Christopher S. Thom
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View article: IGF-1 from bone marrow Adipoq-lineage cells stimulates endocortical bone formation in mature female mice
IGF-1 from bone marrow Adipoq-lineage cells stimulates endocortical bone formation in mature female mice Open
Insulin-like growth factor 1 (IGF-1) is an anabolic signal promoting growth, differentiation and function of both embryonic and postnatal tissues. Both endocrine and paracrine functions of IGF-1 have been documented to regulate bone growth…
View article: Tropomyosin 1 promotes platelet adhesion and clot contraction to inhibit thrombosis
Tropomyosin 1 promotes platelet adhesion and clot contraction to inhibit thrombosis Open
Background: Failures in thrombosis prevention and treatment demand novel therapeutic approaches. We hypothesized that novel genetic determinants of thrombosis may be hiding in plain sight in human genetics data sets for relevant traits. Ge…
View article: Inflammation, anemia and Vitamin D status determine infant thrombocytosis risk
Inflammation, anemia and Vitamin D status determine infant thrombocytosis risk Open
Extreme thrombocytosis (EXT, >1000×10 3 platelets/μl blood) occurs in infants due to infection, inflammation, and/or anemia. EXT can present diagnostic dilemmas, sometimes prompting invasive testing and anticoagulation therapy. Our prior w…
View article: Genetically determined platelet traits impact stroke risk through multiple mechanisms and cell types
Genetically determined platelet traits impact stroke risk through multiple mechanisms and cell types Open
Stroke remains a leading cause of death and disability worldwide. Current antiplatelet and anticoagulant treatments are prone to failure. Heritable blood and platelet traits contribute to stroke risk, but related mechanisms are not fully u…
View article: Tropomyosin 1 promotes platelet adhesion and clot contraction separate from its roles in developmental hematopoiesis
Tropomyosin 1 promotes platelet adhesion and clot contraction separate from its roles in developmental hematopoiesis Open
Genome-wide associations studies (GWAS) have linked the Tropomyosin 1 ( Tpm1 ) gene locus to quantitative blood trait variation, but related mechanisms are unclear. Tpm1 encodes an actin-binding protein that stabilizes actin filaments and …
View article: Single-cell transcriptomics reveal individual and cooperative effects of trisomy 21 and GATA1s on hematopoiesis
Single-cell transcriptomics reveal individual and cooperative effects of trisomy 21 and GATA1s on hematopoiesis Open
Trisomy 21 (T21) is associated with baseline erythrocytosis, thrombocytopenia, neutrophilia, transient abnormal myelopoiesis (TAM), and myeloid leukemia of Down syndrome (ML-DS). TAM and ML-DS blasts harbor mutations in GATA1, resulting in…
View article: An improvement project standardizing low prophylactic platelet transfusion dosing for infants
An improvement project standardizing low prophylactic platelet transfusion dosing for infants Open
Background Platelet transfusions are frequently given to preterm infants to prevent bleeding, but randomized trials demonstrated harmful effects from current practices. Problem Many platelet transfusions were administered in 15–20 mL/kg do…
View article: The E3 ubiquitin ligase Cul5 regulates hematopoietic stem cell function for steady-state hematopoiesis in mice
The E3 ubiquitin ligase Cul5 regulates hematopoietic stem cell function for steady-state hematopoiesis in mice Open
The balance of hematopoietic stem cell (HSC) self-renewal versus differentiation is essential to ensure long-term repopulation capacity while allowing response to events that require increased hematopoietic output. Proliferation and differ…
View article: Multimodal analysis of <i>in vitro</i> hematopoiesis reveals blood cell-specific genetic impacts on complex disease traits
Multimodal analysis of <i>in vitro</i> hematopoiesis reveals blood cell-specific genetic impacts on complex disease traits Open
In vitro hematopoiesis systems can be used to define mechanisms for blood cell formation and function, produce cell therapeutics, and model blood cell contributions to systemic disease. Hematopoietic progenitor cell (HPC) production remain…
View article: Integrated Local and Systemic Communication Factors Regulate Nascent Hematopoietic Progenitor Escape During Developmental Hematopoiesis
Integrated Local and Systemic Communication Factors Regulate Nascent Hematopoietic Progenitor Escape During Developmental Hematopoiesis Open
Mammalian blood cells originate from specialized ‘hemogenic’ endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall…
View article: Tropomyosin 1 Has Separate Roles in Murine Platelet Function and Developmental Hematopoiesis
Tropomyosin 1 Has Separate Roles in Murine Platelet Function and Developmental Hematopoiesis Open
Background Genome-wide association studies (GWAS) have linked thousands of sites with platelet trait variation, but it can be difficult to define causal genes and mechanisms. Genetic polymorphisms that decrease Tropomyosin 1 (Tpm1) express…
View article: Integrated local and systemic communication factors regulate nascent hematopoietic progenitor escape during developmental hematopoiesis
Integrated local and systemic communication factors regulate nascent hematopoietic progenitor escape during developmental hematopoiesis Open
Mammalian blood cells originate from specialized hemogenic endothelial (HE) cells in major arteries. During the endothelial-to-hematopoietic transition (EHT), nascent hematopoietic stem cells (HSCs) bud from the arterial endothelial wall a…
View article: <scp>CDK8</scp> /19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes
<span>CDK8</span> /19 inhibition triggers a switch from mitosis to endomitosis in cord blood megakaryocytes Open
Summary Neonatal and adult megakaryocytes differ in proliferative capacity and ploidy levels, and neonatal and adult platelets differ in function, gene expression, and protein content. The mechanisms underlying these differences are incomp…
View article: Genetically influenced tobacco and alcohol use behaviors impact erythroid trait variation
