Cancer Genomics Group

Here is the link to our new paper, published today in Leukemia. The work outlines a novel putative role for a cluster of micro-RNAs (miRNA) all located at 14q32 in the pathogenesis of chronic lymphocytic leukaemia (CLL). Integrative genomic analysis of miRNA and genome-wide expression data revealed pronounced regulatory potential for these 14q32 miRNAs, potentially accounting for up to 25% of the transcriptome signature associated with immunoglobulin heavy variable gene mutational status. GAB1, a positive regulator of BCR signalling, was potentially regulated by five 14q32 miRNAs and we confirmed that two of these (miR-409-3p and miR-411-3p) significantly repressed activity of the GAB1 3′UTR.
Our analysis demonstrates a potential key role of the 14q32 miRNA locus in the regulation of CLL-related gene regulation.

Network analysis reveals a major role for 14q32 cluster miRNAs in determining transcriptional differences between IGHV-mutated and unmutated CLL - Leukemia Chronic lymphocytic leukaemia (CLL) cells can express unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain (IGHV) genes with differing clinical behaviours, variable B cell receptor (BCR) signalling capacity and distinct transcriptional profiles. As it remains unclear how these differences...

It has been some time since our last post, but here is a link to a recent press release from the University of Southampton, outlining two recent research publications from our team, and from our collaborators.

We worked with colleagues in Southampton, and researchers across 11 academic institutions, 8 different countries and alongside colleagues in Industry. This team examined patient specimens and clinical trial data from 1000’s of patients to assess the importance of immune cell molecules called Fc gamma receptors (FCGRs) in the therapeutic efficacy of two antibody drugs, rituximab and obinutuzumab.

Over the last decade these two antibodies have become the mainstay of many treatments for lymphoma and more recently autoimmune disorders such as rheumatoid arthritis and multiple sclerosis.

role of gamma receptors in cancer antibody drugs | University of Southampton Scientists In Cancer Sciences Have Published Findings Of Their Research Into How Two Important Antibody Drugs Work And Why They Sometimes Fail In Some Patients.

Congratulations Professor Stevenson.

CONGRATULATIONS to Professor Freda Stevenson who has been recognised by the British Society for Haematology
with the Lifetime Achievement Award.

Professor Stevenson has been at the forefront of cancer immunology research for over 40 years, where she has led, shaped and continues to pioneer groundbreaking research in understanding how to engage the immune system to fight lymphoma. She has also used immunogenetics to increase our understanding of how lymphomas develop.

The award honours those whose working life has significantly contributed to the advancement of Haematology.

Read more about Professor Stevenson's achievements here
https://bit.ly/2K44h6m

Here is a link to a talk that I gave last year in Edinburgh at the International Workshop on CLL, nothing less that than the opening, plenary lecture, on the genome of patients with CLL.

Jonathan Strefford – iwCLL 2019 Bio Ascend LLC 980 N Michigan Avenue, Suite 1400 Chicago, IL 60611 (p) 1-888-476-9129 (US toll-free) (f) 312-277-6893 [email protected]

POST 4: CRUK ECRIN-M3 Research Technician

You are invited to apply for the post of Research Technician to work in the Academic Unit of Cancer Sciences’ Laboratories based at the Southampton General Hospital. You will work as part of the international CRUK Accelerator Award ‘Early Cancer Research Initiative Network on Monoclonal B-cell Lymphocytosis (ECRIN-M3)’, awarded to Dr Francesco Forconi, with Prof Jonathan Strefford and Dr Matthew Rose-Zerilli. The candidate will work as part of a multi-disciplinary team investigating the biology of early-stage mature B-cell neoplasms; providing technical laboratory support and will perform single-cell based transcriptomic and ATAC-seq experiments in our 10x Genomics facility. The ultimate aim of the project will be to identify and functionally characterise expression patterns determining progression to overt leukaemia, highlighting potential cancer biomarkers.

https://jobs.soton.ac.uk/Vacancy.aspx?ref=1275320CM

POST 3: CRUK ECRIN-M3 Data Manager in B-cell Malignancies

You will lead in a new clinical research study on the management of the clinical and research data of monoclonal B-cell lymphocytosis (MBL) and other early-stage B cell malignancies, working with data specialists in the Clinical Informatics Research unit and with an expanding team of clinicians and scientists with a strong grounding in cancer B-cell immunology, genomics, molecular/cellular biology and bioinformatics at the School of Cancer Sciences.

