Dr Heather Machado

I am interested in the role of the adaptive immune system in ageing and disease, particularly cancer. My background is in evolutionary genomics, having studied population genomics and genome evolution during my PhD at Stanford University and somatic genomics during my postdoc at the Wellcome Sanger Institute. I approach this from the lens of somatic evolution. I use somatic mutations and evolutionary genetic methods to study the co-evolution of immune and non-immune cells, elucidating the role of the adaptive immune system in cancer progression and ageing.

 

 

Research group focus

 

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 T-cell immunosenescence's genomic and phenotypic characteristics and the 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.

 

 

 

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).

S. C. P. Renn, H. E. Machado, N. Duftner, A. K. Sessa, R. M. Harris, H. A. Hofmann, Gene expression signatures of mating system evolution. Genome (2017).

H. E. Machado, A. O. Bergland, K. R. O’Brien, E. L. Behrman, P. S. Schmidt, D. A. Petrov, Comparative population genomics of latitudinal variation in Drosophila simulans and Drosophila melanogaster. Molecular Ecology. 25, 723–740 (2016).

H. E. Machado, G. Jui, D. A. Joyce, C. R. Reilly, D. H. Lunt, S. C. Renn, Gene duplication in an African cichlid adaptive radiation. BMC Genomics. 15, 161 (2014).

J. R. Adrion, A. Kousathanas, M. Pascual, H. J. Burrack, N. M. Haddad, A. O. Bergland, H. Machado, T. B. Sackton, T. A. Schlenke, M. Watada, D. Wegmann, N. D. Singh, Drosophila suzukii: The Genetic Footprint of a Recent, Worldwide Invasion. Mol Biol Evol. 31, 3148–3163 (2014).

S. C. P. Renn, H. E. Machado, A. Jones, K. Soneji, R. J. Kulathinal, H. A. Hofmann, Using comparative genomic hybridization to survey genomic sequence divergence across species: a proof-of-concept from Drosophila. BMC Genomics. 11, 271 (2010).

H. E. Machado, S. C. P. Renn, A critical assessment of cross-species detection of gene duplicates using comparative genomic hybridization. BMC Genomics. 11, 304 (2010).

H. E. Machado, M. B. Cruzan, Intraspecific variation in gene expression under prolonged drought in Piriqueta hybrids and their parental taxa. Plant Science. 178, 429–439 (2010).