Mikhail Spivakov

About me

Experience:

2024 -

Present

Promoted to MRC Programme Leader

2023 -

Present

MRC LMS Athena Swan Lead

2018 -

Present

Honorary Senior Lecturer (Imperial College London)

2018 -

Present

Joined MRC LMS

2012 -

2018

Group Leader (Babraham Institute, Cambridge)

2008 -

2012

EMBL Interdisciplinary Postdoctoral Fellow (EMBL Heidelberg, Germany)

2003 -

2007

PhD Biology/Bioinformatics (Imperial College London/MRC-LMS)

2002 -

2003

MRes Integrative Biomedical Sciences (Imperial College London)

1997 -

2002

Diploma in Virology & Biochemistry (Lomonosov Moscow State University, Russia)

Research focus:

We study how genes are regulated in human cells, particularly when they make decisions to become more specialised or to respond to stimuli, as well as in cancer. We are particularly interested in the "molecular switch" regions on the DNA termed enhancers that turn genes go on and off. We study how these regions are organised and how exactly they control their target genes in time and space. Our research spans multiple scales, from individual enhancer-gene pairs to global gene regulatory networks. Since enhancers often localise some distance away from the genes they control on the DNA, we are particularly interested in the mechanisms of enhancer-promoter communication and use various wet-lab and computational tools to dissect them.

Joined LMS:

2018

About me:

I joined the LMS because of the exciting and rigorous science happening in the institute that complements mine, opening opportunities for collaboration and expanding my horizons. I was also excited by the institute's links with Imperial College and Hammersmith Hospital, which we are already benefitting from in our interdisciplinary work on human biology.

Impact of my work:

Our main focus is on the understanding the basic principles of gene control, which enables translational work in multiple areas, from regenerative medicine to immunology and oncology. Our immediate contribution to translational science lies in using our insights about enhancers and enhancer-gene communication to interpret the function of disease-associated variants that often localise to these regions.

My Research

Functional gene control

The functional gene control group headed by Mikhail Spivakov investigates the logic of gene regulation using a combination of experimental and computational approaches.

VIEW MY RESEARCH GROUP

Selected publications

Lambert J / Oc S, Worssam MD, Häußler D, Figg NL, Baxter R, Foote K, Finigan A, Mahbubani, KT, Bennett MR, Krüger A, Spivakov M, Jørgensen HF. Network-based prioritisation and validation of novel regulators of vascular smooth muscle cell proliferation in disease. Nature Cardiovascular Research, 3, 714–733, 2024

Ray-Jones H, Spivakov M. Transcriptional enhancers and their communication with gene promoters. (2021). Cell Mol Life Sci, doi: 10.1007/s00018-021-03903-w. (A review article).

Freire-Pritchett P* / Ray-Jones H*, Della Rosa M, Eijsbouts C, Orchard WR, Wingett SW, Wallace C, Cairns J, Spivakov M^, Malysheva V^. Detecting chromosomal interactions in Capture Hi-C data with CHiCAGO and companion tools. (2021). Nature Protocols, doi: 10.1038/s41596-021-00567-5.

* joint first authors, ^ joint corresponding authors with a postdoc in the lab.

Watt S, Vasquez L, Walter K, Mann AL, Kundu K, Chen L, Yan Y, Ecker S, Burden F, Farrow S, Farr B, Iotchkova V, Elding H, Mead D, Tardaguila M, Ponstingl H, Richardson D, Datta A, Flicek P, Clarke L, Downes K, Pastinen T, Fraser P, Frontini M, Javierre BM^, Spivakov M^, Soranzo N^. (2021). Genetic perturbation in PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease. Nature Communications 12:2298.

^ joint corresponding authors.

Ho JSY* / Mok BW-Y*, …, Ray-Jones H, Malysheva V, Thiecke MJ, …, Spivakov M, Weirauch MT, Heinz S, Chen H, Benner C, Richt JA, Marazzi I. (2021). TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation. Cell 184, 1–15.

* joint first authors.

Thiecke MJ*/ Wutz G*, Muhar M, Tang W, Bevan S, Malysheva V, Stocsits R, Neumann T, Zuber J, Fraser P, Schoenfelder S, Peters J-M, Spivakov M. (2020). Cohesin-Dependent and -Independent Mechanisms Mediate Chromosomal Contacts between Promoters and Enhancers. Cell Reports 32: 107929.

* joint first authors.

Dobnikar L* / Taylor AL*, Chappell J, Oldach P, Harman JL, Oerton E, Dzierzak E, Bennett MR, Spivakov M^ / Jørgensen HF^. (2018). Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels. Nature Communications 9:4567.

* joint first authors, ^ joint corresponding authors.

Freire-Pritchett P* / Schoenfelder S*, Várnai C, Wingett SW, Cairns J, Collier AJ, García-Vílchez R, Furlan-Magaril M, Osborne CS, Fraser P, Rugg-Gunn PJ^, Spivakov M^. (2017). Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells. eLife 6: e21926.

* joint first authors, ^ joint corresponding authors.

Javierre B-M* / Burren OS* / Wilder SP* / Kreuzhuber R* / Hill SM*, Sewitz S, Cairns J, Wingett SW, Várnai C, Thiecke MJ, Burden F, Farrow S, Cutler AJ, Rehnström K, Downes K, Grassi L, Kostadima M, Freire-Pritchett P, Wang F, The BLUEPRINT Consortium , Stunnenberg HG, Todd JA, Zerbino DR, Stegle O, Ouwehand WH, Frontini M^ / Wallace C^ / Spivakov M^# / Fraser P^. (2016). Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters Cell 167(5), 1369-1384.

* joint first authors, ^ joint corresponding authors, # lead contact.
• Minireview presenting this paper • Interview on Cambridge TV

Cairns J* / Freire-Pritchett P*, Wingett SW, Várnai C, Dimond A, Plagnol V, Zerbino D, Schoenfelder S, Javierre B-M, Osborne C, Fraser P, Spivakov M. (2016). CHiCAGO: Robust Detection of DNA Looping Interactions in Capture Hi-C data. Genome Biology 17(1), 127. PMID: 27306882.

F1000 Prime recommended paper. * joint first authors.

Bolland DJ* / Koohy H*, Wood AL, Matheson LS, Krueger F, Stubbington MJT, Baizan-Edge A, Chovanec P, Stubbs BA, Tabbada K, Andrews SR, Spivakov M^, Corcoran AE^. (2016). Two Mutually Exclusive Local Chromatin States Drive Efficient V(D)J Recombination. Cell Reports 15(11), 2475–2487. PMID: 27264181.

F1000 Prime recommended paper. * joint first authors; ^ joint corresponding authors.

Spivakov M. (2014). Spurious transcription factor binding: Non-functional or genetically redundant? BioEssays 36(8), 798-806. PMID: 24888900.

Junion G* / Spivakov M*, Girardot C, Braun M, Gustafson EH, Birney E, Furlong EE. (2012). A transcription factor collective defines cardiac cell fate and reflects lineage history. Cell 148(3):473-86. PMID: 22304916.

* joint first authors.

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