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We are working on deciphering how the adaptive immune system can be used as diagnostics and therapeutics. We are investigating how defects in the ability to mount effective immune responses lead to infectious disease susceptibility, impaired surveillance of cancer and immunodeficiencies, compared to the mechanisms leading to a breakdown of immunological tolerance causing autoimmune diseases.

This will lead us to: 

  • understand why certain individuals are at greater risk of developing immunological disease 
  • highlight key interactions of immune cells within sites of inflammation or disease
  • define novel therapeutic targets or optimal therapeutic combinations
  • identify blood biomarkers immune status
  • stratify patients for improved clinical management

This is being achieved through the development and application of novel experimental and computational approaches, working in partnership with a global network of clinicians, immunologists and sample cohorts. 

We prioritise translational- and patient-focussed research to work towards bridging fundamental biology to early phase clinical trials. Our research interests focus on B cell biology and their interactions with other cells in tissues and blood:

 

(1)    development and diversification of different B cell populations in health and disease

(2)    understanding the nature of B cell immuno-surveillance, regulation and activation across cancers and autoimmune diseases

(3)    minimal residual disease detection in lymphoid malignancies

(4)    influence of genetic and environmental variation on B cell fate

(5)    immune cell population reconstitution and persistence with immunomodulatory therapy

(6)    how B and T cells may be therapeutically modulated across diseases

 

Our team

Technology Development

We are developing novel single cell, high-throughput experimental, computational and machine learning tools aimed at probing the immune system function and dysregulation from unique perspectives. Published lab methodologies include: 

  • RECITublet: scRNA-seq doublet/multiplet detection using multi-omic profiling (2020) (https://github.com/rbr1/RECITublet).
  • Isotype-resolved high-throughput BCR sequencing and analyses in humans (Bashford-Rogers, et al., Nature 2019), mice (Burrows, Bashford-Rogers, et al., Nature Immunology, 2020), llamas (McCoy, et al., PLoS Pathog, 2014), and other organisms.
  • High-throughput TCR sequencing and analyses (De Mattos-Arruda et al., Cell Reports, 2019).
  • Ultrasensitive amplicon barcoding for next-generation sequencing facilitating sequence error and amplification-bias correction (Ahmed, et al., Scientific Reports, 2020) (https://github.com/rbr1/sUMI_processing_pipeline).
  • Immune-Repertoire-Network-Generation: open source program that performs population analyses on B and T cell repertoires (2013) (https://github.com/rbr1/Immune_receptor_NETWORK-GENERATION).


LAB NEWS

31/08/2020: Work lead by the fantastic Natalie Burrows (University of Cambridge) et al. is finally out showing the dependence of B cell maturation on the hypoxic response:
Dynamic regulation of HIF-1 activity is essential for normal B cell development (Nature Immunology, 2020)
 
30/07/2020: Great to see the review out about autoantibody-associated encephalitis by Bo Sun and colleagues: 
The B cell immunobiology that underlies CNS autoantibody-mediated diseases (Nature Reviews Neurology, 2020)
 
29/06/2020: Well done Felicia Tucci and previous students Ibrahim Ahmed and Aure Aflaflo on a novel barcoded sequencing method:
Ultrasensitive amplicon barcoding for next-generation sequencing facilitating sequence error and amplification-bias correction (Scientific Reports, 2020)


PRE-PRINTS

Immune responses in pancreatic cancer may be restricted by prevalence of activated regulatory T-cells, dysfunctional CD8+ T-cells, and senescent T-cells (2020)

(https://doi.org/10.1101/2020.06.20.163071)

Shivan Sivakumar,  Enas Abu-Shah,  David Ahern,  Edward H Arbe-Barnes,  Nagina Mangal,  Srikanth Reddy, Aniko Rendek, Alistair Easton, Elke Kurz, Michael Silva,  Lara R Heij, Zahir Soonawalla,  Rachael Bashford-Rogers,  Mark R Middleton,  Michael Dustin

  

Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures (2020)

(https://www.biorxiv.org/content/10.1101/2020.05.20.106294v1)

