Louise van der Weyden, PhD | Senior Staff Scientist

van der Weyden, Louise

I’m fascinated by metastasis - both the genetic alterations that drive a cancer cell to acquire metastatic capabilities and the role of the microenvironment (immune cells, endothelial cells, stroma) in regulating this process.

Metastasis is responsible for approximately 90% of human cancer patient deaths. This multi-stage process requires tumour cells to survive in the circulation, extravasate at distant sites then proliferate, and involves contributions from both the tumour cell and the microenvironment. The early steps in this process are believed to be quite efficient, such that it is regulation of tumour cell growth after extravasation (known as ‘colonization’) that determines metastatic outcome.

We focus our studies on melanoma metastasis, as although melanoma accounts for only ~2% of skin cancer cases, it is responsible for the majority of skin cancer deaths. This is because melanoma has an incredible propensity to metastasize, and unlike other cancers, it frequently spreads to multiple organs. Once melanoma has spread to distant organs, the 5 year survival rate for the patient rate is very poor.

In 1889 Stephen Paget proposed the “seed and soil” hypothesis to explain the nature of metastasis. To understand the “seed” we’re sequencing primary melanomas and their metastatic counterparts (from both human patients and experimental animal models) to identify genes that confer metastatic capability to a cell, and that correlate with survival/outcome of the patient. To understand the “soil” we’re looking at the role of non-cell autonomous factors, such as the tumour microenvironment (including stromal cells, endothelial cells and the immune system) in regulating the ability of metastasis to occur. In particular we perform an 'experimental metastasis assay' on knockout mice coming through the Sanger Institute's Mouse Pipelines (http://www.mousephenotype.org/) to identify genes, that when disrupted in the mouse, modify the ability of the metastatic melanoma cells to effectively colonise the lung.

Understanding genes that are altered in metastasis or host/microenvironmental genes that can regulate metastasis will hopefully pave the way for identifying potential new drug targets.

Publications

  • Genome-wide in vivo screen identifies novel host regulators of metastatic colonization.

    van der Weyden L, Arends MJ, Campbell AD, Bald T, Wardle-Jones H et al.

    Nature 2017;541;7636;233-236

  • Genome wide in vivo mouse screen data from studies to assess host regulation of metastatic colonisation.

    van der Weyden L, Karp NA, Swiatkowska A, Adams DJ and Speak AO

    Scientific data 2017;4;170129

  • Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer.

    Ahmad I, Mui E, Galbraith L, Patel R, Tan EH et al.

    Proceedings of the National Academy of Sciences of the United States of America 2016;113;29;8290-5

  • Gray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice.

    Guerrero JA, Bennett C, van der Weyden L, McKinney H, Chin M et al.

    Blood 2014;124;24;3624-35

  • Genome wide in vivo mouse screen data from studies to assess host regulation of metastatic colonisation.

    van der Weyden L, Karp NA, Swiatkowska A, Adams DJ and Speak AO

    Scientific data 2017;4;170129

  • Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1.

    Rathjen T, Yan X, Kononenko NL, Ku MC, Song K et al.

    Nature neuroscience 2017

  • Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity.

    Thomas DC, Clare S, Sowerby JM, Pardo M, Juss JK et al.

    The Journal of experimental medicine 2017;214;4;1111-1128

  • Genome-wide in vivo screen identifies novel host regulators of metastatic colonization.

    van der Weyden L, Arends MJ, Campbell AD, Bald T, Wardle-Jones H et al.

    Nature 2017;541;7636;233-236

  • Analyzing tumor heterogeneity and driver genes in single myeloid leukemia cells with SBCapSeq.

    Mann KM, Newberg JY, Black MA, Jones DJ, Amaya-Manzanares F et al.

    Nature biotechnology 2016

  • Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer.

    Ahmad I, Mui E, Galbraith L, Patel R, Tan EH et al.

    Proceedings of the National Academy of Sciences of the United States of America 2016;113;29;8290-5

  • Alkaline ceramidase 1 is essential for mammalian skin homeostasis and regulating whole body energy expenditure.

    Liakath-Ali K, Vancollie VE, Lelliott CJ, Speak AO, Lafont D et al.