Genetically influenced tobacco and alcohol use behaviors impact erythroid trait variation Open
Genome wide association studies (GWAS) have associated thousands of loci with quantitative human blood trait variation. Loci and related genes that impact blood trait variation may regulate blood cell-intrinsic biological processes, or alt…
View article: Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis
Tropomyosin 1 deficiency facilitates cell state transitions and enhances hemogenic endothelial cell specification during hematopoiesis Open
Tropomyosins coat actin filaments to impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 (TPM1) with human blood trait variation. TPM1 has been shown to regulate blood cell forma…
View article: Mendelian randomization analyses clarify the effects of height on cardiovascular diseases
Mendelian randomization analyses clarify the effects of height on cardiovascular diseases Open
An inverse correlation between stature and risk of coronary artery disease (CAD) has been observed in several epidemiologic studies, and recent Mendelian randomization (MR) experiments have suggested causal association. However, the extent…
View article: Consensus transfusion guidelines for a large neonatal intensive care network
Consensus transfusion guidelines for a large neonatal intensive care network Open
Neonates and infants hospitalized in the neonatal intensive care unit (NICU) frequently require blood product transfusions, but clinical practices vary widely. Many very low birth weight (VLBW) infants receive packed red blood cell (RBC) o…
View article: Single-cell transcriptomics reveal individual and synergistic effects of Trisomy 21 and GATA1s on hematopoiesis
Single-cell transcriptomics reveal individual and synergistic effects of Trisomy 21 and GATA1s on hematopoiesis Open
Trisomy 21 (T21), or Down syndrome (DS), is associated with baseline macrocytic erythrocytosis, thrombocytopenia, and neutrophilia, as well as transient abnormal myelopoiesis (TAM) and myeloid leukemia of DS (ML-DS). TAM and ML-DS blasts b…
View article: High rate of extreme thrombocytosis indicates bone marrow hyperactivity and splenic dysfunction among congenital diaphragmatic hernia patients
High rate of extreme thrombocytosis indicates bone marrow hyperactivity and splenic dysfunction among congenital diaphragmatic hernia patients Open
Pediatric extreme thrombocytosis (EXT, platelet count > 1000 x 103/µL) is rare. In a single center retrospective analysis of hospitalized children with EXT, infants with congenital diaphragmatic hernia (CDH) were overrepresented. In genera…
View article: Modeling primitive and definitive erythropoiesis with induced pluripotent stem cells
Modeling primitive and definitive erythropoiesis with induced pluripotent stem cells Open
During development, erythroid cells are produced through at least 2 distinct hematopoietic waves (primitive and definitive), generating erythroblasts with different functional characteristics. Human induced pluripotent stem cells (iPSCs) c…
View article: Single-Cell Transcriptomics Reveal Altered Hematopoietic Mechanisms Driven By T21 and GATA1s
Single-Cell Transcriptomics Reveal Altered Hematopoietic Mechanisms Driven By T21 and GATA1s Open
Introduction Trisomy 21 (T21) is associated with baseline erythrocytosis and thrombocytopenia and risk of transient abnormal myelopoiesis (TAM) and acute megakaryoblastic leukemia of Down syndrome (ML-DS). TAM and ML-DS are characterized b…
View article: Phosphoproteomics reveals content and signaling differences between neonatal and adult platelets
Phosphoproteomics reveals content and signaling differences between neonatal and adult platelets Open
Background and Objective Recent clinical studies have shown that transfusions of adult platelets increase morbidity and mortality in preterm infants. Neonatal platelets are hyporesponsive to agonist stimulation, and emerging evidence sugge…
View article: Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis
Tropomyosin 1 deficiency facilitates cell state transitions to enhance hemogenic endothelial cell specification during hematopoiesis Open
Tropomyosins coat actin filaments and impact actin-related signaling and cell morphogenesis. Genome-wide association studies have linked Tropomyosin 1 ( TPM1 ) with human blood trait variation. Prior work suggested that TPM1 regulated bloo…
View article: Consensus Blood Product Transfusion Guidelines for a Large Neonatal Care Network
Consensus Blood Product Transfusion Guidelines for a Large Neonatal Care Network Open
product transfusions, but clinical practices vary widely. Many very low birth weight (VLBW) infants receive packed red blood cell (RBC) or platelet transfusions during their initial NICU stay, with incidence inversely proportional to gesta…
View article: Generation of a human<i>Tropomyosin 1</i>knockout iPSC line
Generation of a human<i>Tropomyosin 1</i>knockout iPSC line Open
The CHOPWT17_TPM1KOc28 iPSC line was generated to interrogate the functions of Tropomyosin 1 ( TPM1 ) in primary human cell development. This line was reprogrammed from a previously published wild type control iPSC line.
View article: Genetically influenced tobacco and alcohol use behaviors impact erythroid trait variation
Genetically influenced tobacco and alcohol use behaviors impact erythroid trait variation Open
Genome wide association studies (GWAS) have associated thousands of loci with quantitative human blood trait variation. Blood trait associated loci and related genes may regulate blood cell-intrinsic biological processes, or alternatively …
View article: Supplementary Figures 1-3 from Oncogenesis Caused by Loss of the SNF5 Tumor Suppressor Is Dependent on Activity of BRG1, the ATPase of the SWI/SNF Chromatin Remodeling Complex
Supplementary Figures 1-3 from Oncogenesis Caused by Loss of the SNF5 Tumor Suppressor Is Dependent on Activity of BRG1, the ATPase of the SWI/SNF Chromatin Remodeling Complex Open
Supplementary Figures 1-3 from Oncogenesis Caused by Loss of the SNF5 Tumor Suppressor Is Dependent on Activity of BRG1, the ATPase of the SWI/SNF Chromatin Remodeling Complex