Dr David Gallego-Ortega

Group Leader - Tumour Development

Senior Research Officer

Conjoint/Adjunct Role(s)

Conjoint Lecturer, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney

           David completed his PhD in Biochemistry and Molecular Biology in 2008 at the Spanish National Research Council (CSIC), the largest research organization in Spain. After one year as Postdoctoral Scientist at Translational Cancer Drugs Pharma, a biotechnology company focused in oncology; he joined Professor Ormandy’s lab at the Garvan Institute of Medical Research in 2009 to work in mouse models of mammary gland development and breast cancer.  David has held a National Breast Cancer and Cure Cancer Australia Foundation Fellowship (2012 - 2015) and he currently holds a Cancer Institute New South Wales Career Development Fellowship (2017-2019).

           David's group studies mechanisms of tumour tolerance and progression driven by tumour infiltrated myeloid cell populations, with the overarching aim of identifying novel molecular targets for the development of immunotherapies. Our work demonstrates that targeting Myeloid Derived Suppressor Cells (MDSC) restores immune-system control over disease progression, offering novel therapeutic opportunities for breast cancer.

            Transcriptome analysis has been extensively used to understand heterogeneity of breast cancer and to predict response to therapy and patient outcome. Traditional gene expression profiling of bulk complex cell populations is often dominated by the major compartment, thus masking low-abundant populations and denying cellular diversity. We use massively-parallel single-cell transcriptomic technologies (scRNA-seq) to characterise breast tumour cell diversity, simultaneously analysing cancer cell heterogeneity and tumour-associated stromal cells, with a particular focus in the infiltrating immune system.

            Integration of scRNAseq technologies provides high-resolution molecular phenotyping of breast cancer, allowing us to accurately map regulatory networks of tumour development. Understanding the molecular mechanisms of the cancer-to-immune cell communication is essential for the development of immunotherapies. 

Research Interests

Single-cell transcriptomics
Mammary gland development
Mammary gland hierarchy / Stem and progenitor cells / Cell fate specification/ Linage tracing
Breast cancer
Basal breast cancer / Endocrine therapy resistance
Animal models of breast cancer
Tumour progression / Mechanisms of metastasis
Immunobiology of breast cancer

Awards and Honours

2016-2019 - Career Development Fellowship, Cancer Institute New South Wales.
2015 - NSW Office of Medical Research postdoctoral Award for Excellence in Medical Research. Australian Society of Medical Research (ASMR).
2014 - Heliflite Young Explorer Award for an Outstanding Early Career Researcher
2012-2016 - National Breast Cancer Foundation and Cure Cancer Australia Foundation Postdoctoral Fellowship
2012 - NSW Office of Medical Research postdoctoral Award for Excellence in Medical Research. Australian Society of Medical Research (ASMR).
2008 - Special Award for Outstanding Communication. 13th World Congress in Advances in Oncology. (Greece)
2008 - Travel Bursary Award. 20th Meeting of the European Association for Cancer Research (EACR) (France)
2004-2008 - FPI Scholarship. Education Ministry of Madrid, Spanish Government

Education

2008 - PhD (Biochemistry and Molecular Biology) Auntonomous University of Madrid - Spain
2001 - BSc (Genetics) Complutense University of Madrid - Spain

Selected Publications

F. Valdes-Mora, WJ. Locke, E. Bandres, D. Gallego-Ortega, P. Cejas, MA. Garcia-Cabezas, Y. Colino-Sanguino, J. Feliu, T. Gomez del Pulgar and JC. Lacal. Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer. Oncotarget 2017, in press.

AMK Law, E Lim, CJ Ormandyand #D Gallego-Ortega. The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy. Endocr Relat Cancer. 2017 Feb 13. pii: ERC-16-0404. doi: 10.1530/ERC-16-0404.  (# Corresponding author)

C Vennin, VT Chin, SC Warren, MC Lucas, D Herrmann, A Magenau,P Melenec, SN Walters, G Monte-Nieto, JRW Conway, M Nobis, AH Allam, RA McCloy, N Currey, M Pinese, A Boulghourjian, A Zaratzian, ASA Adam, C Heu, AM Nagrial, A Chou, A Steinmann, A Drury, D Froio, M Giry-Laterriere, NLE Harris, T Phan, R Jain, W Weninger, EJ McGhee, R Whan, AL Johns, JS Samra, L Chantrill, AJ Gill, M Kohonen-Corish, RP Harvey, AV Biankin, APGI, TRJ Evans, KI Anderson, ST Grey, CJ Ormandy, D Gallego-Ortega, Y Wang, MS Samuel, OJ Sansom, A Burgess, TR Cox, JP Morton, M Pajic and P Timpson.Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy and the onset of the metastatic niche. Science Translational Medicine 2017. 9(384). doi: 10.1126/scitranslmed.aai8504.