    The Journal of pathology 2016

  • Cross-species models of human melanoma.

    van der Weyden L, Patton EE, Wood GA, Foote AK, Brenn T et al.

    The Journal of pathology 2016;238;2;152-65

  • A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression.

    Giotopoulos G, van der Weyden L, Osaki H, Rust AG, Gallipoli P et al.

    The Journal of experimental medicine 2015;212;10;1551-69

  • Somatic drivers of B-ALL in a model of ETV6-RUNX1; Pax5(+/-) leukemia.

    van der Weyden L, Giotopoulos G, Wong K, Rust AG, Robles-Espinoza CD et al.

    BMC cancer 2015;15;585

  • PAX5 is a tumor suppressor in mouse mutagenesis models of acute lymphoblastic leukemia.

    Dang J, Wei L, de Ridder J, Su X, Rust AG et al.

    Blood 2015;125;23;3609-17

  • RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2.

    Pefani DE, Latusek R, Pires I, Grawenda AM, Yee KS et al.

    Nature cell biology 2015;17;4;531

  • Human T-cell leukemia virus type 1 (HTLV-1) tax requires CADM1/TSLC1 for inactivation of the NF-κB inhibitor A20 and constitutive NF-κB signaling.

    Pujari R, Hunte R, Thomas R, van der Weyden L, Rauch D et al.

    PLoS pathogens 2015;11;3;e1004721

  • Gray platelet syndrome: proinflammatory megakaryocytes and α-granule loss cause myelofibrosis and confer metastasis resistance in mice.

    Guerrero JA, Bennett C, van der Weyden L, McKinney H, Chin M et al.

    Blood 2014;124;24;3624-35

  • RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2.

    Pefani DE, Latusek R, Pires I, Grawenda AM, Yee KS et al.

    Nature cell biology 2014;16;10;962-71, 1-8

  • Cancer gene discovery goes mobile.

    van der Weyden L, Ranzani M and Adams DJ

    Nature genetics 2014;46;9;928-9

  • Insertional mutagenesis and deep profiling reveals gene hierarchies and a Myc/p53-dependent bottleneck in lymphomagenesis.

    Huser CA, Gilroy KL, de Ridder J, Kilbey A, Borland G et al.

    PLoS genetics 2014;10;2;e1004167

  • Cancer of mice and men: old twists and new tails.

    van der Weyden L and Adams DJ

    The Journal of pathology 2013;230;1;4-16

  • Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity.

    van der Weyden L, Rust AG, McIntyre RE, Robles-Espinoza CD, del Castillo Velasco-Herrera M et al.

    Oncogene 2013;32;3;397-402

  • Generation of the Sotos syndrome deletion in mice.

    Migdalska AM, van der Weyden L, Ismail O, Sanger Mouse Genetics Project, Rust AG et al.

    Mammalian genome : official journal of the International Mammalian Genome Society 2012;23;11-12;749-57

  • Using mice to unveil the genetics of cancer resistance.

    van der Weyden L and Adams DJ

    Biochimica et biophysica acta 2012;1826;2;312-30

  • Sequencing and characterization of the FVB/NJ mouse genome.

    Wong K, Bumpstead S, Van Der Weyden L, Reinholdt LG, Wilming LG et al.

    Genome biology 2012;13;8;R72

  • Loss of RASSF1A synergizes with deregulated RUNX2 signaling in tumorigenesis.

    van der Weyden L, Papaspyropoulos A, Poulogiannis G, Rust AG, Rashid M et al.

    Cancer research 2012;72;15;3817-3827

  • Nuclear receptor binding protein 1 regulates intestinal progenitor cell homeostasis and tumour formation.

    Wilson CH, Crombie C, van der Weyden L, Poulogiannis G, Rust AG et al.

    The EMBO journal 2012;31;11;2486-97

  • Increased tumorigenesis associated with loss of the tumor suppressor gene Cadm1.

    van der Weyden L, Arends MJ, Rust AG, Poulogiannis G, McIntyre RE and Adams DJ

    Molecular cancer 2012;11;29

  • The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma.

    Pérez-Mancera PA, Rust AG, van der Weyden L, Kristiansen G, Li A et al.

    Nature 2012;486;7402;266-70

  • Cancer gene discovery in the mouse.

