Khaled Group
Professor Walid Khaled
Epithelial cell fate and tumour development
Email: wtk22@cam.ac.uk | Departmental Affiliation: Department of Pharmacology
Laboratory Location: Department of Pharmacology
Research
Research Focus: Over the last ten years, Professor Khaled has established an ambitious research programme focusing on studying the early cellular and molecular changes associated with tumour initiation. His lab’s ultimate aim is to translate these discoveries into novel cancer detection and prevention methods. He has been awarded several grants, including two competitive fellowships from CRUK - Career Establishment Award (2014-2021) and Programme Foundation Award (2021-2027). During this period, his lab made significant contributions to the field, some of which are highlighted below.
His contributions to the field include making all the sequencing data generated in the lab publicly available through easy-to-use websites. He also shares the lab’s protocols through his website and some cases through youtube videos (eg. single cell prep for the human breast cell atlas).
Based on their single cell work in mouse and human they have identified several pathways that are associated with precancerous cellular changes in the women at high risk of breast cancer. This includes the observation that immune cells in the healthy breast tissue from BRCA1/2 high risk women exhibit an exhausted phenotype. These dysfunctional immune cells are normally only found at latestage tumours. With further funding from CRUK they started a pre-clinical trial to assess the efficacy of these drug paving the way to window of opportunity trials in human.
Key Publications:
- Reed A, Pensa S, Steif A, Stenning J, Kunz D, He P, Twigger AJ, Kania K, Barrow-McGee R, Goulding I, Gomm J, Jones L, Marioni JC, Khaled WT. A single-cell atlas enables mapping of homeostatic cellular shifts in the adult human breast. Nat Genet 56, 652–662 (2024). https://doi.org/10.1038/s41588-024-01688-9
- Twigger AJ, Engelbrecht LK, Bach K, Schultz-Pernice I, Pensa S, Stenning J, Petricca S, Scheel CH, Khaled WT. Transcriptional changes in the mammary gland during lactation revealed by single cell sequencing of cells from human milk. Nat Commun. 2022 Jan 28;13(1):562. Doi: 10.1038/s41467021-27895-0. PMID: 35091553; PMCID: PMC8799659.
- Bach K, Pensa S, Zarocsinceva M, Kania K, Stockis J, Pinaud S, Lazarus KA, Shehata M, Simões BM, Greenhalgh AR, Howell SJ, Clarke RB, Caldas C, Halim TYF, Marioni JC, Khaled WT. Time-resolved single-cell analysis of Brca1 associated mammary tumourigenesis reveals aberrant differentiation of luminal progenitors. Nat Commun. 2021 Mar 9;12(1):1502. Doi: 10.1038/s41467021-21783-3. PMID: 33686070; PMCID: PMC7940427.
- Hadi F, Kulaberoglu Y, Lazarus KA, Bach K, Ugur R, Beattie P, Smith ESJ, Khaled WT. Transformation of naked mole-rat cells. Nature. 2020 Jul;583(7814):E1-E7. Doi: 10.1038/s41586-020-2410-x. Epub 2020 Jul 1. PMID: 32612221.
- Lazarus KA, Hadi F, Zambon E, Bach K, Santolla MF, Watson JK, Correia LL, Das M, Ugur R, Pensa S, Becker L, Campos LS, Ladds G, Liu P, Evan GI, McCaughan FM, Le Quesne J, Lee JH, Calado D, Khaled WT. BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma. Nat Commun. 2018 Aug 20;9(1):3327. Doi: 10.1038/s41467-018-05790-5. PMID: 30127402; PMCID: PMC6102279.
- Bach K, Pensa S, Grzelak M, Hadfield J, Adams DJ, Marioni JC, Khaled WT. Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing. Nat Commun. 2017 Dec 11;8(1):2128. Doi: 10.1038/s41467-017-02001-5. PMID: 29225342; PMCID: PMC5723634.