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Dr Simon Mitchell

Dr Simon Mitchell (PhD)

Reader in Cancer Systems Biology
E: S.A.Mitchell@bsms.ac.uk
Location: Medical Research Building, University of Sussex, Falmer BN1 9PX

Areas of expertise: Systems Biology

Research areas: DLBCL and other haematological malignancies. Computational and mathematical modelling. Immunity and inflammation. Cell signalling and cell fate.

Personal website: www.mitchell.science

Twitter handle: @SiFTW

Biography

Based on his training in Computer Science and Mathematics, Simon was awarded a Biotechnology and Biological Sciences Research Council (BBSRC) Studentship to pursue a Systems Biology PhD from the University of Manchester. Following his PhD in 2013, and a brief visiting researcher position at the University of Warwick, Simon undertook postdoctoral training in Prof Alexander Hoffmann’s lab at UCLA (USA). He was awarded a UCLA Collaboratory Fellowship to pursue collaborative research and graduate-level teaching for four consecutive years. Simon has published numerous first-author papers (including in Immunity, PNAS and PLOS Computational Biology), multiple reviews, contributed a chapter describing computational modeling approaches to textbooks of laboratory techniques, and contributed to multiple successfully-funded NIH grants. Driven to use systems biology to translate findings from molecular biology to clinical insight, Simon joined BSMS in 2019. Since then, Simon has obtained a Leukaemia UK John Goldman fellowship and a UKRI Future Leaders Fellowship. He is also a member of the NCRI Lymphoma Science Group.

Research

Simon’s primary research focus is in understanding of how intracellular, molecular signalling networks control immune cell fate, and how misregulation of these molecular networks lead to haematological malignancies. His combination of immunology and haematological training lead to a particular interest in B-cell lymphomas.

Simon combines data across temporal and spatial scales into computational simulations to explore how molecular events (taking <1 second at the nanometre scale) propagate through signalling dynamics and cell-population responses to contribute to whole-body outcomes (taking >1 month at scales of > 1 meter).

Simon has particular interest in the regulation of transcription factor NF-κB and its contribution to cell fate decisions in cancer, immunity and inflammation. His long-term ambition is to develop simulations capable of being parameterized from patient-specific data to be used in the clinic for personalized therapeutic guidance.

He also contributes computational systems biology approaches to many productive collaborations from neuroscience to iron regulation and is always looking for new collaborations where exciting biological questions require novel analytical approaches.

Teaching

Simon is an academic tutor and leads an SSC on human iron regulation.Simon is passionate about making challenging subjects welcoming and engaging through research-led teaching and research supervision. Simon was awarded a UCLA fellowship to teach quantitative, computational skills, where his inclusive and engaging teaching style has taught many biologists and clinicians to write their first lines of computer code. He co-authored guidelines (published in Trends In Immunology) on teaching and training interdisciplinary students in increasingly data-rich environments, and has been invited to share his insight at international conferences.

Selected publications

Cloete, I., Smith, V.M., Jackson, R.A. et al. Computational modeling of DLBCL predicts response to BH3-mimetics. npj Syst Biol Appl 9, 23 (2023). https://doi.org/10.1038/s41540-023-00286-5

Jayawant E, Pack A, Clark H, Kennedy E, Ghodke A, Jones J, Pepper C, Pepper A and Mitchell S (2023) NF-κB fingerprinting reveals heterogeneous NF-κB composition in diffuse large B-cell lymphoma. Front. Oncol. 13:1181660. doi: 10.3389/fonc.2023.1181660

O’Donnell A, Pepper C, Mitchell S and Pepper A (2023) NF-kB and the CLL microenvironment. Front. Oncol. 13:1169397. doi: 10.3389/fonc.2023.1169397

Mitchell, Simon et al. ,The NF-κB multidimer system model: A knowledge base to explore diverse biological contexts.Sci. Signal.16,eabo2838(2023). DOI:10.1126/scisignal.abo2838

Agnarelli, A, Mitchell, S, Caalim, G, et al. Dissecting the impact of bromodomain inhibitors on the Interferon Regulatory Factor 4-MYC oncogenic axis in multiple myeloma. Hematol Oncol. 2022; 40( 3): 417- 429. https://doi.org/10.1002/hon.3016

Burley, T.A.; Hesketh, A.; Bucca, G.; Kennedy, E.; Ladikou, E.E.; Towler, B.P.; Mitchell, S.; Smith, C.P.; Fegan, C.; Johnston, R.; et al. Elucidation of Focal Adhesion Kinase as a Modulator of Migration and Invasion and as a Potential Therapeutic Target in Chronic Lymphocytic Leukemia. Cancers 2022, 14, 1600. https://doi.org/10.3390/cancers14071600

Burley, T.A.; Kennedy, E.; Broad, G.; Boyd, M.; Li, D.; Woo, T.; West, C.; Ladikou, E.E.; Ashworth, I.; Fegan, C.; et al. Targeting the Non-Canonical NF-κB Pathway in Chronic Lymphocytic Leukemia and Multiple Myeloma. Cancers 2022, 14, 1489. https://doi.org/10.3390/cancers14061489

Samarasinghe, R.A., Miranda, O.A., Buth, J.E. et al. Identification of neural oscillations and epileptiform changes in human brain organoids. Nat Neurosci 24, 1488–1500 (2021). https://doi.org/10.1038/s41593-021-00906-5

Mitchell, Simon (2021) What will B will B: identifying molecular determinants of diverse B-cell fate decisions through systems biology. Frontiers in Cell and Developmental Biology, 8. a616592 1-8. ISSN 2296-634X

Kennedy, Emma, Coulter, Eve Marie, Halliwell, Emma, Profitos-Peleja, Nuria, Walsby, Elisabeth, Clark, Barnaby, Phillips, Elizabeth H, Burley, Thomas A, Mitchell, Simon, Devereux, Stephen, Jones, Christopher Iain, Johnston, Rosalynd, Chevassut, Timothy J, Pepper, Chris, Pepper, Andrea G S and others, (2021) TLR9 expression in Chronic Lymphocytic Leukemia identifies a pro-migratory subpopulation and novel therapeutic target. Blood. pp. 1-32. ISSN 0006-4971

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