Selected recent publications

Gene-Expression Profiling to Decipher Breast Cancer Inter-and Intratumor Heterogeneity

Swarbrick A*., Fernandez-Martinez A., Perou C.M.

*Corresponding author

Cold Spring Harbor Perspectives in Medicine,  2024

High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes.

Singh, M., Al-Eryani, G., Carswell, S., Ferguson, J.M., Blackburn, J., Barton, K., Roden, D., Luciani, F., Giang Phan, T., Junankar, S., Jackson, K., Goodnow, C.C., Smith, M.A., Swarbrick, A

Nature Communications, 2019

We solved a technical challenge of how to affordably and rapidly profile gene expression in tandem with full-length single molecule mRNA sequencing from thousands of cells. We developed this method to permit deep profiling of lymphocyte gene expression and receptor expression. We use it to show clonal expansion and trafficking of lymphocytes from the lymph node to tumour, and unique gene expression features of clonal populations. We are now extending this method to enable very deep cellular characterisation of molecular features such as splicing, recombination, mutations and gene fusions in cancer cell populations.

DNA barcoding reveals ongoing immunoediting of clonal cancer populations during metastatic progression and immunotherapy response

Baldwin L.A., Bartonicek N., Yang J., Wu S.Z., Deng N., Roden D.L., Chan C.-L., Al-Eryani G., Zanker D.J., Parker B.S., Swarbrick A., Junankar S.

Nature Communications,  2022

This paper shows that clonal diversity within cancers can contribute to immune evasion, during metastatic progression and during the response to immune checkpoint inhibitors

Deep whole genome sequencing identifies recurrent genomic alterations in commonly used breast cancer cell lines and patient-derived xenograft models

Deng N., Minoche A., Harvey K., Li M., Winkler J., Goga A., Swarbrick A.

Breast Cancer Research,  2022

Spatial maps of genetically diverse breast cancer cells

Al-Eryani G., Swarbrick A.

Nature,  2022

Mapping the cancer cell states conserved across solid tumors

Roden D., Swarbrick A.

Nature Genetics,  2022

A single-cell and spatially resolved atlas of human breast cancers

Wu S.Z., Al-Eryani G., Roden D.L., Junankar S., Harvey K., Andersson A., Thennavan A., Wang C., Torpy J.R., Bartonicek N., Wang T., Larsson L., Kaczorowski D., Weisenfeld N.I., Uytingco C.R., Chew J.G., Bent Z.W., Chan C.-L., Gnanasambandapillai V., Dutertre C.-A., Gluch L., Hui M.N., Beith J., Parker A., Robbins E., Segara D., Cooper C., Mak C., Chan B., Warrier S., Ginhoux F., Millar E., Powell J.E., Williams S.R., Liu X.S., O’Toole S., Lim E., Lundeberg J., Perou C.M., Swarbrick A.

Nature Genetics,  2021

This study maps the cellular landscape of primary breast cancers, focussing primarily on cellular states. We define a detailed cellular taxonomy of up to 52 states across epithelial, stromal & immune cells & develop a new single-cell classifier of intrinsic subtype, ‘scSubtyper’ (provisional patent application filed). Using spatial transcriptomics we map these cells into cellular communities, revealing the important spatial relationships between certain subsets of stromal cells & lymphocytes, which we are now pursuing as therapeutic targets. Finally, we reveal that breast cancers can be stratified into clinically-meaningful groups based on their cellular composition, a concept we coin ‘ecotypes’ (provisional patent application filed). This is a landmark paper in breast cancer research.

Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer.

Cazet, A.S., Hui, M.N., Elsworth, B.L., Wu, S.Z., Roden, D., Chan, C.L., Skhinas, J.N., Collot, R., Yang, J., Harvey, K., Johan, M.Z., Cooper, C., Nair, R., Herrmann, D., McFarland, A., Deng, N., Ruiz-Borrego, M., Rojo, F., Trigo, J.M., Bezares, S., Caballero, R., Lim, E., Timpson, P., O'Toole, S., Watkins, D.N., Cox, T.R., Samuel, M.S., Martin, M., Swarbrick, A

This manuscript is a key demonstration of the influence of the tumour microenvironment in driving cancer cell plasticity during drug treatment. Fundamental discoveries and preclinical modeling by my lab drove the development of a Phase I trial of an anti-neoplastic (docetaxel) + an anti-stromal (smoothened/hedgehog inhibitor) combination therapy for metastatic TNBC, in which 3/11 women experienced clinical benefit, including one complete response. While small patient numbers, this is early evidence for clinical response to a stromal-directed therapy. Larger clinical trials are in development.

miR-99b-5p, miR-380-3p, and miR-485-3p are novel chemosensitizing miRNAs in high-risk neuroblastoma

Holliday H., Yang J., Dodson E., Nikolic I., Kamili A., Wheatley M., Deng N., Alexandrou S., Davis T.P., Kavallaris M., Caldon C.E., McCarroll J., De Preter K., Mestdagh P., Marshall G.M., Simpson K.J., Fletcher J., Swarbrick A.

Molecular Therapy,  2022

Spatial deconvolution of HER2-positive breast cancer delineates tumor-associated cell type interactions

Andersson A., Larsson L., Stenbeck L., Salmén F., Ehinger A., Wu S.Z., Al-Eryani G., Roden D., Swarbrick A., Borg Å., Frisén J., Engblom C., Lundeberg J.

Nature Communications,  2021

Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models

Chew N.J., Lim Kam Sian T.C.C., Nguyen E.V., Shin S.-Y., Yang J., Hui M.N., Deng N., McLean C.A., Welm A.L., Lim E., Gregory P., Nottle T., Lang T., Vereker M., Richardson G., Kerr G., Micati D., Jardé T., Abud H.E., Lee R.S., Swarbrick A., Daly R.J.

