Sathiji Nageshwaran (2013 - 2016)

Friedrich’s ataxia (FRDA) is a progressive neurodegenerative disease affecting motor coordination from early childhood. During my TMT fellowship I have been able to undertake both benchside and clinical research relating to FRDA. At the bedside, patients were enrolled and completed a non-interventional longitudinal study to aide in the development of neurotechnology tools (in collaboration with Aldo Faisal, Department of Bioengineering, ICL) that can more precisely record change in disease status over time. The hope is that such tools may be used in clinical trials to hasten the therapeutic validation process. At the benchside I have developed a keen interest in transcriptional regulation and have investigated the effect of a number of chromatin modifiers on the expression of frataxin, the dysfunctional gene in FRDA. Building on this strong understanding of epigenetic gene regulation I have been able to secure a fellowship from the Friedrich’s Ataxia Research Alliance (FARA) to fund a project using Epigenetic Engineering as an investigative and possible therapeutic approach to FRDA. This work will be conducted within the Church Lab (Department of Genetics, Harvard Medical School).

Working within the program has also afforded me the opportunity to complete a book project (Drugs in Neurology, Oxford University Press) aiming to educate fellow clinicians on the pharmacotherapeutic options available in modern Neurology and their underlying mechanisms of action and evidence base.

Gregory Scott (2012 – 2016)

Traumatic brain injury (TBI) is the commonest cause of death and disability in the under-40s. Cognitive problems such as impairments of attention and memory are a major cause of this disability. Recently, abnormal levels of activated microglia have been demonstrated in the thalamus and striatum up to seventeen years after TBI. A prolonged and poorly regulated inflammatory response in TBI may be damaging, and treating persistent inflammation might be beneficial for cognitive function and long-term outcomes. The aims of my research are to validate the use of novel positron emission tomography (PET) ligands in inflammatory imaging of TBI, to characterise the relationship between brain inflammation and white matter damage, and to investigate the action of the tetracycline derivative minocycline on brain inflammation, structure and function.

Tim Dawes (2012 - 2015)

Right heart dysfunction is common in critical care and predicts poor outcome, though has no specific treatments. I am an intensive care and anaesthetics registrar interested in how right ventricular function is affected by anthropometrics, haemodynamics and genetics. During my PhD, I worked with Dr. Declan O’Regan, Professor Martin Wilkins and Professor Stuart Cook to develop three-dimensional, high-resolution models of the heart based on standard-acquisition MRI images. These models allow smaller effects, and effects limited to small areas of the heart, to be appreciated. By using this model, the influence of genetic variation and haemodynamics on the heart can be more accurately understood. I am delighted to be continuing this work into an Imperial College Clinical Lecturer post and ultimately hope to use this approach to identify signalling pathways amenable to intervention with the prospect of treatment for an important clinical problem.

Jaime Vera (2011-2015)

Microglial activation has been suggested as the main pathogenic mechanism responsible for the development of neurocognitive impairment in HIV-positive individuals on antiretroviral therapy. Identifying microglial activation in the brains of HIV individuals with neurocognitive impairment has been challenging so far, but Positron emission tomography (PET) using novel radioligands has the potential to identify microglial inflammation in this setting. My PhD is aimed at describing the pathogenesis of neurocognitive impairment in HIV-positive individuals on treatment using a combination of imaging and in vitro techniques. I hope my work will facilitate the development of new therapies targeting specific brain inflammatory pathways associated with HIV.
(The above overview was written whilst undertaking the programme).

