Denisa Wagner | |
---|---|
Born | Prague, Czechoslovakia |
Alma mater | |
Awards |
|
Scientific career | |
Thesis | (1980) |
Doctoral advisor | Richard O. Hynes |
Denisa D. Wagner is an American scientist currently the Edwin Cohn Professor of Pediatrics at Boston Children's Hospital (BCH), Harvard Medical School. [1] [2] [3] Wagner first arrived in the United States in 1975 as a refugee from Czechoslovakia. [4] She received her PhD in Biology from the Massachusetts Institute of Technology and taught at the University of Rochester and Tufts University before joining the Harvard faculty in 1994. [3] The Wagner Lab contributes in the fields of vascular biology, inflammation, and thrombosis. Her Lab focuses on how blood cells and endothelial cells respond to vascular injury. [1] Also her lab has been studying NETs (Neutrophil Extracellular Traps) for more than a decade. [5] In 2015, research from the lab shed light on healing wounds in patients with diabetes. [6] In the same year she received the Robert P. Grant Medal, which is the highest award of the International Society on Thrombosis and Hemostasis (ISTH).
Wagner is an Elected Fellow of the American Association for the Advancement of Science. [7] In 2017 the American Heart Association honored her as one of the year's Distinguished Scientists [8] and in 2021, she delivered the Russell Ross Memorial Lectureship in Vascular Biology. [9] In 2021, Wagner received the prestigious Henry B. Stratton Medal in Basic Science from the American Society of Hematology. [10] Dr. Wagner is widely published, [11] with more than 50,000 citations [12] and an h-index of 129.
A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes), and platelets (thrombocytes). Together, these three kinds of blood cells add up to a total 45% of the blood tissue by volume, with the remaining 55% of the volume composed of plasma, the liquid component of blood.
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. When severe, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems, depending on which arteries are affected.
Neutrophils are a type of white blood cell. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in different animals.
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue.
Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enlarged veins in the affected area, but some DVTs have no symptoms. The most common life-threatening concern with DVT is the potential for a clot to embolize, travel as an embolus through the right side of the heart, and become lodged in a pulmonary artery that supplies blood to the lungs. This is called a pulmonary embolism (PE). DVT and PE comprise the cardiovascular disease of venous thromboembolism (VTE). About two-thirds of VTE manifests as DVT only, with one-third manifesting as PE with or without DVT. The most frequent long-term DVT complication is post-thrombotic syndrome, which can cause pain, swelling, a sensation of heaviness, itching, and in severe cases, ulcers. Recurrent VTE occurs in about 30% of those in the ten years following an initial VTE.
Myeloperoxidase deficiency is a disorder featuring lack in either the quantity or the function of myeloperoxidase–an iron-containing protein expressed primarily in neutrophil granules. There are two types of myeloperoxidase deficiency: primary/inherited and secondary/acquired. Lack of functional myeloperoxidase leads to less efficient killing of intracellular pathogens, particularly Candida albicans, as well as less efficient production and release of neutrophil extracellular traps (NETs) from the neutrophils to trap and kill extracellular pathogens. Despite these characteristics, more than 95% of individuals with myeloperoxidase deficiency experience no symptoms in their lifetime. For those who do experience symptoms, the most common symptom is frequent infections by Candida albicans. Individuals with myeloperoxidase deficiency also experience higher rates of chronic inflammatory conditions. Myeloperoxidase deficiency is diagnosed using flow cytometry or cytochemical stains. There is no treatment for myeloperoxidase deficiency itself. Rather, in the rare cases that individuals experience symptoms, these infections should be treated.
NADPH oxidase is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white blood cells to engulf microorganisms. Human isoforms of the catalytic component of the complex include NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2.
Tissue factor, also called platelet tissue factor, factor III, or CD142, is a protein encoded by the F3 gene, present in subendothelial tissue and leukocytes. Its role in the clotting process is the initiation of thrombin formation from the zymogen prothrombin. Thromboplastin defines the cascade that leads to the activation of factor X—the tissue factor pathway. In doing so, it has replaced the previously named extrinsic pathway in order to eliminate ambiguity.
Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the PECAM1 gene found on chromosome17q23.3. PECAM-1 plays a key role in removing aged neutrophils from the body.
Intussusceptive angiogenesis also known as splitting angiogenesis, is a type of angiogenesis, the process whereby a new blood vessel is created. By intussusception a new blood vessel is created by splitting of an existing blood vessel in two. Intussusception occurs in normal development as well as in pathologic conditions involving wound healing, tissue regeneration, inflammation as colitis or myocarditis, lung fibrosis, and tumors amongst others.
Mean platelet volume (MPV) is a machine-calculated measurement of the average size of platelets found in blood and is typically included in blood tests as part of the CBC. Since the average platelet size is larger when the body is producing increased numbers of platelets, the MPV test results can be used to make inferences about platelet production in bone marrow or platelet destruction problems.
Neutrophil elastase is a serine proteinase in the same family as chymotrypsin and has broad substrate specificity. Neutrophil elastase is secreted by neutrophils during inflammation, and destroys bacteria and host tissue. It also localizes to neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.
Neutrophil extracellular traps (NETs) are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind pathogens. Neutrophils are the immune system's first line of defense against infection and have conventionally been thought to kill invading pathogens through two strategies: engulfment of microbes and secretion of anti-microbials. In 2004, a novel third function was identified: formation of NETs. NETs allow neutrophils to kill extracellular pathogens while minimizing damage to the host cells. Upon in vitro activation with the pharmacological agent phorbol myristate acetate (PMA), Interleukin 8 (IL-8) or lipopolysaccharide (LPS), neutrophils release granule proteins and chromatin to form an extracellular fibril matrix known as NET through an active process.
G protein-coupled receptor 32, also known as GPR32 or the RvD1 receptor, is a human receptor (biochemistry) belonging to the rhodopsin-like subfamily of G protein-coupled receptors.
Allograft inflammatory factor 1 (AIF-1) also known as ionized calcium-binding adapter molecule 1 (IBA1) is a protein that in humans is encoded by the AIF1 gene.
Endothelial activation is a proinflammatory and procoagulant state of the endothelial cells lining the lumen of blood vessels. It is most characterized by an increase in interactions with white blood cells (leukocytes), and it is associated with the early states of atherosclerosis and sepsis, among others. It is also implicated in the formation of deep vein thrombosis. As a result of activation, enthothelium releases Weibel–Palade bodies.
MFAP4 is an extracellular matrix protein encoded by the MFAP4 gene. It is part of the MFAP family of proteoglycans, which are involved in cell adhesion, intercellular interactions and the assembly and/or maintenance of elastic fibres.
Arturo Zychlinsky is a biologist and since 2001 director at the Max Planck Institute for Infection Biology. His research focuses on Neutrophil Extracellular Traps (NETs) which he discovered together with Volker Brinkmann, and the immune function of chromatin.
Owen McCarty is an American biomedical engineer who studies the dynamics of the vascular system in the context of cancer