Biography
Adam Wilkinson is a Krishnan-Ang Distinguished Scholar and Group Leader in the Department of Haematology and Cambridge Stem Cell Institute. After completing his undergraduate degree at the University of Oxford, he undertook PhD training at the University of Cambridge Department of Haematology with Professor Bertie Göttgens. He then performed postdoctoral training with Professor Hiromitsu Nakauchi at the University of Tokyo and Stanford University with funding from the National Institutes of Health, the Leukemia and Lymphoma Society, Blood Cancer UK, the Japan Society for the Promotion of Science and Edward P. Evans Foundation. He started his own lab in 2021 at the MRC Weatherall Institute of Molecular Medicine at the University of Oxford with support from the Kay Kendall Leukaemia Fund and the NIHR, and was promoted to Associate Professor in 2023. In 2025, he moved back to Cambridge with support from the Krishnan-Ang Foundation and the Wellcome Trust.
Description of Research
Haematopoietic stem cells (HSCs) are critical for human health and disease treatment. HSCs are a rare stem cell population that can generate all the cells of the blood and immune system. Many blood and immune cells are short-lived and must be continuously produced in huge numbers (~2 million per second) throughout our lives. Abnormalities in blood production are common and underlie a number of serious human diseases including blood cancers, anaemias and immunodeficiencies. Despite their importance, the paucity of HSCs and lack of tractable ex vivo HSC culture systems means that the mechanisms that regulate HSC activity are incompletely understood.
HSCs are also used in clinic therapy with HSC transplantation therapy currently representing the only curative treatment option for numerous haematological malignancies. Additionally, HSC-based gene therapies are being developed and used to correct various hereditary blood diseases. While potentially curative, these HSC transplantation therapies still represent a high-risk procedure and are not available to all patients. We are aiming to improve the safety, availability and potential applications of HSC-based therapies through developing new tools to expand and modify HSCs ex vivo.
Towards this goal, we have pioneered new methods to expand transplantable HSCs long-term ex vivo (Wilkinson et al, Nature, 2019; Igarashi et al, Blood Advances, 2023; Sakurai et al, Nature, 2023) and to evaluate the consequences of CRISPR/Cas9 gene editing on functional HSCs in transplantation models (Wilkinson et al, Nature Communications, 2021; Becker et al, Cell Stem Cell, 2023).
The Wilkinson laboratory is currently leveraging this technology to (1) investigate the molecular regulation of HSC self-renewal and lineage commitment, (2) better understand how HSC dysfunction can drive blood cancer initiation, and (3) develop novel HSC-based therapies.
If you are interested in working with us, please contact us at acw63@cam.ac.uk. We are always looking for smart, motivated people to join our team.
Publications
Charlesworth CT, Homma S, Amaya AK, Dib C, Vaidyanathan S, Tan TK, Miyauchi M, Nakauchi Y, Suchy FP, Wang S, Igarashi KJ, Cromer MK, Dudek AM, Amorin A, Czechowicz A, Wilkinson AC, Nakauchi H. Highly efficient in vivohematopoietic stem cell transduction using an optimized self-complementary adeno-associated virus. Mol Ther Methods Clin Dev. 2025 Feb 21;33(1):101438. doi: 10.1016/j.omtm.2025.101438.
Niizuma K, Morikawa S, Gars E, Xiang J, Matsubara-Takahashi T, Saito R, Takematsu E, Wang Y, Xu H, Wakimoto A, Tan TK, Kubota Y, Chan CKF, Weissman IL, Nakagawa T, Wilkinson AC, Nakauchi H, Yamamoto R. Elevated hematopoietic stem cell frequency in mouse alveolar bone marrow. Stem Cell Reports. 2025 Jan 14;20(1):102374. doi: 10.1016/j.stemcr.2024.11.004.
Chan YY, Ho PY, Dib C, Swartzrock L, Rayburn M, Willner H, Ko E, Ho K, Down JD, Wilkinson AC, Nakauchi H, Denis M, Cool T, Czechowicz A. Targeted hematopoietic stem cell depletion through SCF-blockade. Stem Cell Res Ther. 2024 Oct 29;15(1):387. doi: 10.1186/s13287-024-03981-0.
Wilkinson AC, de Bruijn MFTR. A developmental route to hematopoietic stem cells. Nat Biotechnol. 2024 Sep 18. doi: 10.1038/s41587-024-02398-7.
