Artem Lomakin

Heidelberg, Germany

I am nearing the completion of my PhD at the University of Cambridge, that is shared between EMBL-EBI, Wellcome Sanger Institute, and DKFZ. My research has been advised by Moritz Gerstung and Lucy R. Yates.

My scientific work brings together recent advancements in spatial genomics technologies and Bayesian data modelling. By collecting diverse data modalities, I aim to integrate information on the genotype, phenotype and spatial environment - the essential triad for elucidating cell behaviour from an evolutionary standpoint. This approach offers a deep understanding of cancer progression within an individual and promises to shed light on the fundamental questions of cancer development:

How much of tumour heterogeneity is attributed to the irreversible state changes caused by mutations vs reversible cell plasticity?
How do cancer cells evolve within the constraints of the native tissue environment?
Why do some cancer evolutionary branches lead to the disease progression while others remain dormant?

Beyond cancer biology, I’m broadly interested in understanding the mechanisms of cellular plasticity and somatic evolution in natural tissues. While cancer is a prominent example of a disease with a strong genetic component, it is just one of many deregulations that arise from a cascade of cellular and tissue-level changes triggered by ageing. Given my computational background, I hope to design algorithms for modelling and potentially reversing age-related diseases. My aspiration is to create a comprehensive multimodal dataset for constructing a unified cell model that links phenotypic and genetic changes with cell signalling. Acknowledging limited resources, I also prioritise hypothesis-driven research and the creation of specialised algorithms for specific challenges.

In addition to my main research activities, I take pleasure in exploring fun little projects and try to document them in my blog.

Latest posts

Nov 25, 2023	Inference of human population history from a single genome

Selected publications

Spatial biology of cancer evolution

Zaira Seferbekova*, Artem Lomakin*, Lucy R Yates, and Moritz Gerstung

Nat. Rev. Genet., May 2023

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The natural history of cancers can be understood through the lens of evolution given that the driving forces of cancer development are mutation and selection of fitter clones. Cancer growth and progression are spatial processes that involve the breakdown of normal tissue organization, invasion and metastasis. For these reasons, spatial patterns are an integral part of histological tumour grading and staging as they measure the progression from normal to malignant disease. Furthermore, tumour cells are part of an ecosystem of tumour cells and their surrounding tumour microenvironment. A range of new spatial genomic, transcriptomic and proteomic technologies offers new avenues for the study of cancer evolution with great molecular and spatial detail. These methods enable precise characterizations of the tumour microenvironment, cellular interactions therein and micro-anatomical structures. In conjunction with spatial genomics, it emerges that tumours and microenvironments co-evolve, which helps explain observable patterns of heterogeneity and offers new routes for therapeutic interventions.
Spatial genomics maps the structure, nature and evolution of cancer clones

Artem Lomakin*, Jessica Svedlund*, Carina Strell, Milana Gataric, Artem Shmatko, Gleb Rukhovich, Jun Sung Park, Young Seok Ju, Stefan Dentro, Vitalii Kleshchevnikov, Vasyl Vaskivskyi, Tong Li, Omer Ali Bayraktar, Sarah Pinder, Andrea L Richardson, Sandro Santagata, Peter J Campbell, Hege Russnes, Moritz Gerstung, Mats Nilsson, and Lucy R Yates

Nature, Nov 2022

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Genome sequencing of cancers often reveals mosaics of different subclones present in the same tumour1-3. Although these are believed to arise according to the principles of somatic evolution, the exact spatial growth patterns and underlying mechanisms remain elusive4,5. Here, to address this need, we developed a workflow that generates detailed quantitative maps of genetic subclone composition across whole-tumour sections. These provide the basis for studying clonal growth patterns, and the histological characteristics, microanatomy and microenvironmental composition of each clone. The approach rests on whole-genome sequencing, followed by highly multiplexed base-specific in situ sequencing, single-cell resolved transcriptomics and dedicated algorithms to link these layers. Applying the base-specific in situ sequencing workflow to eight tissue sections from two multifocal primary breast cancers revealed intricate subclonal growth patterns that were validated by microdissection. In a case of ductal carcinoma in situ, polyclonal neoplastic expansions occurred at the macroscopic scale but segregated within microanatomical structures. Across the stages of ductal carcinoma in situ, invasive cancer and lymph node metastasis, subclone territories are shown to exhibit distinct transcriptional and histological features and cellular microenvironments. These results provide examples of the benefits afforded by spatial genomics for deciphering the mechanisms underlying cancer evolution and microenvironmental ecology.