutathione-related chemistry.
November 19, 2025 at 8:24 PM
The Hbb locus was particularly influential.
Certain founder strains carry an additional cysteine at β13, while others carry only the conserved β93 cysteine.
Variation at these positions was associated with widespread differences in oxidative PTMs and glutathione-related chemistry.
Certain founder strains carry an additional cysteine at β13, while others carry only the conserved β93 cysteine.
Variation at these positions was associated with widespread differences in oxidative PTMs and glutathione-related chemistry.
Four loci accounted for much of this trans-regulation:
• Hbb (β-globin)
• Hba (α-globin)
• Steap3 (ferrireductase involved in iron handling)
• Mon1a (vesicular trafficking / iron recycling)
• Hbb (β-globin)
• Hba (α-globin)
• Steap3 (ferrireductase involved in iron handling)
• Mon1a (vesicular trafficking / iron recycling)
November 19, 2025 at 8:24 PM
Four loci accounted for much of this trans-regulation:
• Hbb (β-globin)
• Hba (α-globin)
• Steap3 (ferrireductase involved in iron handling)
• Mon1a (vesicular trafficking / iron recycling)
• Hbb (β-globin)
• Hba (α-globin)
• Steap3 (ferrireductase involved in iron handling)
• Mon1a (vesicular trafficking / iron recycling)