Breast Cancer Research,  2021

Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis

Wu S.Z., Roden D.L., Al-Eryani G., Bartonicek N., Harvey K., Cazet A.S., Chan C.-L., Junankar S., Hui M.N., Millar E.A., Beretov J., Horvath L., Joshua A.M., Stricker P., Wilmott J.S., Quek C., Long G.V., Scolyer R.A., Yeung B.Z., Segara D., Mak C., Warrier S., Powell J.E., O’Toole S., Lim E., Swarbrick A.

Genome Medicine,  2021

Best practices for spatial profiling for breast cancer research with the GeoMx® digital spatial profiler

Bergholtz H., Carter J.M., Cesano A., Cheang M.C.U., Church S.E., Divakar P., Fuhrman C.A., Goel S., Gong J., Guerriero J.L., Hoang M.L., Hwang E.S., Kuasne H., Lee J., Liang Y., Mittendorf E.A., Perez J., Prat A., Pusztai L., Reeves J.W., Riazalhosseini Y., Richer J.K., Sahin Ö., Sato H., Schlam I., Sørlie T., Stover D.G., Swain S.M., Swarbrick A., Thompson E.A., Tolaney S.M., Warren S.E., GeoMx Breast Cancer Consortium

Cancers,  2021

Single-cell advances in stromal-leukocyte interactions in cancer

Wu S.Z., Swarbrick A.

Immunological Reviews,  2021

Inhibitor of Differentiation 4 (ID4) represses mammary myoepithelial differentiation via inhibition of HEB

Holliday H., Roden D., Junankar S., Wu S.Z., Baker L.A., Krisp C., Chan C.-L., McFarland A., Skhinas J.N., Cox T.R., Pal B., Huntington N.D., Ormandy C.J., Carroll J.S., Visvader J., Molloy M.P., Swarbrick A.

iScience,  2021

The androgen receptor is a tumor suppressor in estrogen receptor–positive breast cancer

Hickey T.E., Selth L.A., Chia K.M., Laven-Law G., Milioli H.H., Roden D., Jindal S., Hui M., Finlay-Schultz J., Ebrahimie E., Birrell S.N., Stelloo S., Iggo R., Alexandrou S., Caldon C.E., Abdel-Fatah T.M., Ellis I.O., Zwart W., Palmieri C., Sartorius C.A., Swarbrick A., Lim E., Carroll J.S., Tilley W.D.

Nature Medicine,  2021

This paradigm-changing paper showed that the Androgen Receptor is a tumour suppressor in ER+ BrCa (~ 70% of BrCa). Androgen agonists provide a powerful new tool in the therapeutic armoury. Fundamentally changes our understanding of breast cancer biology

This work was used to design a successful Phase 2 (NCT02463032) which led to fast-track designation from the FDA( https://bit.ly/3tffYLY) for androgens in ER+ metastatic breast cancer. A Phase 3 (NCT04869943) clinical trial also followed and is underway.

This work was accompanied by a commentary in the same issue of Nature Medicine.

- Caswell-Jin JL et al “Androgen receptor agonists as breast cancer therapeutics” Nature Medicine 2021

A MXI1-NUTM1 fusion protein with MYC-like activity suggests a novel oncogenic mechanism in a subset of NUTM1-rearranged tumors

McEvoy C.R., Holliday H., Thio N., Mitchell C., Choong D.Y., Yellapu B., Leong H.S., Xu H., Lade S., Browning J., Takano E.A., Byrne D.J., Gill A.J., Duong C.P., Li J., Fellowes A.P., Fox S.B., Swarbrick A., Prall O.W.J.

Laboratory Investigation,  2021

Stromal cell diversity associated with immune evasion in human triple-negative breast cancer

Wu S.Z., Roden D.L., Wang C., Holliday H., Harvey K., Cazet A.S., Murphy K.J., Pereira B., Al-Eryani G., Bartonicek N., Hou R., Torpy J.R., Junankar S., Chan C.-L., Lam C.E., Hui M.N., Gluch L., Beith J., Parker A., Robbins E., Segara D., Mak C., Cooper C., Warrier S., Forrest A., Powell J., O'Toole S., Cox T.R., Timpson P., Lim E., Liu X.S., Swarbrick A.

EMBO Journal,  2020

Featured on the journal cover and in a news and views article by Kalluri et al “A map of human breast cancer: new players in stromal-immune crosstalk” EMBO J 2020.

This was the first study to report a comprehensive cellular profile of triple negative breast cancer, a particularly poor-prognosis subset. We discovered novel subsets of stromal cells and inferred a role for them in suppressing anti-tumor immunity. 

Proteogenomic analysis of Inhibitor of Differentiation 4 (ID4) in basal-like breast cancer

Baker L.A., Baker L.A., Holliday H., Holliday H., Roden D., Roden D., Krisp C., Krisp C., Wu S.Z., Junankar S., Junankar S., Serandour A.A., Mohammed H., Nair R., Sankaranarayanan G., Law A.M.K., Law A.M.K., McFarland A., Simpson P.T., Lakhani S., Dodson E., Dodson E., Selinger C., Anderson L., Anderson L., Samimi G., Hacker N.F., Lim E., Ormandy C.J., Ormandy C.J., Naylor M.J., Simpson K., Nikolic I., O'Toole S., O'Toole S., O'Toole S., O'Toole S., Kaplan W., Cowley M.J., Carroll J.S., Molloy M., Swarbrick A.

Breast Cancer Research,  2020