Usua Oyarbide

Cleveland Clinic · Department of Cancer Biology

Shwachman-Diamond syndrome (SDS) is characterized by skeletal abnormalities, pancreatic insufficiency, and neutropenia, with an increased risk of developing myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Nearly all cases of SDS are caused by biallelic mutations in the SBDS gene, which is critical for ribosome assembly. SBDS inter...

Neutrophils are the shortest‐lived blood cells, which requires a prodigious degree of proliferation and differentiation to sustain physiologically sufficient numbers and be poised to respond quickly to infectious emergencies. More than 10 ⁷ neutrophils are produced every minute in an adult bone marrow—a process that is tightly regulated by a small...

Introduction. Shwachman-Diamond syndrome (SDS) is an inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities. Patients with SDS are predisposed to develop myeloid malignancy. Almost all individuals with SDS harbor biallelic mutations in SBDS. The partner of SBDS is EFL1, a r...

Introduction:Mutations in Stromal antigen 2 ( STAG2) are frequently found in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In mice, loss of Stag2 is embryonic lethal. Conditional knockout of Stag2 in adult mice results in MDS-like hematopoietic anomalies. Zebrafish harbor two paralogues of STAG2 ( stag2a and stag2b). To date, a c...

Defects in ribosomal biogenesis profoundly affect organismal development and cellular function, and these ribosomopathies produce a variety of phenotypes. One ribosomopathy, Shwachman–Diamond syndrome (SDS) is characterized by neutropenia, pancreatic exocrine insufficiency, and skeletal anomalies. SDS results from biallelic mutations in SBDS , whic...

Commercial fisheries have increased in all the world’s oceans with diverse unintended impacts on marine ecosystems. As a result of resource overlap, interactions between cetaceans and fisheries are a common occurrence and, in many cases, can give rise to significant conservation issues. Research on the distribution and types of such interactions is...

Shwachman-Diamond syndrome is a rare inherited bone marrow failure syndrome characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities. In 10-30%, transformation to a myeloid neoplasm occurs. Approximately 90% of patients have biallelic pathogenic variants in the SBDS gene located on human chromosome 7q11. In the pa...

Shwachman-Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoi-etic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman-Bodian-Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome ma...

Heperan sulfate proteoglycans (HSPGs) are constituents of the cell surface and extracellular matrix and are vital for various activities within the cell. The N-deacetylase/N-sulfotransferase (heparin glucosaminyl) family of enzymes, or NDST, modifies heparan sulfate (HS) by catalyzing both the N-deacetylation and the N-sulfation of N-acetylglucosam...

Ewing sarcoma (ES) is one of the most common and lethal pediatric cancers with a 5-year survival rate of less than 30% for those with metastatic disease. Approximately 25% of ES patients have metastatic disease at time of diagnosis. Current treatment for ES rests on an intensive regimen of five chemotherapeutic agents with a high level of toxicity....

Interactions between various cetacean species and fisheries are geographically widespread and diverse. Foraging in association with fishing activities may increase prey encounter rates and possibly increase the quantity and the quality of the food consumed. This paper describes interactions between benthic trawlers, targeting mainly Greenland halib...

Shwachman-Diamond syndrome (SDS) is characterized by exocrine pancreatic insufficiency, neutropenia, and skeletal abnormalities. Biallelic mutations in SBDS, which encodes a ribosome maturation factor, are found in 90% of SDS cases. Sbds-/- mice are embryonic lethal. Using CRISPR/Cas9 editing, we created sbds-deficient zebrafish strains. Sbds prote...

Background. Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency, skeletal defects, neutropenia, and an increased risk of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). SDS occurs in 1/75,000 births, and biallelic mutations in the SBDS gene account for ~90% of patients. The SBDS...

Inherited bone marrow failure syndromes are experiments of nature characterized by impaired hematopoiesis with cancer and leukemia predisposition. The mutations associated with inherited bone marrow failure syndromes affect fundamental cellular pathways, such as DNA repair, telomere maintenance, or proteostasis. How these disturbed pathways fail to...

In this issue of Blood, Bellanné-Chantelot et al noted that mutations in signal recognition particle 54 (SRP54) cause an inherited neutropenia in 23 individuals with features of both severe congenital neutropenia (SCN) and Shwachman-Diamond syndrome (SDS).

Neutrophils are the most common type of leukocyte in human circulating blood and constitute one of the chief mediators for innate immunity. Defined as a reduction from a normal distribution of values, neutropenia results from a number of congenital and acquired conditions. Neutropenia may be insignificant, temporary, or associated with a chronic co...

Pathologic variants in TP53 are known risk factors for the development of cancer. We report a 17-year-old male who presented with two primary sarcomas. Germline sequencing revealed a novel TP53 c.672 G>A mutation. Sequencing revealed wild-type TP53 in the parents, and there was no history of cancer in first-degree relatives. This de novo synonymous...

Introduction: Shwachman-Diamond Syndrome (SDS) is a complex disorder resulting in short stature, neutropenia, bony dysplasia, and pancreatic malabsorption. Individuals with SDS are also at increased risk for developing myelodysplastic syndrome and/or acute myeloid leukemia (AML). Its estimated incidence of 1 in 77,000 births makes SDS difficult to...

Usua Oyarbide, PhD1,2*, Margaret J Kell3*, Javier Farinas, BS1*, Rachel Hartig4*, Jacek Topczewski, PhD3* and Seth J. Corey, MD, MPH5,6 1Pediatrics, Northwestern University, Chicago, IL 2Pediatrics, VCU Massey Cancer Center, Richmond, VA 3Program in Developmental Biology, Pediatrics, Northwestern University Feinberg School of Medicine, Stanley Man...

Shwachman-Diamond syndrome (SDS) is a multisystem disorder characterized by neutropenia, exocrine pancreatic insufficiency, and skeletal abnormalities. Individuals with SDS are also at increased risk for developing myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). SDS results from mutations in the SBDS gene, which encodes a protei...

Abstract We evaluated the use of the gnotobiotic zebrafish system to study the effects of bacterial infection, and analyzed expression of genes involved in zebrafish innate immunity. Using a GFP-labeled strain of Vibrio anguillarum, we fluorescently monitored colonization of the zebrafish intestinal tract and used gene expression analysis to compar...

During the last few years zebrafish (Danio rerio) has revealed as a promising vertebrate model to elucidate the molecular basis of immunity (Traver et al. 2003; Yoder, 2009). As a matter of fact, this model has been used to study the host immune response under a number of microbial infections (Clatworthy et al. 2009; O'Toole et al. 2004; Rojo et al...

birds, possessing many of the cells and molecules found in higher verte-brates. However, unlike mammals, birds and fish red blood cells (RBCs) are nucleated and contain organelles in their cytoplasm. Nevertheless, the knowledge on the potential contribution of fish nucleated erythrocytes to the orchestration of the immune response after DNA vaccina...

The present study was carried out to examine the use of zebrafish (Danio rerio) as a preliminary screening model for testing the effect of potential immunostimulant substances on the innate immune system. β-Glucan, a polysaccharide used widely as an immunostimulant, was used as a representative molecule and tested on zebrafish embryos and larvae. T...