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The University of Southampton
Medicine
Phone:
(023) 8120 5170
Email:
A.Steele@soton.ac.uk

Dr Andrew Steele BSc(Hons), M.Phil, PhD

Associate Professor

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Dr Andrew Steele is Associate Professor within Medicine at the University of Southampton.

Dr Steele obtained his PhD in molecular biology from the University of Hertfordshire in 2003. His first postdoctoral position was in the laboratories of Professor Gillian Tozer and Professor David Shima at Gray Cancer Institute and CR-UK Lincoln’s Inn Fields, where he was involved in a project investigating hypoxia and its effect on vascular branching in human bladder carcinoma. Dr Steele briefly studied viral involvement in Motor Neurone Disease with Dr Garson and Professor Tedder at UCL medical school before moving to the laboratory of Dr RG Wickremasinghe at UCL Cancer Institute in 2004. During this time, he worked closely with Professor Victor Hoffbrand, Dr Archie Prentice and Professor Amit Nathwani to better understand microenvironmental signalling, novel therapeutics and chemotherapy resistance mechanisms in Chronic Lymphocytic Leukaemia (CLL).

Dr Steele moved to the University of Southampton in March 2011 to take up a lectureship position in the Cancer Sciences Unit, within the B cell malignancies group where he collaborated with Professors Graham Packham, Freda Stevenson, Mark Cragg and Jonathan Strefford. He was promoted to Senior Lecturer in 2013 after establishing a Bloodwise funded South Coast tissue biobank with Professor Oscier, which stores with consent, blood samples from patients with lymphoproliferative malignancies. He was subsequently promoted to Associate Professor in 2014 based on his research investigating a role of Interleukin-4 (IL-4) in B cell receptor signalling and the role of autophagy in CLL pathology. Dr Steele works extensively with a number of national and international collaborators within Europe and the USA. Dr Steele has consulted for a number of pharmaceutical companies and performed an industrial sabbatical in 2017/2018 in the USA to better understand small molecule drug discovery and development. During his sabbatical he focused his research on Peripheral T cell Lymphoma (PTCL) and cutaneous T cells lymphoma (CTCL). Dr Steele’s current research focuses on investigating the role of B cell receptor (BCR) and T cell receptor (TCR) signalling and how microenvironmental signals regulate these pathways in B and T cell leukemia/lymphoma. Dr Steele has performed a number of studies with BCR kinase and Bcl-2 family inhibitors alone and in combination and is considered an expert in this area particularly around drug development and cell signalling involved in tumour cell death and survival.

Potential students, postdoctoral scientists or clinician scientists wishing to join his group are encouraged to contact Dr Steele.

 

Research interests

Research interests

Chronic lymphocytic leukaemia (CLL) is currently the most prevalent leukaemia in the western world with a very heterogeneous clinical course. Unfortunately, even with the significant advances over the last 10 years, CLL remains incurable.  Dr Steele’s group works largelty with the clinical staff and patients at Southampton General Hospital, the Royal Bournemouth Hospital and the University of Portsmouth who provide tumour samples for his research. Working on CLL has the advantage that you can directly evaluate the biology of the primary tumours from patient. On average greater than 90% of the peripheral blood mononuclear cells (PBMC) are CLL cells.

Dr Steele’s on-going work uses biochemical approaches to study signal transduction providing insights into the biology of B and T cell malignancies, enabling the identification of novel drugs and strategies to target tumour cells whilst leaving normal healthy tissue alone. Dr Steele’s recent studies fall into three categories;

  1. To understand how activating the B cell receptor (BCR) or T cell receptor (TCR) impacts on the survival and proliferation of B and T cell malignancies.
  2. How signals within the microenvironment of the lymph nodes and bone marrow modify signalling via the BCR and TCR and subsequently protect tumour cells from therapy mediated killing.
  3. Investigate the role of autophagy in these haematological malignancies and how they are regulated by signals within the tumour microenvironment. 

