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.
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 to atherosclerosis. My current research focuses on understanding the role of monocytes and macrophages in inflammation and disease.
Monocytes and macrophages are highly plastic cells of the innate immune system that can drive both inflammatory and anti-inflammatory processes in disease, depending on their activation state. 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 redox control of macrophage function by tetrahydrobiopterin.
I have established key methods to study monocyte recruitment in vascular inflammation. These include characterizing 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 recently identified a key role for tetrahydrobiopterin in macrophage redox state and in the activation of the redox-regulated transcription factor NRF2. I am currently studying the implications of this finding in disease models.
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
Endothelial Cell Tetrahydrobiopterin Modulates Sensitivity to Ang (Angiotensin) II-Induced Vascular Remodeling, Blood Pressure, and Abdominal Aortic Aneurysm.
Chuaiphichai S. et al, (2018), Hypertension, 72, 128 - 138
Deficiency in endothelial cell tetrahydrobiopterin increases resistance vascular remodelling, blood pressure, and susceptibility to aortic abdominal aneurysm in response to angiotensin II
Chuaiphichai S. et al, (2018), Cardiovascular research, 114, S90 - S90
Fast, quantitative, murine cardiac 19F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T.
Constantinides C. et al, (2018), Plos one, 13