Suchy FP, Karigane D, Nakauchi Y, Higuchi M, Zhang J, Pekrun K, Hsu I, Fan AC, Nishimura T, Charlesworth CT, Bhadury J, Nishimura T, Wilkinson AC, Kay MA, Majeti R, Nakauchi H. Genome engineering with Cas9 and AAV repair templates generates frequent concatemeric insertions of viral vectors. Nat Biotechnol. 2025 Feb;43(2):204-213. doi: 10.1038/s41587-024-02171-w.
Wilkinson AC. Take the MYC to expand blood stem cells. Blood. 2024 Mar 7;143(10):838-840. doi: 10.1182/Blood.2024023827.
Meaker GA, Wilkinson AC. Ex vivo hematopoietic stem cell expansion technologies: recent progress, applications, and open questions. Exp Hematol. 2024 Feb;130:104136. doi: 10.1016/j.exphem.2023.12.001.
Lenders NF, Earls PE, Wilkinson AC, Costin M, Hofer M, Shein TT, Harvey RJ, Krishnan G, Picallo M, Pal A, Wass J, McCormack AI. Predictors of pituitary tumour behaviour: an analysis from long-term follow-up in 2 tertiary centres. Eur J Endocrinol. 2023 Jul 20;189(1):106-114. doi: 10.1093/ejendo/lvad079.
Becker HJ, Ishida R, Wilkinson AC, Kimura T, Lee MSJ, Coban C, Ota Y, Tanaka Y, Roskamp M, Sano T, Tojo A, Kent DG, Yamazaki S. Controlling genetic heterogeneity in gene-edited hematopoietic stem cells by single-cell expansion. Cell Stem Cell. 2023 Jul 6;30(7):987-1000.e8. doi: 10.1016/j.stem.2023.06.002.
Bozhilov YK, Hsu I, Brown EJ, Wilkinson AC. In Vitro Human Haematopoietic Stem Cell Expansion and Differentiation. Cells. 2023 Mar 14;12(6):896. doi: 10.3390/cells12060896.
Khoo HM, Meaker GA, Wilkinson AC. Ex Vivo Expansion and Genetic Manipulation of Mouse Hematopoietic Stem Cells in Polyvinyl Alcohol-Based Cultures. J Vis Exp. 2023 Feb 10;(192). doi: 10.3791/64791.
Sakurai M, Ishitsuka K, Ito R, Wilkinson AC, Kimura T, Mizutani E, Nishikii H, Sudo K, Becker HJ, Takemoto H, Sano T, Kataoka K, Takahashi S, Nakamura Y, Kent DG, Iwama A, Chiba S, Okamoto S, Nakauchi H, Yamazaki S. Chemically defined cytokine-free expansion of human haematopoietic stem cells. Nature. 2023 Mar;615(7950):127-133. doi: 10.1038/s41586-023-05739-9.
Igarashi KJ, Kucinski I, Chan YY, Tan TK, Khoo HM, Kealy D, Bhadury J, Hsu I, Ho PY, Niizuma K, Hickey JW, Nolan GP, Bridge KS, Czechowicz A, Gottgens B, Nakauchi H, Wilkinson AC. Physioxia improves the selectivity of hematopoietic stem cell expansion cultures. Blood Adv. 2023 Jul 25;7(14):3366-3377. doi: 10.1182/bloodadvances.2023009668.
Bloom M, Malouf C, Rodriguez-Fraticelli A, Wilkinson AC, Sankaran VG, Cvejic A. Exploiting somatic mutations to decipher human blood production: a natural lineage-tracing strategy. Exp Hematol. 2023 May;121:2-5. doi: 10.1016/j.exphem.2023.01.005.
Che JLC, Bode D, Kucinski I, Cull AH, Bain F, Becker HJ, Jassinskaja M, Barile M, Boyd G, Belmonte M, Zeng AGX, Igarashi KJ, Rubio-Lara J, Shepherd MS, Clay A, Dick JE, Wilkinson AC, Nakauchi H, Yamazaki S, Göttgens B, Kent DG. Identification and characterization of in vitro expanded hematopoietic stem cells. EMBO Rep. 2022 Oct 6;23(10):e55502. doi: 10.15252/embr.202255502.
Suchy FP, Nishimura T, Seki S, Wilkinson AC, Higuchi M, Hsu I, Zhang J, Bhadury J, Nakauchi H. Streamlined and quantitative detection of chimerism using digital PCR. Sci Rep. 2022 Jun 17;12(1):10223. doi: 10.1038/s41598-022-14467-5.
Charlesworth CT, Hsu I, Wilkinson AC, Nakauchi H. Immunological barriers to haematopoietic stem cell gene therapy. Nat Rev Immunol. 2022 Dec;22(12):719-733. doi: 10.1038/s41577-022-00698-0.