    McIntyre RE, van der Weyden L and Adams DJ

    Current opinion in genetics & development 2012;22;1;14-20

  • Disruption of mouse Cenpj, a regulator of centriole biogenesis, phenocopies Seckel syndrome.

    McIntyre RE, Lakshminarasimhan Chavali P, Ismail O, Carragher DM, Sanchez-Andrade G et al.

    PLoS genetics 2012;8;11;e1003022

  • Modeling partial monosomy for human chromosome 21q11.2-q21.1 reveals haploinsufficient genes influencing behavior and fat deposition.

    Migdalska AM, van der Weyden L, Ismail O, White JK, Sanger Mouse Genetics Project et al.

    PloS one 2012;7;1;e29681

  • High-throughput semiquantitative analysis of insertional mutations in heterogeneous tumors.

    Koudijs MJ, Klijn C, van der Weyden L, Kool J, ten Hoeve J et al.

    Genome research 2011;21;12;2181-9

  • Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis.

    March HN, Rust AG, Wright NA, ten Hoeve J, de Ridder J et al.

    Nature genetics 2011;43;12;1202-9

  • Mouse genomic variation and its effect on phenotypes and gene regulation.

    Keane TM, Goodstadt L, Danecek P, White MA, Wong K et al.

    Nature 2011;477;7364;289-94

  • Computational identification of insertional mutagenesis targets for cancer gene discovery.

    de Jong J, de Ridder J, van der Weyden L, Sun N, van Uitert M et al.

    Nucleic acids research 2011;39;15;e105

  • Modeling the evolution of ETV6-RUNX1-induced B-cell precursor acute lymphoblastic leukemia in mice.

    van der Weyden L, Giotopoulos G, Rust AG, Matheson LS, van Delft FW et al.

    Blood 2011;118;4;1041-51

  • Acute sensitivity of the oral mucosa to oncogenic K-ras.

    van der Weyden L, Alcolea MP, Jones PH, Rust AG, Arends MJ and Adams DJ

    The Journal of pathology 2011;224;1;22-32

  • Cadm1 expression and function in the mouse lens.

    De Maria A, Shi Y, Luo X, Van Der Weyden L and Bassnett S

    Investigative ophthalmology & visual science 2011;52;5;2293-9

  • Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia.

    Crossan GP, van der Weyden L, Rosado IV, Langevin F, Gaillard PH et al.

    Nature genetics 2011;43;2;147-52

  • The mouse genetics toolkit: revealing function and mechanism.

    van der Weyden L, White JK, Adams DJ and Logan DW

    Genome biology 2011;12;6;224

  • Rec8-containing cohesin maintains bivalents without turnover during the growing phase of mouse oocytes.

    Tachibana-Konwalski K, Godwin J, van der Weyden L, Champion L, Kudo NR et al.

    Genes & development 2010;24;22;2505-16

  • Proapoptotic Rassf1A/Mst1 signaling in cardiac fibroblasts is protective against pressure overload in mice.

    Del Re DP, Matsuda T, Zhai P, Gao S, Clark GJ et al.

    The Journal of clinical investigation 2010;120;10;3555-67

  • Comment on "CRTAM confers late-stage activation of CD8+ T cells to regulate retention within lymph node".

    Wong SH, Vannberg FO, Spencer AJ, van der Weyden L, Hill AV and Wyllie DH

    Journal of immunology (Baltimore, Md. : 1950) 2010;184;8;4052-3

  • Ectodomains of the LDL receptor-related proteins LRP1b and LRP4 have anchorage independent functions in vivo.

    Dietrich MF, van der Weyden L, Prosser HM, Bradley A, Herz J and Adams DJ

    PloS one 2010;5;4;e9960

  • Novel candidate cancer genes identified by a large-scale cross-species comparative oncogenomics approach.

    Mattison J, Kool J, Uren AG, de Ridder J, Wessels L et al.

    Cancer research 2010;70;3;883-95

  • The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus.

    Brass AL, Huang IC, Benita Y, John SP, Krishnan MN et al.

    Cell 2009;139;7;1243-54

  • Cancer gene discovery in mouse and man.

