Mortimer Poncz
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View article: Platelet-activating antibodies to the chemokine, platelet factor 4, in cerebral malaria differ from those in heparin-induced thrombocytopenia and vaccine-induced thrombotic thrombocytopenia.
Platelet-activating antibodies to the chemokine, platelet factor 4, in cerebral malaria differ from those in heparin-induced thrombocytopenia and vaccine-induced thrombotic thrombocytopenia. Open
Background: Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, primarily affecting children, with a mortality rate near 20% and no targeted treatment. Recent studies have identified platelet-activating autoa…
View article: Murine hematopoietic progenitor cell lines with erythroid and megakaryocyte potential
Murine hematopoietic progenitor cell lines with erythroid and megakaryocyte potential Open
Red blood cells and platelets derive from bi-potential bone marrow megakaryocyte-erythroid progenitors, but their study is constrained by cell scarcity and limited experimental systems. Here we show that conditional expression of a virally…
View article: Endothelial cell activation enhances thromboinflammation in vaccine-induced immune thrombotic thrombocytopenia
Endothelial cell activation enhances thromboinflammation in vaccine-induced immune thrombotic thrombocytopenia Open
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but serious complication of the ChAdOx1 nCOV-19 vaccine. In Australia, the diagnosis of VITT required the detection of antibodies against platelet factor 4 (PF4) in plasma…
View article: Transcription factor RUNX1 regulates coagulation factor XIII-A (F13A1): decreased platelet-megakaryocyte F13A1 expression and clot contraction in RUNX1 haplodeficiency
Transcription factor RUNX1 regulates coagulation factor XIII-A (F13A1): decreased platelet-megakaryocyte F13A1 expression and clot contraction in RUNX1 haplodeficiency Open
RUNX1 regulates platelet-megakaryocyte F13A1 expression, which is decreased in RHD, reflecting regulation of a coagulation protein by a hematopoietic transcription factor. Platelet and megakaryocyte clot contraction is decreased in RHD, re…
View article: Transcription Factor RUNX1 Regulates Coagulation Factor XIII-A (<i>F13A1</i>): Decreased Platelet-Megakaryocyte<i>F13A1</i>Expression and Clot Contraction in<i>RUNX1</i>Haplodeficiency
Transcription Factor RUNX1 Regulates Coagulation Factor XIII-A (<i>F13A1</i>): Decreased Platelet-Megakaryocyte<i>F13A1</i>Expression and Clot Contraction in<i>RUNX1</i>Haplodeficiency Open
Background Germline RUNX1 haplodeficiency (RHD) is associated with thrombocytopenia, platelet dysfunction and predisposition to myeloid malignancies. Platelet expression profiling of a RHD patient showed decreased F13A1, encoding for the A…
View article: The PF4-Centric Immunothrombotic Disorders, HIT, Vitt and APS, Lead to Complement Activation Responsive to Complement-Blocking Therapeutics
The PF4-Centric Immunothrombotic Disorders, HIT, Vitt and APS, Lead to Complement Activation Responsive to Complement-Blocking Therapeutics Open
Background: Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia with thrombosis (VITT)are highly prothrombotic disorders mediated by platelet -activating anti-PF4 antibodies (Abs). Studies from our lab and ot…
View article: Anti-Phospholipid Syndrome (APS) Antibody (Ab)-Induced Thrombosis Can be Blocked By Platelet Factor 4 (PF4)-Directed Abs: A Novel Therapeutic Approach for APS?
Anti-Phospholipid Syndrome (APS) Antibody (Ab)-Induced Thrombosis Can be Blocked By Platelet Factor 4 (PF4)-Directed Abs: A Novel Therapeutic Approach for APS? Open
Background: APS is an autoimmune thromboinflammatory disease characterized by thrombocytopenia, thrombosis, and/or complications in pregnancy. APS occurs in association with one or more antiphospholipid (aPL) Abs/IgGs whose major target is…
View article: Platelet integrin αIIbβ3 plays a key role in venous thrombogenesis in a mouse model
Platelet integrin αIIbβ3 plays a key role in venous thrombogenesis in a mouse model Open
Venous thrombosis (VT) is a common vascular disease associated with reduced survival and a high recurrence rate. Previous studies have shown that the accumulation of platelets and neutrophils at sites of endothelial cell activation is a pr…
View article: Marginated neutrophils in the lungs effectively compete for nanoparticles targeted to the endothelium, serving as a part of the reticuloendothelial system
Marginated neutrophils in the lungs effectively compete for nanoparticles targeted to the endothelium, serving as a part of the reticuloendothelial system Open
Nanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has not achieved this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies t…
View article: Studies of infused megakaryocytes into mice support a “catch-and-release” model of pulmonary-centric thrombopoiesis
Studies of infused megakaryocytes into mice support a “catch-and-release” model of pulmonary-centric thrombopoiesis Open
Many aspects of thrombopoiesis, the release of platelets from megakaryocytes (Mks), remain under debate, including where this process occurs. Murine lung in situ -microscopy studies suggested that a significant fraction of circulating plat…
