I am an MRC Clinician Scientist and Honorary Consultant Physician at Imperial College Healthcare NHS Trust.
I am investigating the role of microglia in brain disease. Microglia are referred to as the “policemen of the brain” because they activate in response to almost any brain injury. This includes inflammatory disease like multiple sclerosis (MS) but also degenerative disease like Alzheimer’s and Parkinson’s (and many others too). The way in which microglia respond to these diseases is very important, because the microglial response partly determines how fast the disease progresses. My research involves studying the biology of microglia – particularly mitochondrial function - in order to find drugs to modulate their responses and therefore slow the progression of these diseases. I also use modern imaging techniques (positron emission tomography or PET) to detect and characterise microglia in the brains of living patients.
During my PhD (funded by the Wellcome Trust) I studied a microglial protein called TSPO. TSPO is used as a target for PET scanning to detect microglia in the brains of patients. With in vitro pharmacology, I discovered that the binding affinity of TSPO PET tracers is sensitive to a genetic mutation. This means that two patients with the same amount of TSPO will have different results from PET scans, if one patient carries the genetic mutation and the other does not. The genetic mutation is very common, and so unless the TSPO genetic code for each patient is known, the scans will give very misleading results. Because of this, all PET imaging centres now test the TSPO genetic code before scanning patients with TSPO PET tracers.
After my PhD, as a Clinical Lecturer (funded by the NIHR) I demonstrated this lab finding in vivo, with a first-in-man TSPO-PET blocking study. Based on this project I was presented with the 2013 Society of Nuclear Medicine Young Investigator Award (Neuroscience section, 1st place). With a starter grant from The Academy of Medical Sciences, I moved to Jack Antel’s neuroinflammation lab at McGill University in Canada where I began to explore the function of TSPO in microglia and produced pilot data to help get funding for my current project.
I am currently funded through an MRC Clinician Scientist Award, working with Kambiz Alavian to examine the role of TSPO in mitochondrial biology and therefore microglial activation.
I am also investigating the therapeutic potential of TSPO ligands in various neuroinflammatory and neurodegenerative diseases including multiple sclerosis (funded by an MRC Pathfinder grant with Paul Matthews), Parkinson’s Disease (funded by a Michael J Fox Foundation award with David Dexter) and epilepsy (funded by an Impetus award with Michael Johnson). I am also working on methods to better understand the TSPO PET signal with a grant from Abbvie, in collaboration with Lisa Wells (Imanova).
If you are interested in working on any of these projects, or wanting to start a new one in this field, please do get in touch.
Nicholas R, Brooks D, Owen D, 2019, In Response to Letter from Fregonara et al. 2019., Mol Imaging Biol
et al., 2019, A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis, Brain, Vol:142, ISSN:1460-2156, Pages:3440-3455
et al., 2019, Confirmation of specific binding of the 18 kDa translocator protein (TSPO) radioligand [18F]GE-180: a blocking study using XBD173 in multiple sclerosis normal appearing white and grey matter, Molecular Imaging and Biology, Vol:21, ISSN:1536-1632, Pages:935-944
et al., 2019, A bioinformatics approach to understand the regulation of TSPO gene expression in myeloid cells, 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS, SAGE PUBLICATIONS LTD, Pages:222-222, ISSN:1352-4585
et al., 2019, Exploring the mitochondrial TSPO protein as a possible immunometabolic modulatory target for treatment of multiple sclerosis, 35th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS) / 24th Annual Conference of Rehabilitation in MS, SAGE PUBLICATIONS LTD, Pages:515-515, ISSN:1352-4585