Jacob D. Galson, Sebastian Schaetzle, Rachael J. M. Bashford-Rogers, Matthew I. J. Raybould, Aleksandr Kovaltsuk, Gavin J. Kilpatrick, Ralph Minter, Donna K. Finch, Jorge Dias, Louisa James, Gavin Thomas, Wing-Yiu Jason Lee, Jason Betley, Olivia Cavlan, Alex Leech,  Charlotte M. Deane, Joan Seoane, Carlos Caldas, Dan Pennington, Paul Pfeffer, Jane Osbourn

 

PUBLICATIONS

Dynamic regulation of HIF-1 activity is essential for normal B cell development (Nature Immunology2020)

https://www.nature.com/articles/s41590-020-0772-8

Natalie Burrows, Rachael J.M. Bashford-Rogers, Vijesh J. Bhute, Ana Peñalver, John R. Ferdinand, Benjamin J. Stewart, Joscelin E.G. Smith, Mukta Deobagkar-Lele, Girolamo Giudice, Thomas M Connor, Akimichi Inaba, Laura Bergamaschi, Sam Smith, Maxine G.B. Tran, Evangelia Petsalaki, Paul A. Lyons, Marion Espeli, Brian J.P. Huntly, Kenneth G.C. Smith, Richard J. Cornall, Menna R. Clatworthy, Patrick H. Maxwell

 

The B cell immunobiology that underlies CNS autoantibody-mediated diseases (Nature Reviews Neurology, 2020)

https://www.nature.com/articles/s41582-020-0381-z

Bo Sun, Melanie Ramberger, Kevin C. O’Connor, Rachael J. M. Bashford-Rogers & Sarosh R. Irani

 

Ultrasensitive amplicon barcoding for next-generation sequencing facilitating sequence error and amplification-bias correction (Scientific Reports, 2020)

https://rdcu.be/b5iBm

Ibrahim Ahmed, Felicia A. Tucci, Aure Aflalo, Kenneth G. C. Smith, Rachael Bashford-Rogers

 

Shared D-J rearrangements reveal cell of origin of TCF3-ZNF384 and PTPN11 mutations in monozygotic twins with concordant BCP-ALL (Blood, 2020)

https://ashpublications.org/blood/article/136/9/1108/461243/Shared-D-J-rearrangements-reveal-cell-of-origin-of

Clara Bueno, Paola Ballerini, Ignacio Varela, Pablo Menendez, Rachael Bashford-Rogers

 

Distinctive binding properties of patient-derived LGI1-autoantibodies determine pathogenicity (Brain2020)

https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awaa104/5841730

Melanie Ramberger,* Antonio Berretta,* Jeanne MM Tan,* Bo Sun, Sophia Michael, Tianrong Yeo, Jakob Theorell, Rachael Bashford-Rogers, Sofija Paneva, Victoria O’Dowd, Neesha Dedi, Sarfaraj Topia, Robert Griffin, Jorge Ramirez-Franco PhD, Oussama El Far, Stéphanie Baulac, Maria I Leite, Arjune Sen, Alexander Jeans, David McMillan,5 Diane Marshall, Daniel Anthony, Daniel Lightwood, Patrick Waters, Sarosh R Irani.

 

B cell receptor repertoire analysis in six immune-mediated diseases (Nature, 2019)

https://www.nature.com/articles/s41586-019-1595-3.pdf

RJM Bashford-Rogers, L Bergamaschi, EF McKinney, DC Pombal, F Mescia, JC Lee, DC Thomas, SM Flint, P Kellam, DRW Jayne, PA Lyons, KGC Smith

 

Natural history and cell-of-origin of TCF3-ZNF384 & PTPN11 mutations in twins with concordant B-ALL (Blood, 2019)

http://www.bloodjournal.org/content/134/11/900

Clara Bueno*, J Ramón Tejedor*, Rachael Bashford-Rogers*,Laura González-Silva*, Rafael Valdés-Mas, Antonio Agraz-Doblás, Rafael Díaz de la Guardia, Chrystele Bilhou-Nabera, Nassera Abermil, Hélène Guermouche, Mario F Fraga, Agustín F Fernández, Paola Ballerini, Ignacio Varela, Pablo Menendez.

