Lymphocyte somatic evolution for improved cancer treatment
Our lab studies the somatic evolution of the adaptive immune system to address crucial questions in cancer immunology and immune ageing. In cancer, we seek to elucidate the timing and dynamics of the immune response to tumours, how chronic inflammation remodels the immune system to facilitate cancer progression, and the action of immunotherapies on T-cell clonotypes. We aim to use these studies to enhance cancer treatment and patient outcomes. Our work on immune ageing delves into the genomic and phenotypic characteristics of T-cell immunosenescence and their implications for disease progression. Combining cutting-edge techniques in single-cell multiomics and phylogenetic lineage tracing, our research strives to understand how immune and non-immune cells co-evolve and contribute to cancer progression and ageing.
We are in the Department of Pathology at the University of Cambridge, in the heart of Cambridge, UK. We welcome inquiries from interested scientists at any level.
Lab website: www.machado-lab.org.
Key publications
H. E. Machado, N. F. Øbro, N. Williams, S. Tan, A. Z. Boukerrou, M. Davies, M. Belmonte, E. Mitchell, E. J. Baxter, N. Mende, A. Clay, P. Ancliff, J. Köglmeier, S. B. Killick, A. Kulasekararaj, S. Meyer, E. Laurenti, P. J. Campbell, D. G. Kent, J. Nangalia, A. J. Warren, Convergent somatic evolution commences in utero in a germline ribosomopathy. Nat Commun. 14, 5092 (2023).
H. E. Machado, E. Mitchell, N. F. Øbro, K. Kübler, M. Davies, D. Leongamornlert, A. Cull, F. Maura, M. A. Sanders, A. T. J. Cagan, C. McDonald, M. Belmonte, M. S. Shepherd, F. A. Vieira Braga, R. J. Osborne, K. Mahbubani, I. Martincorena, E. Laurenti, A. R. Green, G. Getz, P. Polak, K. Saeb-Parsy, D. J. Hodson, D. G. Kent, P. J. Campbell, Diverse mutational landscapes in human lymphocytes. Nature. 608, 724–732 (2022).
E. Mitchell, M. Spencer Chapman, N. Williams, K. J. Dawson, N. Mende, E. F. Calderbank, H. Jung, T. Mitchell, T. H. H. Coorens, D. H. Spencer, H. Machado, H. Lee-Six, M. Davies, D. Hayler, M. A. Fabre, K. Mahbubani, F. Abascal, A. Cagan, G. S. Vassiliou, J. Baxter, I. Martincorena, M. R. Stratton, D. G. Kent, K. Chatterjee, K. S. Parsy, A. R. Green, J. Nangalia, E. Laurenti, P. J. Campbell, Clonal dynamics of haematopoiesis across the human lifespan. Nature. 606, 343–350 (2022).
H. E. Machado, A. O. Bergland, R. Taylor, S. Tilk, E. Behrman, K. Dyer, D. K. Fabian, T. Flatt, J. González, T. L. Karasov, B. Kim, I. Kozeretska, B. P. Lazzaro, T. J. Merritt, J. E. Pool, K. O’Brien, S. Rajpurohit, P. R. Roy, S. W. Schaeffer, S. Serga, P. Schmidt, D. A. Petrov, Broad geographic sampling reveals the shared basis and environmental correlates of seasonal adaptation in Drosophila. eLife. 10, e67577 (2021).
F. Abascal, L. M. R. Harvey, E. Mitchell, A. R. J. Lawson, S. V. Lensing, P. Ellis, A. J. C. Russell, R. E. Alcantara, A. Baez-Ortega, Y. Wang, E. J. Kwa, H. Lee-Six, A. Cagan, T. H. H. Coorens, M. S. Chapman, S. Olafsson, S. Leonard, D. Jones, H. E. Machado, M. Davies, N. F. Øbro, K. T. Mahubani, K. Allinson, M. Gerstung, K. Saeb-Parsy, D. G. Kent, E. Laurenti, M. R. Stratton, R. Rahbari, P. J. Campbell, R. J. Osborne, I. Martincorena, Somatic mutation landscapes at single-molecule resolution. Nature. 593, 405–410 (2021).
H. E. Machado, D. S. Lawrie, D. A. Petrov, Pervasive Strong Selection at the Level of Codon Usage Bias in Drosophila melanogaster. Genetics. 214, 511–528 (2020).
Tovy, J. M. Reyes, M. C. Gundry, L. Brunetti, H. Lee-Six, M. Petljak, H. J. Park, A. G. Guzman, C. Rosas, A. R. Jeffries, E. Baple, J. Mill, A. H. Crosby, V. Sency, B. Xin, H. E. Machado, D. Castillo, J. N. Weitzel, W. Li, M. R. Stratton, P. J. Campbell, H. Wang, M. A. Sanders, M. A. Goodell, Tissue-Biased Expansion of DNMT3A-Mutant Clones in a Mosaic Individual Is Associated with Conserved Epigenetic Erosion. Cell Stem Cell. 27, 326-335.e4 (2020).
Group Leader - Principal Investigator
Dr Heather Machado
Group Members
Research Associate
PhD Student
PhD Student