Funding

Dr Steele’s work is currently funded via a Cancer Research UK programme grant with Professors G Packham and J Strefford, and is leading on an additional 5 grants with funding from Kay Kendall leukemia fund (KKLF), Bloodwise, MRC-DTP and a number of pharmaceutical companies.

Current and Previous Projects

The influence of IL-4 and B-cell receptor signalling
Understanding how microenvironmental signals within the different tissue compartments drive CLL biology is instrumental in determining how these cells may respond to therapy. Dr Steele’s group recently demonstrated that interleukin 4 (IL-4), in contrast to other cytokines, was able to augment B cell receptor (BCR) expression and signalling and reduced the effectiveness of BTK and PI3K inhibitors to inhibit this pathway in vitro. Moreover, IL-4 signalling pathways appear important for CLL and other B cell malignancies such as follicular lymphoma particularly within the lymph node tissue and are thought to be associated with the aetiology of these diseases. Dr Steele’s group uses a number of biological and omics based platforms to evaluate the impact of the tumour microenvironment on disease progression and how responses to these signals differ between lymphoid malignancies and subsets of disease.

The role of autophagy
Autophagy is a process of self-eating used to maintain cellular homeostasis and overcome periods of stress by starvation, pathogen invasion and the accumulation of dysfunctional organelles. However, autophagy can also promote tumorigenesis and tumour survival. Dr Steele group is currently investigating the basal levels of autophagy in CLL and how they are regulated by microenvrionmental signals. To better understand the role of autophagy in the pathology of CLL. This project aims to determine the different roles autophagy plays in the metabolic pathways, antigen presentation and its correlation with lymphoid tumour progression and drug-induced killing and resistance, in order to evaluate whether autophagy is a suitable therapeutic target within these malignancies.

BCR kinase and Bcl-2 family inhibitors
Over the last few years major advances in the treatment of CLL have occurred using BCR kinase inhibitors such as Ibrutinib (BTK inhibitor) and idelalisib (PI3K inhibitor) and Bcl-2 family inhibitors such as venetoclax (Bcl-2 inhibitor). However, these drugs are not often curative and patients have already developed resistance to the drugs or have not tolerated these agents. Some studies suggest that patients who become resistant to ibrutinib/venetoclax do poorly and have limited alternative treatment options and therefore urgently require novel treatments or therapeutic strategies. However, many of these resistant mechanisms are little understood. Dr Steele group has been involved in research around BTK, PI3K, SYK and JAK inhibition alone and in combination with Bcl-2 family inhibitors such as Bcl-2, Mcl-1 and Bcl-XL as well as a number of novel targeted agents. Dr Steele’s group is also interested in whether a more individualised approach to the treatment of CLL is required, such that a tumour BCR signalling capacity and Bcl-2 family protein expression may determine the type of therapy to be used.

These strategies will hopefully lead to better treatment options for this currently incurable disease that can target the tumour cells without impacting adversely on the normal tissues within the body.

 

Department(s)

Cancer Sciences

Affiliate Department(s)

Cancer Sciences Research group

South Coast LPD Tissue Bank

Education Lead (Cancer Sciences Unit)

Personal Tutor

Teaching

Research

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Faculty of Medicine Senior Lecturer

Biological Sciences Lectures
BIOL 3043 COURSE “MOLECULAR AND CELLULAR PATHOLOGY”
Lecture 1: Apoptosis
Lecture 2: Apoptosis and cancer

BM4 Lectures
Hypoxia
Cells and Aging

Facilitation
BM5
- Student Selected Units (SSU1)
- HCA module

BM4
- Facilitated Year 1 and Year 2 BM4 students

Biological Sciences and Medicine Projects
- BSc
- MSc
- BmedSci
- MmedSci
- Intercalated PhD project supervision

Dr Andrew Steele
Cancer Sciences Unit (MP 824) Somers Building Faculty of Medicine University of Southampton Southampton General Hospital Tremona Road Southampton SO16 6YD

Room Number: SGH/CSB/MP824

Telephone:(023) 8120 5170
Facsimile:(023) 8120 5152
Email:A.Steele@soton.ac.uk

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