Haltalli MLR, Wilkinson AC, Rodriguez-Fraticelli A, Porteus M. Hematopoietic stem cell gene editing and expansion: State-of-the-art technologies and recent applications. Exp Hematol. 2022 Mar;107:9-13. doi: 10.1016/j.exphem.2021.12.399.
Malouf C, Loughran SJ, Wilkinson AC, Shimamura A, Río P. Translational research for bone marrow failure patients. Exp Hematol. 2022 Jan;105:18-21. doi: 10.1016/j.exphem.2021.11.004.
Sudo K, Yamazaki S, Wilkinson AC, Nakauchi H, Nakamura Y. Polyvinyl alcohol hydrolysis rate and molecular weight influence human and murine HSC activity ex vivo. Stem Cell Res. 2021 Oct;56:102531. doi: 10.1016/j.scr.2021.102531.
Ochi K, Morita M, Wilkinson AC, Iwama A, Yamazaki S. Non-conditioned bone marrow chimeric mouse generation using culture-based enrichment of hematopoietic stem and progenitor cells. Nat Commun. 2021 Jun 11;12(1):3568. doi: 10.1038/s41467-021-23763-z.
Lenders NF, Wilkinson AC, Wong SJ, Shein TT, Harvey RJ, Inder WJ, Earls PE, McCormack AI. Transcription factor immunohistochemistry in the diagnosis of pituitary tumours. Eur J Endocrinol. 2021 May 10;184(6):891-901. doi: 10.1530/EJE-20-1273.
Wilkinson AC, Dever DP, Baik R, Camarena J, Hsu I, Charlesworth CT, Morita C, Nakauchi H, Porteus MH. Cas9-AAV6 gene correction of beta-globin in autologous HSCs improves sickle cell disease erythropoiesis in mice. Nat Commun. 2021 Jan 29;12(1):686. doi: 10.1038/s41467-021-20909-x.
Sommerkamp P, Mercier FE, Wilkinson AC, Bonnet D, Bourgine PE. Engineering human hematopoietic environments through ossicle and bioreactor technologies exploitation. Exp Hematol. 2021 Feb;94:20-25. doi: 10.1016/j.exphem.2020.11.008.
Zaro BW, Noh JJ, Mascetti VL, Demeter J, George B, Zukowska M, Gulati GS, Sinha R, Flynn RA, Banuelos A, Zhang A, Wilkinson AC, Jackson P, Weissman IL. Proteomic analysis of young and old mouse hematopoietic stem cells and their progenitors reveals post-transcriptional regulation in stem cells. Elife. 2020 Nov 25;9:e62210. doi: 10.7554/eLife.62210.
Carrelha J, Lin DS, Rodriguez-Fraticelli AE, Luis TC, Wilkinson AC, Cabezas-Wallscheid N, Tremblay CS, Haas S. Single-cell lineage tracing approaches in hematology research: technical considerations. Exp Hematol. 2020 Sep;89:26-36. doi: 10.1016/j.exphem.2020.07.007.
Loughran SJ, Haas S, Wilkinson AC, Klein AM, Brand M. Lineage commitment of hematopoietic stem cells and progenitors: insights from recent single cell and lineage tracing technologies. Exp Hematol. 2020 Aug;88:1-6. doi: 10.1016/j.exphem.2020.07.002.
Wilkinson AC, Nakauchi H. Stabilizing hematopoietic stem cells in vitro. Curr Opin Genet Dev. 2020 Oct;64:1-5. doi: 10.1016/j.gde.2020.05.035.
Wilkinson AC, Igarashi KJ, Nakauchi H. Haematopoietic stem cell self-renewal in vivo and ex vivo. Nat Rev Genet. 2020 Sep;21(9):541-554. doi: 10.1038/s41576-020-0241-0.
Yamamoto R, Wilkinson AC, Nakauchi H. In vivo and ex vivo haematopoietic stem cell expansion. Curr Opin Hematol. 2020 Jul;27(4):273-278. doi: 10.1097/MOH.0000000000000593.
Wilkinson AC. Hope for hematological diseases. Science. 2020 Mar 13;367(6483):1206. doi: 10.1126/Science.aba6108.
Wilkinson AC, Ishida R, Nakauchi H, Yamazaki S. Long-term ex vivo expansion of mouse hematopoietic stem cells. Nat Protoc. 2020 Feb;15(2):628-648. doi: 10.1038/s41596-019-0263-2.
Nishimura T, Hsu I, Martinez-Krams DC, Nakauchi Y, Majeti R, Yamazaki S, Nakauchi H, Wilkinson AC. Use of polyvinyl alcohol for chimeric antigen receptor T-cell expansion. Exp Hematol. 2019 Dec;80:16-20. doi: 10.1016/j.exphem.2019.11.007.
