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MRC Cancer Unit


Dr Alessandro Esposito

Biography | ORCiD (publications) | Group Webpage | The Team





Cellular decisions and cell-to-cell variability in carcinogenesis

At any given time in adulthood, our bodies are made of about 3 trillion cells (blood cells excluded). These cells must continually maintain tissue function — our skin protecting us from the environment, the lungs giving us oxygen, the heart pumping blood through our veins, etcetera. Every day, 1 billion of these cells (a number of cells similar to the number of people living in China, India or twice the number of Europeans) die and have to be replenished. By the end of our lifespan, we shed 30 trillion cells, a number that is 300 times the number of people that have ever inhabited planet Earth. This means that, at any given time, cells have to make choices such as dying, dividing, moving and becoming a different cell type to maintain our bodies. A vast amount of cell decisions is taken at any given moment.

Cancer is the irreversible loss of tissue homeostasis or, in simpler terms, the uncontrolled growth of cells within an organ of our body. Cancer cells stop to abide by the ecological rules set by our bodies. We study how oncogenic signalling cause cells to take decisions outside the rulebook that make our bodies the amazing machines they are.


Non-genetic heterogeneity of cellular decisions. a) The homeostasis of healthy tissues is maintained by biochemical networks that process information from within the cell, the surrounding cells and the microenvironment, to coordinate the most appropriate


We are a groups of physicists, engineers, cell and molecular biologists committed to work across disciplines to address fundamental questions in the following research areas.


Cell-to-cell variability in oncogenesis

We study how different mutant KRAS-alleles reprogram cellular states and cell decisions through quantitative and qualitative alterations of biochemical networks. We investigate the role of cell-to-cell variability and signalling dynamics in the engagement of tumour suppressive mechanisms during acute and chronic activation of oncogenic signalling. We aim to reveal the mechanisms by which heterogeneity of both genetic and non-genetic origin in KRAS-driven cancers synergise to make KRAS-driven tumours an extraordinarily difficult disease to treat.

Cell-to-cell communication in oncogenesis

Cooperation and competition of cellular populations within tissue are fundamental mechanisms underlying tumour initiation and promotion that are not fully understood yet. Using 3D culture systems, including patient-derived samples, and cutting-edge microscopy techniques, we aim to investigate how mutations in KRAS reshape not only cell-autonomous decisions but also homo- and hetero- typic cellular interactions engendering a cancer cell with a fitness advantage. Understanding how cell-to-cell interactions can either suppress or accelerate tumour promotion will improve our capability to stratify risk associated with pre-malignant lesions and to prevent these to progress towards overt cancers.

Technology developments: live single-cell biochemistry

We are breaking new ground in single-cell biochemical imaging to enable the manipulation of cell genetics and cell biochemistry by light, permitting us to trigger oncogenic events with spatiotemporal control in organotypic culture systems, to track cell lineages and fates, cell-to-cell interactions, together with their biochemical determinants.


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Selected publications

The full list of publication and altmetrics is available on our group pages and ORCiD.

  • De S, Campbell CJ, Venkitaraman AR, Esposito A†,*, “Pulsatile MAPK signalling modulates p53 activity to control cell fate decisions at the G2 checkpoint for DNA damage”, Cell Reports 30(7):2083-2093
  • Esposito A* and Venkitaraman AR (2019), “ENHANCING BIOCHEMICAL RESOLUTION BY HYPER-DIMENSIONAL IMAGING MICROSCOPY”, Biophys. J. 116(10):1815-1822
  • Haas KT, Lee M, Esposito A and Venkitaraman AR†,*, “Single-molecule localization microscopy reveals molecular transactions during RAD51 filament assembly at cellular DNA damage sites”, Nucleic Acids Research 46(5):2398–2416
  • Liang H, Esposito A, De S, Ber S, Collin P, Surana U, Venkitaraman AR*, “Homeostatic control of the G2 checkpoint via polo-like kinase 1 engenders non-genetic heterogeneity in its fidelity and timing”, Nat Comms. 5, 4048

Shared first or senior authorship; * Correspondent author