Thomas Hopkins (2011-2015)

My research interest is ovarian cancer, a disease responsible for over 4,300 deaths in the UK every year. The leading cause of mortality is the development of resistance to standard chemotherapy (platinum-based agents). At present, there is no way to determine when patients have become resistant to platinum chemotherapy (termed platinum-resistant disease). Moreover, when resistance does develop, there are limited treatment options. My project focuses on a protein, LARP1, that appears to make ovarian cancer cells more aggressive and resistant to chemotherapy. In my project, I am using models of ovarian cancer to demonstrate for the first time that LARP1 is important in promoting tumour spread and makes tumours resistant to chemotherapy. I am also using patient samples to investigate LARP1 as a marker of disease progression. This project aims to define a new treatment target and disease marker for patients with platinum-resistant ovarian cancer, which could dramatically change how treatment decisions are made in the future.
(The above overview was written whilst undertaking the programme).

Alexander Comninos (2011- 2014)

During my clinical training in endocrinology, I developed a strong interest in reproductive endocrinology. I collected pilot data and successfully applied for this PhD Fellowship to investigate the novel reproductive hormones kisspeptin and neurokinin B. Kisspeptin is a crucial activator of reproduction and I showed that kisspeptin modulates downstream reproductive hormonal pulses, menstrual cycles, egg maturation (in IVF), as well as sexual and emotional brain processing in humans. I addition, I showed that Neurokinin B is a key trigger of menopausal hot flushes without significant effects of reproductive hormones. Collectively, my work has improved our understanding of reproductive physiology with translational relevance to the treatment of reproductive, psychosexual and menopausal disorders. I have published several papers and presented my work at international conferences with the award of several prizes including the prestigious ‘American Endocrine Society Award for Best Oral Presentation in Reproduction’. On completion of this Fellowship, I was awarded an NIHR Clinical Lectureship. Currently, I am heavily involved in clinical work and have recently been appointed as a Consultant Endocrinologist at Imperial. I continue to work on several research projects (funded by NIHR, MRC and BRC) with the aim of translating my findings for the benefit of my patients. My continued research and clinical contributions were recently recognised by the UK Society for Endocrinology with the award of the ‘Early Career Prize’ for the top young endocrinologist in the UK.

Ramzi Khamis (2010-2014)

As a cardiology SpR and Interventional Fellow, I developed an interest in identifying vulnerable atherosclerotic plaque. Joining this programme has given me the opportunity to work with Professors Dorian Haskard and Paul Matthews on the development of a multimodality, antibody-targeted, imaging strategy for the identification of vulnerable plaque. During my research period, my understanding of the role of the immune system in atherosclerosis was nourished by a rich collegiate atmosphere within the group. I am also working with Professor Haskard on biomarker development using anti oxidised LDL antibodies, and looking into the mechanisms by which antibodies against oxidised LDL manifest their protective or pathological effects.
(The above overview was written whilst undertaking the programme).

Evangelos Russo (2010- 2014)

I joined this programme following two years of registrar training in Gastroenterology at North West Thames. I am currently in the second year of my PhD Fellowship, investigating the potential use of TSPO and IL-2 radioligands to quantify inflammation in Crohn’s Disease. My aim is to be able to identify sub-clinical inflammation and quantify the inflammatory component of structuring lesions. This could allow us to use more aggressive anti-inflammatory treatment where necessary and could potentially prevent unwarranted operations.
(The above overview was written whilst undertaking the programme).

Nicola Kalk (2010 – 2013)

Alcohol dependence affects 1.1 million people in the United Kingdom. Although it is well-known that alcohol damages the liver, it is less recognised that alcohol damages the brain as well. Alcohol is estimated to contribute to 24% of cases of dementia. Even apparently healthy alcoholics have cognitive deficits, particularly in frontal lobe domains, and evidence of cerebral atrophy on brain imaging. The cause of this remains unclear, though thiamine deficiency has been emphasised. The role of inflammation – both peripheral inflammation and so-called neuroinflammation – in cognitive impairment as a result of acute and chronic neural insults has risen to prominence. Evidence from post-mortem studies and the pre-clincial literature suggests that heavy alcohol intake results in cytokine release in both the periphery and the brain. In addition, there is activation of microglia, resident macrophages, in the brain. There is some evidence that this worsens during withdrawal. I am currently running a study investigating the relationship between peripheral cytokine levels and cognition during alcohol detoxification. I am also hoping to use novel PET tracers which target microglial activation to establish whether there is microglial activation in the brains of recently abstinent alcoholics relative to healthy controls, and how this relates to cognitive function. It is my hope that this may provide a novel therapeutic target for the prevention of cognitive decline in this vulnerable population. 
(The above overview was written whilst undertaking the programme).