Job Opportunity at the University of Southampton: CRUK ECRIN-M3 Data Manager in B-cell Malignancies Applications are invited for a CRUK Data Manager position to join the CRUK accelerator programme ‘Early Cancer Research Initiative Network on Monoclonal B-cell Lymphocytosis (ECRIN-M3) awarded to Dr Francesco Forconi.For personalised medicine...

POST 2: CRUK ECRIN-M3 Post-Doctoral Research Fellow in B-cell Malignancies

You will be an enthusiastic and well-motivated scientist, capable of developing your research project as well as a good team-player with excellent communication skills. You will investigate the mechanisms of disease progression mediated by the B-cell receptor from the very early stages, in B-cell leukaemias and lymphomas. You will join an expanding team of clinicians and scientists with a strong grounding in cancer B-cell immunology, genomics, molecular/cellular biology and bioinformatics. You will also interact with international collaborators, including those from Spain and Italy involved in the ECRIN-M3 programme.

Job Opportunity at the University of Southampton: CRUK ECRIN-M3 Post-Doctoral Research Fellow in B-cell Malignancies Applications are invited for a CRUK Research Fellow position to join the CRUK accelerator programme ‘Early Cancer Research Initiative Network on Monoclonal B-cell Lymphocytosis' (ECRIN-M3) awarded to Dr Francesco Forconi.The successful...

Hi there, just a quick note to say we have some new employment opportunities in our lab. They are all part of the the CRUK Accelerator grant ‘Early Cancer Research Initiative Network on Monoclonal B-cell Lymphocytosis (ECRIN-M3), awarded to Dr Francesco Forconi with Professor Jonathan Strefford.

POST 1: CRUK ECRIN-M3 Senior Research Fellow in B-cell Cancer Bioinformatics

We are now seeking a senior research scientist to investigate single-cell gene expression and chromatin accessibility in normal and malignant immune cells. The candidate will work as part of a multi-disciplinary team investigating the biology of early-stage mature B-cell neoplasms. The successful candidate will analyse next-generation sequencing (NGS)-based expression and ATAC-seq data, at the bulk and single-cell level, with subsequent downstream modelling and molecular studies. The ultimate aim will be to identify and functionally characterize expression patterns determining progression to overt leukaemia, highlighting potential cancer biomarkers.

Job Opportunity at the University of Southampton: CRUK ECRIN-M3 Senior Research Fellow in B-cell Cancer Bioinformatics The School of Cancer Sciences in Southampton, with over 100 scientists, clinicians and associated staff, has a long and distinguished record in the study of Cancer. We are now seeking a senior research scientist to investigate single-cell gene...

Congratulations to Stuart Blakemore, on his new paper, published online today in Leukemia. This work is from his time in Southampton studying for his PhD and outlines a large genomic screen looking for somatic mutations in patients with chronic lymphocytic leukemia (CLL). His work supports the idea that useful information can be gained from sequencing a broader panel of genes for mutations, helping to identify patient groups with different clinical outcomes. Well done Stu!

Clinical significance of TP53, BIRC3, ATM and MAPK-ERK genes in chronic lymphocytic leukaemia: data from the randomised UK LRF CLL4 trial Despite advances in chronic lymphocytic leukaemia (CLL) treatment, globally chemotherapy remains a central treatment modality, with chemotherapy trials representing an invaluable resource to explore disease-related/genetic features contributing to long-term outcomes. In 499 LRF CLL4 cases, a trial w...

Jon Strefford has just visited the city of Adelaide to present a series of lectures, including the Australian Leukaemia and Lymphoma Study Group Annual Meeting. Lovely city and wonderful people.

An evening meal for the Faculty at this years iwCLL meeting, on the Royal Yacht Britannia. Lovely evening, fine wine, fantastic food and great company!

Day 1 of iwCLL begins, with Jon Strefford presenting the opening lecture, covering the genomic landscape of CLL.