I am a cell biologist and experimental haematologist who uses murine models and cell lines to study cancer development, genetic interactions and molecular responses. My gene of interest is RECQL4, which encodes a DNA helicase with essential functions in DNA replication and repair, and which causes Rothmund Thomson Syndrome (RTS) when mutated.

Using a wide variety of techniques, I investigate how pathogenic mutations affect RECQL4 function in order to identify ways to prevent and treat the symptoms and cancers associated with RTS.

Selected publications

Smeets MF, DeLuca E, Wall M, Quach JM, Chalk AM, Deans AJ, Heierhorst J, Purton LE, Izon DJ, Walkley CR. The Rothmund-Thomson syndrome helicase RECQL4 is essential for hematopoiesis. J Clin Invest. 2014 Aug;124(8):3551-65. doi: 10.1172/JCI75334. Epub 2014 Jun 24.

Smeets MF, Tan SY, Xu JJ, Anande G, Unnikrishnan A, Chalk AM, Taylor SR, Pimanda JE, Wall M, Purton LE, Walkley CR. Srsf2(P95H) initiates myeloid bias and myelodysplastic/myeloproliferative syndrome from hemopoietic stem cells. Blood. 2018 Aug 9;132(6):608-621. doi: 10.1182/blood-2018-04-845602. Epub 2018 Jun 14.

Castillo-Tandazo W, Smeets MF, Murphy V, Liu R, Hodson C, Heierhorst J, Deans AJ, Walkley CR. ATP-dependent helicase activity is dispensable for the physiological functions of Recql4. PLoS Genet. 2019 Jul 5;15(7):e1008266. doi: 10.1371/journal.pgen.1008266. eCollection 2019 Jul.

Castillo-Tandazo W, Frazier AE, Sims NA, Smeets MF, Walkley CR. Rothmund-Thomson Syndrome-like RECQL4 truncating mutations cause a haploinsufficient low bone mass phenotype in mice. Mol Cell Biol. 2020 Dec 23;41(3):e00590-20. doi: 10.1128/MCB.00590-20.

Xu JJ, Chalk AM, Nikolic I, Simpson KJ, Smeets MF, Walkley CR. Genome-wide screening identifies cell-cycle control as a synthetic lethal pathway with SRSF2P95H mutation. Blood Adv. 2022 Apr 12;6(7):2092-2106. doi: 10.1182/bloodadvances.2021004571.

Xu JJ, Chalk AM, Wall M, Langdon WY, Smeets MF, Walkley CR. Srsf2(P95H/+) co-operates with loss of TET2 to promote myeloid bias and initiate a chronic myelomonocytic leukemia-like disease in mice. Leukemia. 2022 Oct 21. doi: 10.1038/s41375-022-01727-6.

ORCID profile: 0000-0001-6027-4108

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