The Haematopoiesis and Leukocyte Biology laboratory focuses on understating the pathways contributing to enhanced leukocyte production and altered function in the context of (but not limited to) cardiovascular and metabolic diseases.
In Western societies, the consumption of diets high in calories, saturated fat, and cholesterol combined with a sedentary lifestyle lead to a high prevalence of atherosclerotic cardiovascular disease (CVD). High-circulating blood lipids, including elevated low-density lipoproteins (LDL) and triglyceride-rich lipoproteins, result in increased entry and retention of these particles in the arterial wall, leading to a macrophage-dominated chronic inflammatory process and eventuating in atherosclerotic plaque rupture or erosion, myocardial infarction, or thrombotic stroke. While elevated plasma cholesterol levels have an essential role in atherogenesis, comorbidities such as smoking, hypertension, and diabetes accelerate atherosclerotic CVD. In addition, chronic kidney disease, recurrent infections, myeloproliferative neoplasms, and autoimmune disease such as rheumatoid arthritis and systemic lupus erythematous also greatly increase the risk of athero- thrombosis. A common theme linking these diseases to athero- thrombosis is an overactive immune system, mediated in part by increased production and activation of innate immune cells. Our group seeks to understand these changes in the immune system from the level of the long-lived haematopoietic stem cells through to the mature effector cells such as monocytes and macrophages.
More specifically we study fundamental biological process contributing to the retention and liberation of haematopoietic stem cells (HSCs) within specific bone marrow (BM) niches and how these HSCs and the BM niche become altered in disease. We are interested in how these HSCs traffic to the spleen and initiate extramedullary haematopoiesis. In particular we have a focus on how inflammatory diseases associated with increased cardiovascular risk influence these pathways, including diabetes, obesity and autoimmune diseases such as rheumatoid arthritis. We also explore how these diseases influence the function of circulating cells, namely monocytes, neutrophils and platelets. We also have a strong interest in the role of plaque macrophages and pathways contributing to foam cell formation.
We are also exploring the two main outcomes of vascular disease, myocardial infarction and stroke and how these diseases influence the haematopoietic system to promote enhanced myelopoiesis, which is associated with a worse outcome.
We are also focused on exploring the utility or current treatments and developing novel therapies to target the pathways we have identified in our preclinical models that are also detect in patients with these diseases.
Video: Professor Andrew Murphy presenting at Future Medicine 2016, Germany (2min, 36sec)
- Fundamental process regulating haematopoiesis.
- Understand multi-organ communication to stimulate haematopoiesis.
- Determining how the body responds to hyperglycaemic spikes.
- Exploring if and how inflammatory diseases that are associated with increased cardiovascular risk impair the regression of atherosclerotic lesions.
- Understanding how enhanced reticulated platelets influence accelerated atherosclerosis in diabetes.
- Exploring the role of human monocyte subsets in cardiovascular disease.
- Investigating pathways contributing to foam cell formation in the atherosclerotic lesion.