Luis TC, Wilkinson AC, Beerman I, Jaiswal S, Shlush LI. Biological implications of clonal hematopoiesis. Exp Hematol.2019 Sep;77:1-5. doi: 10.1016/j.exphem.2019.08.004.
Wilkinson AC, Ryan DJ, Kucinski I, Wang W, Yang J, Nestorowa S, Diamanti E, Tsang JC, Wang J, Campos LS, Yang F, Fu B, Wilson N, Liu P, Gottgens B. Expanded potential stem cell media as a tool to study human developmental hematopoiesis in vitro. Exp Hematol. 2019 Aug;76:1-12.e5. doi: 10.1016/j.exphem.2019.07.003.
Wilkinson AC, Ishida R, Kikuchi M, Sudo K, Morita M, Crisostomo RV, Yamamoto R, Loh KM, Nakamura Y, Watanabe M, Nakauchi H, Yamazaki S. Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation. Nature. 2019 Jul;571(7763):117-121. doi: 10.1038/s41586-019-1244-x.
Yamamoto R, Wilkinson AC, Nakauchi H. Changing concepts in hematopoietic stem cells. Science. 2018 Nov 23;362(6417):895-896. doi: 10.1126/Science.aat7873.
Kauts ML, De Leo B, Rodríguez-Seoane C, Ronn R, Glykofrydis F, Maglitto A, Kaimakis P, Basi M, Taylor H, Forrester L, Wilkinson AC, Göttgens B, Saunders P, Dzierzak E. Rapid Mast Cell Generation from Gata2 Reporter Pluripotent Stem Cells. Stem Cell Reports. 2018 Oct 9;11(4):1009-1020. doi: 10.1016/j.stemcr.2018.08.007.
Wilkinson AC, Morita M, Nakauchi H, Yamazaki S. Branched-chain amino acid depletion conditions bone marrow for hematopoietic stem cell transplantation avoiding amino acid imbalance-associated toxicity. Exp Hematol. 2018 Jul;63:12-16.e1. doi: 10.1016/j.exphem.2018.04.004. Epub 2018 Apr 26.
Yamamoto R, Wilkinson AC, Ooehara J, Lan X, Lai CY, Nakauchi Y, Pritchard JK, Nakauchi H. Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment. Cell Stem Cell. 2018 Apr 5;22(4):600-607.e4. doi: 10.1016/j.stem.2018.03.013.
Wilkinson AC, Yamazaki S. The hematopoietic stem cell diet. Int J Hematol. 2018 Jun;107(6):634-641. doi: 10.1007/s12185-018-2451-1.
Ananieva EA, Wilkinson AC. Branched-chain amino acid metabolism in cancer. Curr Opin Clin Nutr Metab Care. 2018 Jan;21(1):64-70. doi: 10.1097/MCO.0000000000000430
Wilkinson AC, Nakauchi H, Göttgens B. Mammalian Transcription Factor Networks: Recent Advances in Interrogating Biological Complexity. Cell Syst. 2017 Oct 25;5(4):319-331. doi: 10.1016/j.cels.2017.07.004.
Yang J, Ryan DJ, Wang W, Tsang JC, Lan G, Masaki H, Gao X, Antunes L, Yu Y, Zhu Z, Wang J, Kolodziejczyk AA, Campos LS, Wang C, Yang F, Zhong Z, Fu B, Eckersley-Maslin MA, Woods M, Tanaka Y, Chen X, Wilkinson AC, Bussell J, White J, Ramirez-Solis R, Reik W, Göttgens B, Teichmann SA, Tam PPL, Nakauchi H, Zou X, Lu L, Liu P. Establishment of mouse expanded potential stem cells. Nature. 2017 Oct 19;550(7676):393-397. doi: 10.1038/nature24052.
Tsukada M, Ota Y, Wilkinson AC, Becker HJ, Osato M, Nakauchi H, Yamazaki S. In Vivo Generation of Engraftable Murine Hematopoietic Stem Cells by Gfi1b, c-Fos, and Gata2 Overexpression within Teratoma. Stem Cell Reports. 2017 Oct 10;9(4):1024-1033. doi: 10.1016/j.stemcr.2017.08.010.
Gundry MC, Dever DP, Yudovich D, Bauer DE, Haas S, Wilkinson AC, Singbrant S. Technical considerations for the use of CRISPR/Cas9 in hematology research. Exp Hematol. 2017 Oct;54:4-11. doi: 10.1016/j.exphem.2017.07.006.