 

 The integrated genomic and immune landscapes of lethal metastatic breast cancer. (Cell Reports, 2019) 

https://www.cell.com/cell-reports/pdf/S2211-1247(19)30578-9.pdf

Leticia De Mattos-Arruda, Stephen-John Sammut, Edith M. Ross, Rachael Bashford-Rogers,Erez Greenstein, Havell Markus,  Sandro Morganella, Yvonne Teng, Yosef Maruvka, Bernard Pereira, Oscar Rueda, Suet-Feung Chin, Tania Contente-Cuomo, Regina Mayor, Alexandra Arias, Raza Ali, Wei Cope, Daniel Tiezzi, Dan Reshef,  Elena Martinez, Vicente Peg, Santiago Ramon y Cajal, Javier Cortes, George Vassiliou, Gad Getz, Serena Nik-Zainal, Muhammed Murtaza, Nir Friedman, Florian Markowetz, Joan Seoane and Carlos Caldas 

 

Genetic modification of primary human B cells generates translationally-relevant models of high-grade lymphoma (Nature Communications, 2019 and bioRxiv, 2019

https://rdcu.be/bS05b

Rebecca Caeser, Miriam Di Re, Joanna A Krupka, Jie Gao, Maribel Lara-Chica, João M.L Dias, Susanna L Cooke, Rachel Fenner, Zelvera Usheva, Hendrik Runge, Philip A Beer, Hesham Eldaly, Hyo-Kyung Pak, Chan-Sik Park, George Vassiliou, Brian J.P Huntly, Annalisa Mupo, Rachael JM Bashford-Rogers, Daniel J Hodson

 

FcgRIIb differentially regulates pre-immune and germinal center B cell tolerance in mouse and human. (Nature Communications2019

http://dx.doi.org/10.1038/s41467-019-09434-0

Marion Espeli, Rachael Bashford-Rogers, John Sowerby, Nagham Alouche, Limy Wong, Alice Denton, Michelle Linterman, and Ken Smith

 

Unravelling The Cellular Origin And Clinical Prognostic Markers Of Infant B-Cell Acute Lymphoblastic Leukemia Using Genome-Wide Analysis (Heamatologica, 2019)

http://www.haematologica.org/content/104/6/1176.full.pdf

Antonio Agraz-Doblas, Clara Bueno, Rachael Bashford-Rogers, Anindita Roy, Pauline Schneider, Michela Bardini, Paola Ballerini, Gianni Cazzaniga, Thaidy Moreno, Carlos Revilla, Marta Gut, Maria G Valsecchi, Irene Roberts, Rob Pieters, Paola De Lorenzo, Ignacio Varela, Pablo Menendez, Ronald W Stam

 

Combined influence of B-cell receptor rearrangement and somatic hypermutation on B-cell class-switch fate in health and in chronic lymphocytic leukaemia (Frontiers Immunology, 2018)

https://www.frontiersin.org/articles/10.3389/fimmu.2018.01784/full

Velislava N Petrova, Luke Muir, Paul F McKay, George S Vassiliou, Kenneth GC Smith, Paul A Lyons, Colin A Russell, Carl A Anderson, Paul Kellam, Rachael JM Bashford-Rogers

 

Antibody repertoire analysis in polygenic autoimmune diseases (Immunology, 2018)

Rachael J.M. Bashford-Rogers, Kenneth G.C. Smith and David C. Thomas

 

Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors (Nature Cell Biology, 2017)

