Lu Group

Research Summary

Normally, we store our genetic information in 23 pairs of chromosomes. However, cancer cells seldom conform to this number. Rather, cancer cells undergo whole genome doubling to duplicate all their 23 pairs of chromosomes to 46 pairs in one fell swoop. Following this, mutations and chromosomal rearrangements occur repeatedly in cancer cells, resulting in a population of highly variable chromosomal numbers. These events correlate with worse clinical outcomes, drug resistance and cancer metastasis.

Using existing population genomic and clinical data, our lab aims to functionally characterise the events that contribute to whole genome doubling and chromosomal instability. We are interested in FAT protocadherins,  a class of proteins which are often mutated in lung, breast, skin and oesophageal cancers. By understanding the role played by the FAT proteins, we aim to find novel treatment strategies

See our research briefing article for a brief summary!

Selected Publications:

Lu WT*, Lykourgos-Panagiotis Z, ……., Swanton C*. Functional Characterisation of driver events from TRACERx reveals mechanisms of NSCLC evolution. Nature Cell Biology, 2025. *Co-correspondence. [link]

Bailey C, Pich O, Thol K, Watkins TBK, Luebeck J, …… Lu WT, ……, Swanton C. Origins and Impact of Extrachromosomal DNA. Nature, 2024. [link]

Dietzen M, Zhai H,Lucas O, Pich O, Barrington C, Lu WT, ……Swanton C, Kanu N, McGranahan N. Replication timing alteration impact mutation acquisition during tumor evolution in breast and lung cancer. Nature Communications, 2024.[link]

Bader AS, Luessing L, Hawley BR, Skalka GL, Lu WT, Lowndes NL, and Bushell M. DDX17 is required for efficient DSB repair at DNA: RNA hybrid deficient loci. Nucleic Acids Research, 2022.[link]

Venkatesan S, Angelova M, Puttick C, Zhai H, Caswell D, Lu WT, ……, Swanton C. Induction of APOBEC3 exacerbates DNA replication stress and chromosomal instability in breast and lung cancer evolution. Cancer Discovery, 2021.[link]

Lu WT*, Hawley BR*, Skalka GL, Baldock RA, Bader AS, Smith E, Malewicz M, Watts FZ, Wilczynska A, and Bushell M. Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA damage repair. Nature Communications 2018 *Co-first authorship. [link]

Hawley BR*, Lu WT*, Wilczynska A, and Bushell M. The emerging role of RNAs in DNA damage repair. Review. Cell Death and Differentiation 2017*Co-first authorship.[link]

Kamenska A, Lu WT, …..Bushell M and Standart N. Human 4E-T represses translation of bound mRNAs and enhances microRNA-mediated silencing. Nucleic Acids Research 2014 [link]

Meijer HA*, Kong YW *, Lu WT *, Wilczynska A*, Spriggs RV, Robinson SW, Godfrey JD, Willis AE, Bushell M. Translational Repression and eIF4A2 Activity are Critical for microRNA-Mediated Gene Regulation. Science 2013*Co-first authorship.[link]

Join US!!!

Are you:

🔥Passionate about genomic and chromosomal instability?
❓Curious about the relationship between whole genome doubling, cancer evolution & drug resistance?
🩺Want to have close collaboration with groups that deal with clinical data?

If so, contact us!

Team Members

Wei-Ting Lu - Group Leader

Tristan Kennedy - Postdoctoral Researcher

Soham De - MRes Student

Collaborators

Prof. Eileen Parkes, University of Oxford, UK

Prof. Nnennaya Kanu, University College London, UK

Prof. Fabrice André, Institut Gustave Roussy, France (SCANDARE cohort)

Prof.  Christophe Le Tourneau, Institut Curie, France (SCANDARE cohort)

Dr. Monica Arnedos, Bordeaux Institute of Oncology, France (SCANDARE cohort)

Prof. Sherene Loi, Peter MacCallum Cancer Centre,  Australia (kConFab cohort)

Dr Heather Thorne, Peter MacCallum Cancer Centre, Australia (kConFab cohort)