    Mattison J, van der Weyden L, Hubbard T and Adams DJ

    Biochimica et biophysica acta 2009;1796;2;140-61

  • Megaoesophagus in Rassf1a-null mice.

    van der Weyden L, Happerfield L, Arends MJ and Adams DJ

    International journal of experimental pathology 2009;90;2;101-8

  • A high-throughput splinkerette-PCR method for the isolation and sequencing of retroviral insertion sites.

    Uren AG, Mikkers H, Kool J, van der Weyden L, Lund AH et al.

    Nature protocols 2009;4;5;789-98

  • Contemporary approaches for modifying the mouse genome.

    Adams DJ and van der Weyden L

    Physiological genomics 2008;34;3;225-38

  • Loss of Rassf1a cooperates with Apc(Min) to accelerate intestinal tumourigenesis.

    van der Weyden L, Arends MJ, Dovey OM, Harrison HL, Lefebvre G et al.

    Oncogene 2008;27;32;4503-8

  • The Ras-association domain family (RASSF) members and their role in human tumourigenesis.

    van der Weyden L and Adams DJ

    Biochimica et biophysica acta 2007;1776;1;58-85

  • Renin enhancer is critical for control of renin gene expression and cardiovascular function.

    Adams DJ, Head GA, Markus MA, Lovicu FJ, van der Weyden L et al.

    The Journal of biological chemistry 2006;281;42;31753-61

  • Functional knockout of the matrilin-3 gene causes premature chondrocyte maturation to hypertrophy and increases bone mineral density and osteoarthritis.

    van der Weyden L, Wei L, Luo J, Yang X, Birk DE et al.

    The American journal of pathology 2006;169;2;515-27

  • TranscriptSNPView: a genome-wide catalog of mouse coding variation.

    Cunningham F, Rios D, Griffiths M, Smith J, Ning Z et al.

    Nature genetics 2006;38;8;853

  • Geminin is essential to prevent endoreduplication and to form pluripotent cells during mammalian development.

    Gonzalez MA, Tachibana KE, Adams DJ, van der Weyden L, Hemberger M et al.

    Genes & development 2006;20;14;1880-4

  • Loss of TSLC1 causes male infertility due to a defect at the spermatid stage of spermatogenesis.

    van der Weyden L, Arends MJ, Chausiaux OE, Ellis PJ, Lange UC et al.

    Molecular and cellular biology 2006;26;9;3595-609

  • A genome-wide, end-sequenced 129Sv BAC library resource for targeting vector construction.

    Adams DJ, Quail MA, Cox T, van der Weyden L, Gorick BD et al.

    Genomics 2005;86;6;753-8

  • The RASSF1A isoform of RASSF1 promotes microtubule stability and suppresses tumorigenesis.

    van der Weyden L, Tachibana KK, Gonzalez MA, Adams DJ, Ng BL et al.

    Molecular and cellular biology 2005;25;18;8356-67

  • Null and conditional semaphorin 3B alleles using a flexible puroDeltatk loxP/FRT vector.

    van der Weyden L, Adams DJ, Harris LW, Tannahill D, Arends MJ and Bradley A

    Genesis (New York, N.Y. : 2000) 2005;41;4;171-8

  • BRCTx is a novel, highly conserved RAD18-interacting protein.

    Adams DJ, van der Weyden L, Gergely FV, Arends MJ, Ng BL et al.

    Molecular and cellular biology 2005;25;2;779-88

  • cAMP controls human renin mRNA stability via specific RNA-binding proteins.

    Morris BJ, Adams DJ, Beveridge DJ, van der Weyden L, Mangs H and Leedman PJ

    Acta physiologica Scandinavica 2004;181;4;369-73

  • Mutagenic insertion and chromosome engineering resource (MICER).

    Adams DJ, Biggs PJ, Cox T, Davies R, van der Weyden L et al.

    Nature genetics 2004;36;8;867-71

  • HADHB, HuR, and CP1 bind to the distal 3'-untranslated region of human renin mRNA and differentially modulate renin expression.

    Adams DJ, Beveridge DJ, van der Weyden L, Mangs H, Leedman PJ and Morris BJ

    The Journal of biological chemistry 2003;278;45;44894-903

  • The structure of the zinc finger domain from human splicing factor ZNF265 fold.

