MPharmacol (hons); PhD
Senior Postdoctoral Research Fellow
Understanding the early changes that occur as monocytes differentiate to become macrophages or are exposed to different stimuli is key to understanding how the biology of these cells can be harnessed therapeutically.
Monocytes and macrophages are highly plastic cells of the innate immune system that can drive both inflammatory and anti-inflammatory processes in disease. Understanding the changes that occur as monocytes differentiate to become macrophages and as macrophages are exposed to different stimuli is key to understanding how the biology of these cells can be harnessed therapeutically.
My recent research has been in two main areas, monocyte recruitment to sites of vascular inflammation and the control of macrophage function by tetrahydrobiopterin.
I have established key methods to study monocyte recruitment in vascular inflammation. These include characterising a novel GFP reporter mouse, the hCD68GFP mouse, in both health and vascular disease models. Using cells from this mouse I perform adoptive transfer studies to look for the specific recruitment of the transferred monocytes and early changes that occur in these cells at sites of inflammation.
Tetrahydrobiopterin is an essential co-factor for nitric oxide synthase (NOS) enzymes that may have additional important functions.I have established in vitro systems to study primary macrophages that are deficient in tetrahydrobiopterin in the presence and absence of NOS expression. I identified a key role for tetrahydrobiopterin in macrophage biology and in the activation of the redox-regulated transcription factor NRF2. More recently, in collaboration with The Jenner Institute, I have shown that the loss of Gch1 in macrophages is protective in mycobacterial infection models.
I joined the University of Oxford from the Cancer Research UK London Research Institute where I completed my PhD in Immunology and a short follow-up post-doc position. Prior to this I obtained a Master of Pharmacology degree from the University of Bath, including a year in industry at GlaxoWellcome. In my career to date I have studied myeloid cell biology in a range of inflammatory and infectious models from inflammation-induced skin cancer to bacterial infection and atherosclerosis. My current research focuses on understanding the role of monocytes and macrophages in inflammation and disease.
Regulation of mycobacterial infection by macrophage Gch1 and tetrahydrobiopterin.
McNeill E. et al, (2018), Nat Commun, 9
Improved cellular uptake of perfluorocarbon nanoparticles for in vivo murine cardiac 19F MRS/MRI and temporal tracking of progenitor cells.
Constantinides C. et al, (2018), Nanomedicine
The metabolite BH4 controls T cell proliferation in autoimmunity and cancer.
Cronin SJF. et al, (2018), Nature, 563, 564 - 568
Roles for endothelial cell and macrophage Gch1 and tetrahydrobiopterin in atherosclerosis progression.
Douglas G. et al, (2018), Cardiovasc Res, 114, 1385 - 1399
Metabolic Regulation of Adipose Tissue Macrophage Function in Obesity and Diabetes.
Appari M. et al, (2018), Antioxid Redox Signal, 29, 297 - 312