Alessandro Colasanti (2010 – 2013)

I have completed a specialist training in Psychiatry. My current research interest lies in neuropsychopharmacology and PET imaging. My first imaging project was aimed to characterise a practical and robust method to probe the endogenous opioid system in the living human brain. We used Positron Emission Tomography and the radiotracer [11C]carfentanil to demonstrate that the administration of amphetamine in healthy volunteers induced brain release of endogenous opioids. The current project aims to investigate the neuroinflammatory process in Multiple Sclerosis by imaging the activation of microglia, the sensors of brain pathology, using a novel TSPO PET radiotracer. This imaging technique may potentially contribute to characterise in-vivo the involvement of the brain cortex in the pathology of Multiple Sclerosis and its relationship to neuropsychiatric symptoms.
(The above overview was written whilst undertaking the programme).

Akila De Silva (2009- 2013)

Having completed 3 years of SpR training in Diabetes and Endocrinology, I was awarded a Translational Medicine Training Fellowship and am now in my final year of the programme. Based in the Section of Investigative Medicine on the Hammersmith Campus, I am part of the research group headed by Professor Stephen Bloom and Professor Waljit Dhillo. My main research interest lies in studying the neuroendocrinology of appetite control, and in particular, the interaction between anorectic peptide hormones (normally secreted postprandially by the gut) and CNS appetite centres in mediating the satiety response in humans. During my PhD project, using functional magnetic resonance imaging (fMRI), I demonstrated that the pattern of brain activation following intravenous infusion of the gut hormones PYY3-36 and GLP-17-36 amide to healthy, normal weight, fasted human subjects was similar to when the same subjects ate a meal and were infused with saline. PYY3-36 and GLP-17-36 infusion to fasted subjects also produced a reduction in subsequent food intake that was similar to the effect of feeding itself in reducing consumption at the next meal. These findings have consolidated our understanding of the normal physiology of human appetite control. The findings may be taken forward with a view to developing PYY and GLP-1 based treatments for obesity.
(The above overview was written whilst undertaking the programme).

David Owen (2007-2010)

During my PhD, I investigated the use of PET ligands to quantify the TSPO, a protein expressed in large numbers within macrophages and microglia. By quantifying the TSPO, and hence quantifying macrophage or microglial density, we can track the progression of various inflammatory diseases and monitor a response to treatment. PET imaging is a perfect area for those interested in clinical studies but also offers the opportunity to discover what happens in a laboratory. I am now an NIHR clinical lecturer at Imperial College.

Paul Shotbolt (2007-2010)

Positron emission tomography (PET) technology can be used to measure striatal dopamine synthesis and release, both of which have been shown to be elevated in schizophrenia. During my PhD I found that striatal dopamine synthesis capacity is not elevated in healthy individuals at genetic risk of schizophrenia, or in well treated stable patients with chronic schizophrenia, suggesting that elevated striatal dopamine synthesis capacity is not a vulnerability marker for schizophrenia and that it is associated with active psychosis only. In addition, no elevation in striatal dopamine synthesis capacity was found in healthy individuals with hallucinations, suggesting that the underlying neurobiology in this group is not the same as in schizophrenia. I also found that the novel PET ligand [11C]-(+)-PHNO is superior to [11C]raclopride for studying acute fluctuations in dopamine in the striatum. Use of [11C]-(+)-PHNO will allow quantification of smaller changes in dopamine release. I am now a consultant psychiatrist at The Maudsley.