View article: Packaging of supplemented urokinase into alpha granules of in vitro–grown megakaryocytes for targeted nascent clot lysis
Packaging of supplemented urokinase into alpha granules of in vitro–grown megakaryocytes for targeted nascent clot lysis Open
Fibrinolytics delivered into the general circulation lack selectivity for nascent thrombi, reducing efficacy and increasing the risk of bleeding. Urokinase-type plasminogen activator (uPA) transgenically expressed within murine platelets p…
View article: G6b-B antibody-based cis-acting platelet receptor inhibitors (CAPRIs) as a new family of anti-thrombotic therapeutics
G6b-B antibody-based cis-acting platelet receptor inhibitors (CAPRIs) as a new family of anti-thrombotic therapeutics Open
Platelets are highly reactive fragments of megakaryocytes that play a fundamental role in thrombosis and hemostasis. Predictably, all conventional anti-platelet therapies elicit bleeding, raising the question whether the thrombotic activit…
View article: Packaging of supplemented urokinase into naked alpha-granules of<i>in vitro</i>-grown megakaryocytes for targeted therapeutic delivery
Packaging of supplemented urokinase into naked alpha-granules of<i>in vitro</i>-grown megakaryocytes for targeted therapeutic delivery Open
Our prior finding that uPA endogenously expressed and stored in the platelets of transgenic mice prevented thrombus formation without causing bleeding, prompted us to develop a potentially clinically relevant means of generating anti-throm…
View article: Platelet factor 4 limits neutrophil extracellular trap– and cell-free DNA–induced thrombogenicity and endothelial injury
Platelet factor 4 limits neutrophil extracellular trap– and cell-free DNA–induced thrombogenicity and endothelial injury Open
Plasma cell-free DNA (cfDNA), a marker of disease severity in sepsis, is a recognized driver of thromboinflammation and a potential therapeutic target. In sepsis, plasma cfDNA is mostly derived from neutrophil extracellular trap (NET) degr…
View article: A Novel Adenovirus (Adv)-Vaccinated Murine Model Simulates the Prothrombotic Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Clinical Disorder
A Novel Adenovirus (Adv)-Vaccinated Murine Model Simulates the Prothrombotic Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Clinical Disorder Open
Background: VITT has emerged as a rare (10 -5 to 10 -6 vaccinated individuals), but life-threatening side-effect of post-AdV-based COVID-19 vaccination, characterized by rapidly progressive catastrophic thrombosis, thrombocytopenia and hig…
View article: Altered Platelet-Megakaryocyte Endocytosis and Trafficking of Albumin and Fibrinogen in<i>RUNX1</i>Haplodeficiency
Altered Platelet-Megakaryocyte Endocytosis and Trafficking of Albumin and Fibrinogen in<i>RUNX1</i>Haplodeficiency Open
Platelet α-granules have numerous proteins, some synthesized by megakaryocytes (MK) and others not synthesized but incorporated by endocytosis, an incompletely understood process in platelets/MK. Germline RUNX1 haplodeficiency, referred to…
View article: PAI-1 Deficiency Drives Pulmonary Vascular Smooth Muscle Remodeling and Pulmonary Hypertension
PAI-1 Deficiency Drives Pulmonary Vascular Smooth Muscle Remodeling and Pulmonary Hypertension Open
Pulmonary arterial hypertension (PAH) is a progressive and potentially a rapidly fatal disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PA) leading to increased pulmonary vascular resistance and right h…
View article: Treatment of thrombocytopenia and thrombosis in HIT in mice using deglycosylated KKO: a novel therapeutic?
Treatment of thrombocytopenia and thrombosis in HIT in mice using deglycosylated KKO: a novel therapeutic? Open
Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia associated with a highly prothrombotic state due to the development of pathogenic antibodies that recognize human platelet factor 4 (hPF4) complexed with various p…
View article: SLFN14 ribosomopathy and platelet dysfunction
SLFN14 ribosomopathy and platelet dysfunction Open
TP53 mutations are highly prevalent in other subtypes of PEL, it should be noted that they have not been detected in patients with NFIA-ETO2 fusions.This raises potential questions about using the new transplantable model reported here for…
View article: Fc modification to transform a pathogenic antibody into a potential therapeutic for thromboinflammatory disease
Fc modification to transform a pathogenic antibody into a potential therapeutic for thromboinflammatory disease Open
KKO is a HIT (heparin-induced thrombocytopenia)-like mouse monoclonal antibody (moAb) that binds to platelet factor 4 (PF4) when complexed to polyanions like heparin and neutrophil extracellular traps (NETs). Human (h) PF4 protected NETs f…
View article: Figure S3 from S100A8/S100A9 Promote Progression of Multiple Myeloma via Expansion of Megakaryocytes
Figure S3 from S100A8/S100A9 Promote Progression of Multiple Myeloma via Expansion of Megakaryocytes Open
Effect of TPO and S100A9 on in vitro MK differentiation.