Xunde Wang
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View article: Mitapivat improves red blood cell integrity by reducing membrane ubiquitination accumulation
Mitapivat improves red blood cell integrity by reducing membrane ubiquitination accumulation Open
Background: The ubiquitin-proteasome system (UPS)is essential for maintaining red blood cell (RBC) membrane homeostasis by degrading damaged and misfolded proteins, thus preventing the accumulation of potentially harmful protein aggregates…
View article: Cryo-electron tomography of sickled red blood cells towards a high-resolution in situ structure of HbS polymers and red cell cytoskeleton
Cryo-electron tomography of sickled red blood cells towards a high-resolution in situ structure of HbS polymers and red cell cytoskeleton Open
Sickle Cell Disease (SCD) is an inherited red cell disorder caused by the presence of the abnormal hemoglobin S (HbS) resulting from a single base substitution in the beta hemoglobin gene. SCD affects approximately 8 million people globall…
View article: The Amyloidogenic Transthyretin V122I Variant Increase Severity of Cardiac Phenotype and Mortality in Sickle Cell Disease
The Amyloidogenic Transthyretin V122I Variant Increase Severity of Cardiac Phenotype and Mortality in Sickle Cell Disease Open
The amyloidogenic V122I variant (valine to isoleucine substitution at position 122) of the transthyretin (TTR) gene is carried almost exclusively in people of African descent, about 3% African-Americans carry the variant. In the general po…
View article: Duffy Status and Hydroxyurea Dosing in Adult Patients with Sickle Cell Disease: A Potential for Iatrogenic Harm?
Duffy Status and Hydroxyurea Dosing in Adult Patients with Sickle Cell Disease: A Potential for Iatrogenic Harm? Open
Introduction: A lower absolute neutrophil count (ANC) is associated with the variant rs2814778 (c.1-67T>C) in the promotor of the ACKR1 gene. Homozygosity for rs2814778 results in the Duffy null phenotype. Duffy null patients have norma…
View article: Activating pyruvate kinase improves red blood cell integrity by reducing band 3 tyrosine phosphorylation
Activating pyruvate kinase improves red blood cell integrity by reducing band 3 tyrosine phosphorylation Open
In a phase 1 study (NCT04000165), we established proof of concept for activating pyruvate kinase (PK) in sickle cell disease (SCD) as a viable antisickling therapy. AG-348 (mitapivat), a PK activator, increased adenosine triphosphate (ATP)…
View article: In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation
In vivo measurement of RBC survival in patients with sickle cell disease before or after hematopoietic stem cell transplantation Open
Stable, mixed-donor–recipient chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) for patients with sickle cell disease (SCD) is sufficient for phenotypic disease reversal, and results from differences in donor/recipi…
View article: Random forest classifiers trained on simulated data enable accurate short read-based genotyping of structural variants in the alpha globin region at Chr16p13.3
Random forest classifiers trained on simulated data enable accurate short read-based genotyping of structural variants in the alpha globin region at Chr16p13.3 Open
In regions where reads don’t align well to a reference, it is generally difficult to characterize structural variation using short read sequencing. Here, we utilize machine learning classifiers and short sequence reads to genotype structur…
View article: Sickle cell allele <scp><i>HBB</i></scp>‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa
Sickle cell allele <span><i>HBB</i></span>‐rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa Open
Burkitt lymphoma (BL) is an aggressive B‐cell lymphoma that significantly contributes to childhood cancer burden in sub‐Saharan Africa. Plasmodium falciparum , which causes malaria, is geographically associated with BL, but the evidence re…
View article: Exploring Mitochondrial DNA Heteroplasmy in a Mouse Model of Sickle Cell Disease
Exploring Mitochondrial DNA Heteroplasmy in a Mouse Model of Sickle Cell Disease Open
BACKGROUND: Mitochondria are important in the pathology of sickle cell disease (SCD). They are abnormally retained in sickle red blood cells (RBCs) and the likely source of cell-free mitochondrial DNA (mtDNA), an erythrocytic-DAMP that tri…
View article: Genetic variants of <i>PKLR</i> are associated with acute pain in sickle cell disease
Genetic variants of <i>PKLR</i> are associated with acute pain in sickle cell disease Open
Acute pain, the most prominent complication of sickle cell disease (SCD), results from vaso-occlusion triggered by sickling of deoxygenated red blood cells (RBCs). Concentration of 2,3-diphosphoglycerate (2,3-DPG) in RBCs promotes deoxygen…
View article: Whole genome sequence-based haplotypes reveal a single origin of the 1393 bp <i>HBB</i> deletion
Whole genome sequence-based haplotypes reveal a single origin of the 1393 bp <i>HBB</i> deletion Open
Background Mutations of HBB give rise to two prevalent haemoglobin disorders—sickle cell disease (SCD) and β-thalassaemia. While SCD is caused by a single base substitution, nearly 300 mutations that downregulate expression of HBB have bee…
View article: The platelet NLRP3 inflammasome is upregulated in sickle cell disease via HMGB1/TLR4 and Bruton tyrosine kinase
The platelet NLRP3 inflammasome is upregulated in sickle cell disease via HMGB1/TLR4 and Bruton tyrosine kinase Open
A key inflammatory mechanism recently identified in platelets involves the Nod-like receptor nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK), which control activation of caspase-1…
View article: Analgesia by deletion of spinal neurokinin 1 receptor expressing neurons using a bioengineered substance P-<i>Pseudomonas</i> exotoxin conjugate
Analgesia by deletion of spinal neurokinin 1 receptor expressing neurons using a bioengineered substance P-<i>Pseudomonas</i> exotoxin conjugate Open
Cell deletion approaches to pain directed at either the primary nociceptive afferents or second-order neurons are highly effective analgesic manipulations. Second-order spinal neurons expressing the neurokinin 1 (NK1) receptor are required…
View article: Beta thalassaemia intermedia due to co‐inheritance of three unique alpha globin cluster duplications characterised by next generation sequencing analysis
Beta thalassaemia intermedia due to co‐inheritance of three unique alpha globin cluster duplications characterised by next generation sequencing analysis Open
Co-inheritance of α thalassaemia reduces chain imbalance and disease severity in β thalassaemia homozygotes, while increasing α globin output in heterozygotes increases chain imbalance, converting a typically asymptomatic carrier state to …