Ieyasu A, Ishida R, Kimura T, Morita M, Wilkinson AC, Sudo K, Nishimura T, Ohehara J, Tajima Y, Lai CY, Otsu M, Nakamura Y, Ema H, Nakauchi H, Yamazaki S. An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors. Stem Cell Reports. 2017 Mar 14;8(3):500-508. doi: 10.1016/j.stemcr.2017.01.015.
Tajima Y, Ito K, Umino A, Wilkinson AC, Nakauchi H, Yamazaki S. Continuous cell supply from Krt7-expressing hematopoietic stem cells during native hematopoiesis revealed by targeted in vivo gene transfer method. Sci Rep. 2017 Jan 18;7:40684. doi: 10.1038/srep40684.
Taya Y, Ota Y, Wilkinson AC, Kanazawa A, Watarai H, Kasai M, Nakauchi H, Yamazaki S. Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation. Science. 2016 Dec 2;354(6316):1152-1155. doi: 10.1126/Science.aag3145.
Wilson NK, Schoenfelder S, Hannah R, Sánchez Castillo M, Schütte J, Ladopoulos V, Mitchelmore J, Goode DK, Calero-Nieto FJ, Moignard V, Wilkinson AC, Jimenez-Madrid I, Kinston S, Spivakov M, Fraser P, Göttgens B. Integrated genome-scale analysis of the transcriptional regulatory landscape in a blood stem/progenitor cell model. Blood. 2016 Mar 31;127(13):e12-23. doi: 10.1182/blood-2015-10-677393.
Watson JK, Rulands S, Wilkinson AC, Wuidart A, Ousset M, Van Keymeulen A, Göttgens B, Blanpain C, Simons BD, Rawlins EL. Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium. Cell Rep. 2015 Jul 7;12(1):90-101. doi: 10.1016/j.celrep.2015.06.011.
Moignard V, Woodhouse S, Haghverdi L, Lilly AJ, Tanaka Y, Wilkinson AC, Buettner F, Macaulay IC, Jawaid W, Diamanti E, Nishikawa SI, Piterman N, Kouskoff V, Theis FJ, Fisher J, Göttgens B. Decoding the regulatory network of early blood development from single-cell gene expression measurements. Nat Biotechnol. 2015 Mar;33(3):269-276. doi: 10.1038/nbt.3154.
Sánchez-Castillo M, Ruau D, Wilkinson AC, Ng FS, Hannah R, Diamanti E, Lombard P, Wilson NK, Gottgens B. CODEX: a next-generation sequencing experiment database for the haematopoietic and embryonic stem cell communities. Nucleic Acids Res. 2015 Jan;43(Database issue):D1117-23. doi: 10.1093/nar/gku895.
Wilkinson AC, Kawata VK, Schütte J, Gao X, Antoniou S, Baumann C, Woodhouse S, Hannah R, Tanaka Y, Swiers G, Moignard V, Fisher J, Hidetoshi S, Tijssen MR, de Bruijn MF, Liu P, Göttgens B. Single-cell analyses of regulatory network perturbations using enhancer-targeting TALEs suggest novel roles for PU.1 during haematopoietic specification. Development. 2014 Oct;141(20):4018-30. doi: 10.1242/dev.115709.
Wilkinson AC, Goode DK, Cheng YH, Dickel DE, Foster S, Sendall T, Tijssen MR, Sanchez MJ, Pennacchio LA, Kirkpatrick AM, Göttgens B. Single site-specific integration targeting coupled with embryonic stem cell differentiation provides a high-throughput alternative to in vivo enhancer analyses. Biol Open. 2013 Oct 7;2(11):1229-38. doi: 10.1242/bio.20136296.
Wilkinson AC, Göttgens B. Transcriptional regulation of haematopoietic stem cells. Adv Exp Med Biol. 2013;786:187-212. doi: 10.1007/978-94-007-6621-1_11.
Wilkinson AC, Ballabio E, Geng H, North P, Tapia M, Kerry J, Biswas D, Roeder RG, Allis CD, Melnick A, de Bruijn MF, Milne TA. RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. Cell Rep. 2013 Jan 31;3(1):116-27. doi: 10.1016/j.celrep.2012.12.016.
Gardner PP, Daub J, Tate JG, Nawrocki EP, Kolbe DL, Lindgreen S, Wilkinson AC, Finn RD, Griffiths-Jones S, Eddy SR, Bateman A. Rfam: updates to the RNA families database. Nucleic Acids Res. 2009 Jan;37(Database issue):D136-40. doi: 10.1093/nar/gkn766.