Sarah Horton, George Giotopoulos, Haiyang Yun, Shabana Vohra, Olivia Sheppard, Rachael Bashford-Rogers, Mamunur Rashid, Alex Clipson, Wai-In Chan, Daniel Sasca, Loukia Yiangou, Hikari Osaki, Faisal Basheer, Paolo Gallipoli, Natalie Burrows, Aysegul Erdem, Anastasiya Sybirna, Sarah Förster, Wanfeng Zhao, Tonci Sustic, Anna Petrukina Harrison, Elisa Laurenti, Jessica Okosun, Daniel Hodson, Penny Wright, Kenneth Smith, Patrick Maxwell, Jude Fitzgibbon, Ming-Qing Du, David Adams, and Brian Huntly

 

Novel pre/pro-B cells generates macrophage populations during homeostasis and inflammation (PNAS, 2017)

Tatsiana Audzevich, Rachel Bashford-Rogers, Neil A. Mabbott, Dan Frampton, Tom C Freeman, Alexandre Potocnik, Paul Kellam, Derek W Gilroy

 

Dynamic variation of CD5 surface expression levels within individual chronic lymphocytic leukaemia clones (Experimental Hematology2017)

Rachael J. M. Bashford-Rogers, Anne L. Palser, Clare Hodkinson, Joanna Baxter, George A. Follows, George S. Vassiliou, and Paul Kellam.

 

RNA-seq de novo assembly of clonal immunoglobulin rearrangements identifies interesting biology and uncovers prognostic features in multiple myeloma. (Blood, 2016, 128(22); 195)

Mosen-Ansorena D, Bashford-Rogers R, Bolli N, Minvielle S, Magrangeas F, Anderson KC, AveTLoiseau H, Parmigiani G, Munshi NC.

 

Eye on the B ALL: B cell receptor repertoires reveal persistence of numerous B lymphoblastic leukemia subclones from diagnosis to relapse. (Leukemia2016)

Rachael Bashford-Rogers*, Katerina A. Nicolaou*, Jack Bartram, Nicholas J. Goulden, Loizos Loizou, Laura Koumas, Jianxiang Chi, Mike Hubank, Paul Kellam, Paul A. Costeas and George S. Vassiliou.

 

Epstein-Barr virus nuclear protein EBNA3C directly induces expression of AID and somatic mutations in EBV-infected B cells (The Journal of Experimental Medicine2016)

Jens S Kalchschmidt, Rachael Bashford-Rogers, Adam CT Gillman, Kostas Paschos, Paul Kellam and Martin J Allday.

 

Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals (Philosophical Transactions B, 2015)

Kenneth B Hoehn, Astrid Gall, Rachael Bashford-Rogers, SJ Fidler, S Kaye, JN Weber, MO McClure, SPARTAC Trial Investigators, Paul Kellam, Oliver G Pybus.

 

Molecular evolution of broadly neutralizing llama antibodies to the CD4 binding site of HIV-1. (Plos Pathogens 2014)

McCoy, L. E., Rutten, L., Frampton, D., Anderson, I., Granger, L., Bashford-Rogers, R , Webb, B., Dekkers, G., Seaman, M., Koh, W., Wagner, R., Verrips, T., Kellam, P., Fassati, A., and Weiss, R. A.

 

Capturing needles in haystacks: comparison of B cell receptor sequencing methods. (BMC Immunology 2014).

Bashford-Rogers, R., Palser, A, Idris, S, Carter, L, Epstein, M, Callard, R, Douek, D., Vassiliou, G., Follows, G., Hubank, M. and Kellam, P.

 

Network properties derived from deep sequencing of the human B cell receptor repertoires delineates B cell populations. (Genome Research 2013).

Bashford-Rogers, RJM. Palser AL, Huntly BJ, Rance R, Vassiliou GS, Follows GA, Kellam P.

 

Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. (LANCET, 2013).

Cotten M, Watson SJ, Kellam P, Al-Rabeeah AA, Makhdoom HQ, Assiri A, Al-Tawfiq JA, Alhakeem RF, Madani H, Alrabiah FA, Hajjar, S. A., Al-Nassir, W. N., Albarrak, A., Flemban, H., Balkhy, H. H., Alsubaie, S., Palser, A. L., Gall, A., Bashford-Rogers, R., Rambaut, A., Zumla, A. I. & Memish, Z. (2013).

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