Doctoral Inaugural Lectures

The Doctoral College is at the heart of our postgraduate community and provides support to postgraduates across the University's three Colleges.

These Inaugural Lectures are where the very best of our research degree graduates get the chance to share their work and their passion for research with the University and the public. For the latest Doctoral College news and events, find us on Facebook.

2018-2019

Tuesday 19 March 1700:

Can having diabetes be a good thing? - the role of glucose transporters in abdominal aortic aneurysms

Nikesh Dattani, Specialty Registrar in Vascular Surgery, West Midlands Deanery

Abstract

Abdominal aortic aneurysm (AAA) is associated with significant mortality worldwide. At present, the only treatment involves an operation. Understanding the pathogenesis is important to help develop new drug therapies aimed at slowing aneurysm growth. Diabetes mellitus (DM) has been shown to be negatively associated with AAA however the mechanisms underlying this relationship are poorly understood.

This study first confirmed the robustness of this epidemiological relationship and then, using whole aortic tissue samples (WATS) and aortic smooth muscle cells (AoSMCs) from patients with and without AAA, examined the importance of glucose transporters (GLUTs), a group of proteins responsible for sugar transport across cell membranes, in the pathogenesis of AAA and in explaining the negative relationship between DM and AAA.

Comparing WATS from patients with and without AAA, gene and protein expression of GLUTs were significantly higher in WATS from AAA patients. Comparing AoSMCs from patients with and without AAA, gene expression of GLUTs was similar between groups however GLUT activity was significantly higher in AoSMCs from patients with AAA.

To study the effect of DM on GLUTs, AoSMCs from patients with and without AAA were exposed to increasing levels of hyperglycaemia. Hyperglycaemia was not associated with a significant change in the gene expression of GLUTs however was associated with a significant decrease in GLUT activity selectively in the AoSMCs from AAA patients.

In conclusion, these results suggest that glucose transporters are important in the pathogenesis of AAA and may be involved in regulating the protective effect of DM on AAA. Targeting glucose transporters to slow aneurysm growth merits further investigation.

Biography

Nikesh Dattani is a senior trainee in Vascular and Endovascular Surgery currently working in the West Midlands. His academic interests began in 2005 whilst performing his intercalated BSc in Diabetes and Endocrinology at King's College London in which he was awarded a First Class Honours. After graduating from medical school, he took up an Academic Foundation post at King's College London and subsequently went onto take up an Academic Clinical Fellowship in Vascular Surgery at the University of Leicester. During this time he was successfully awarded a Masters in Research degree as well as the prestigious Circulation Foundation Surgeon Scientist Award which funded him to undertake his MD research investigating the significance of glucose transporters in abdominal aortic aneurysm pathogenesis. This was supervised by Professors Matthew Bown and Robert Sayers and was awarded in 2018 with Distinction. Nikesh Dattani is a founder member of the Vascular and Endovascular Research Network in which he remains actively involved as an executive committee member. He maintains a strong academic interest throughout his clinical practice but is also actively involved in teaching, both at undergraduate and postgraduate levels, including being an Advanced Trauma Life Support instructor. He has won numerous awards during his career including those from the Royal Society of Medicine, Wellcome Trust, NIHR and British Journal of Surgery and has published more than 20 peer-reviewed papers to date.

Studies of Bruton’s tyrosine kinase inhibitors in B-cell malignancies

Harriett Walter, Cancer Research UK Clinical Trials Fellow, Leicester Clinical Trials Unit

Abstract of the talk

Despite significant advances, the prognosis in relapsed/refractory (R/R) B-cell malignancies remains poor. In the Phase I study of the selective Bruton’s Tyrosine Kinase inhibitor (BTKi) tirabrutinib in R/R B-cell malignancies, targeting BTK demonstrated remarkable clinical responses with excellent tolerability in Chronic Lymphocytic Leukaemia and Mantle Cell Lymphoma.  Targeted DNA sequencing demonstrated that no specific pre-treatment mutations (such as mutations in TP53) were associated with a lack of response in CLL.  However, in activated B-cell like diffuse large B-cell lymphoma (ABC DLBCL), only 35% of patients responded to treatment and median duration of response was only 12 weeks.  I will present the clinical results of this trial and results from biological and genetic studies exploring mechanisms of resistance to BTKi in ABC DLBCL.

I will also present an example of a case from the clinic where we have utilised novel therapeutic strategies based on an understanding of disease biology elucidated within the laboratory.

Biography

Having graduated from the University of Birmingham in 2006, I undertook foundation and core medical training in the West Midlands and Oxford Deaneries, prior to undertaking speciality training in medical oncology in Leicester.  During speciality training, I undertook a 3 year clinical research fellowship in Haemato-Oncology within the Ernest and Helen Scott Haematological Research Institute with Professor Dyer, leading to the award of my PhD.  In 2017, I took up a Cancer Research UK Clinical Trials Fellowship and in January 2019 commenced in post as an Associate Professor of Medical Oncology.  I chaired the ECMC Junior Investigators Network Group from 2016-2019 and in 2017 was awarded a national joint NIHR and RCP trainee award for contribution to research.

My clinical focus and expertise is in the delivery of Phase I trials in B cell malignancies and solid tumours where I work with novel cytotoxic agents, small molecule and metabolic inhibitors, antibody drug conjugates and immunotherapies.  My research is focused on drug development and linking clinical with laboratory research within the Haematological Research Institute.

Friday 14 June TBC

Shared and distinct genetic determinants between idiopathic pulmonary fibrosis and other pulmonary traits

Richard Allen

Energy companies and climate change: towards a greener corporate objective?

Lisa Benjamin


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Archive

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Testimonials

Two fantastically clear and confident speakers – was a pleasure to be in the audience!” – DIL Audience Member
“Excellent event. Well done all” – DIL Audience Member
“I was very impressed with both speakers…” – DIL Audience Member
“thank you for all the work you put into running and advertising the lectures tonight, despite my nerves I had a great time and really enjoyed giving my lecture!” – Dr Shane Hussey, DIL Speaker
“thank you so much…for such a wonderful occasion. It was such a privilege to be able to deliver an inaugural lecture..” – DIL Speaker
“the two lectures last night were great!” - Member of the Public
"It was lovely to share my work with such a nice audience” - Academic from School of Education
"Thanks a lot for organising this! I really enjoyed the event" - Academic from School of Business

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