    Plambeck CA, Kwan AH, Adams DJ, Westman BJ, van der Weyden L et al.

    The Journal of biological chemistry 2003;278;25;22805-11

  • Tools for targeted manipulation of the mouse genome.

    van der Weyden L, Adams DJ and Bradley A

    Physiological genomics 2002;11;3;133-64

  • Cancer: stuck at first base.

    van der Weyden L, Jonkers J and Bradley A

    Nature 2002;419;6903;127-8

  • Renin gene expression: the switch and the fingers.

    Morris BJ, Adams DJ and van der Weyden L

    Clinical and experimental pharmacology & physiology 2001;28;12;1044-7

  • ZNF265--a novel spliceosomal protein able to induce alternative splicing.

    Adams DJ, van der Weyden L, Mayeda A, Stamm S, Morris BJ and Rasko JE

    The Journal of cell biology 2001;154;1;25-32

  • Are we creating problems? Negative effects of Cre recombinase.

    Adams DJ and van der Weyden L

    Genesis (New York, N.Y. : 2000) 2001;29;3;115

  • Amino acid sequence of a neurotoxic phospholipase A2 enzyme from common death adder (Acanthophis antracticus) venom.

    van der Weyden L, Hains P, Broady K, Shaw D and Milburn P

    Journal of natural toxins 2001;10;1;33-42

  • Characterisation of the biochemical and biological variations from the venom of the death adder species (Acanthophis antarcticus, A. praelongus and A. pyrrhus).

    van der Weyden L, Hains PG and Broady KW

    Toxicon : official journal of the International Society on Toxinology 2000;38;12;1703-13

  • Extracellular ATP-dependent suppression of proliferation and induction of differentiation of human HL-60 leukemia cells by distinct mechanisms.

    Conigrave AD, van der Weyden L, Holt L, Jiang L, Wilson P et al.

    Biochemical pharmacology 2000;60;11;1585-91

  • Capacity for purinergic control of renin promoter via P2Y(11) receptor and cAMP pathways.

    van Der Weyden L, Adams DJ and Morris BJ

    Hypertension 2000;36;6;1093-8

  • Extracellular ATP couples to cAMP generation and granulocytic differentiation in human NB4 promyelocytic leukaemia cells.

    van der Weyden L, Rakyan V, Luttrell BM, Morris MB and Conigrave AD

    Immunology and cell biology 2000;78;5;467-73

  • Pharmacological characterisation of the P2Y11 receptor in stably transfected haematological cell lines.

    van der Weyden L, Adams DJ, Luttrell BM, Conigrave AD and Morris MB

    Molecular and cellular biochemistry 2000;213;1-2;75-81

  • Signal transduction and white cell maturation via extracellular ATP and the P2Y11 receptor.

    van der Weyden L, Conigrave AD and Morris MB

    Immunology and cell biology 2000;78;4;369-74

  • Pharmacological profile of a novel cyclic AMP-linked P2 receptor on undifferentiated HL-60 leukemia cells.

    Conigrave AD, Lee JY, van der Weyden L, Jiang L, Ward P et al.

    British journal of pharmacology 1998;124;7;1580-5

  • Acanthoxin, a toxic phospholipase A2 from the venom of the common death adder (Acanthophis antarcticus).

    van der Weyden L, Hains P, Morris M and Broady K

    Toxicon : official journal of the International Society on Toxinology 1997;35;8;1315-25

van der Weyden, Louise
Louise's Timeline
2017

University of Technology (UTS) Alumni Award for Excellence 2017 - Faculty of Science

2014

William Guy Forbeck Research Foundation (WGFRF) Scholar

2012

Senior Staff Scientist (Adams Lab, WTSI)

2007

Kay Kendall Leukaemia Foundation Intermediate Fellowship

2006

Post-doctoral fellow (Adams Lab, WTSI)

2002

NHMRC (Australia) CJ Martin & RG Menzies Fellowship

2001

Post-doctoral fellow (Bradley Lab, WTSI)

PhD, University of Sydney (Australia)

1997

BSc (Hons), University of Technology, Sydney (Australia) [Winner of the University Medal for the Faculty of Science, 1997]