AIJ Young, AMK Law, L Castillo, S Chong, HD Cullen, M Koehler, S Herzog, T Brummer, EF Lee, WD Fairlie, MC Lucas, D Herrmann, A Allam, P Timpson, DN Watkins, EKA Millar, SA O’Toole, D Gallego-Ortega, CJ Ormandy and SR Oakes MCL-1 inhibition provides a new way to suppress breast cancer metastasis and increase sensitivity to dasatinib. Breast Cancer Research 2016.

CL Piggin, DL Roden, D Gallego-Ortega, HJ Lee, SR Oakes and CJ Ormandy. ELF5 isoform expression is tissue-specific and significantly altered in cancerBreast Cancer Res 2016, Jan 7;18(1):4. doi: 10.1186/s13058-015-0666-0.

#D Gallego-Ortega, A Ledger, DL Roden, AMK Law, A Magenau, Z Kikhtyak, C Cho, SL Allerdice, HJ Lee, F Valdes-Mora, D Herrmann, R Salomon, AIJ Young, BY Lee, CM Sergio, W Kaplan, C Piggin, JRW Conway, B Rabinovich, EKA Millar, SR Oakes, T Chtanova, A Swarbrick, MJ Naylor, S O’Toole, AR Green, P Timpson, JMW Gee, IO Ellis, SJ Clark and #CJ Ormandy. ELF5 drives lung metastasis in luminal breast cancer through recruitment of Gr1+ CD11b+ myeloid-derived suppressor cellsPLoS Biol. 2015 Dec 30;13(12):e1002330. (# corresponding author).

Z Erami, D Herrmann, M Nobis, EJ McGhee, W Leung, N Reischmann, A Mrowinska, JP Schwarz, S Kadir, JRW Conway, SA Karim, C Steele, D Morran, D Gallego-Ortega, A Magenau, RA Ridgway, AKM Law, SN Walters, ST Grey, L Zhang, H Herzog, EC Hardeman, PW Gunning, CJ Ormandy, TRJ Evans, D Strathdee, OJ Sansom, JP Morton, KI Anderson and P Timpson. Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease and drug-dependent dynamic regulation of cell-cell junctions in live tissue. Cell Rep. 2015 Dec 22. pii: S2211-1247(15)01433-3

Junankar S, *Baker LA, *Roden DL, Nair R, Elsworth B, Gallego-Ortega D, Lacaze P, Cazet A, Nikolic I, Teo WS, Yang J, McFarland A, Harvey K, Naylor MJ, Lakhani SR, Simpson PT, Raghavendra A, Saunus J, Madore J, Kaplan W, Ormandy C, Millar EK, O'Toole S, Yun K, Swarbrick A. ID4 controls mammary stem cells and marks breast cancers with a stem cell-like phenotype. Nat Commun. 2015 Mar 27;6:6548. (* Contributed equally)

*Oakes SR., *Gallego-Ortega D. and Ormandy CJ. The mammary cellular hierarchy and breast cancer. Cell Mol Life Sci. 2014 Nov;71(22):4301-24. (* Contributed equally)

D. Gallego-Ortega, SR. Oakes, HJ. Lee, CL. Piggin, CJ. Ormandy. ELF5, normal mammary development and the heterogeneous phenotypes of breast cancer. Breast Cancer Management, 2013; 2(6): 489-498.

A. Stone, MJ. Cowley, F. Valdes-Mora, RA. McCloy, CM. Sergio, D. Gallego-Ortega, CE Caldon, CJ. Ormandy, AV. Biankin, JMW Gee, RI. Nicholson, CG. Print, SJ. Clark, RL. Sutherland and EA. Musgrove. BCL-2 hypermethylation is a potential biomarker of sensitivity to anti-mitotic chemotherapy in endocrine-resistant breast cancer. Molecular Cancer Therapeutics, 2013; 12(9):1874-85.

HJ. Lee, D. Gallego-Ortega, A. Ledger, D. Schramek, P. Joshi, MM. Swarc, C. Cho, JP. Lydon, R. Khokha, JM. Penninger, and CJ. Ormandy. Progesterone drives mammary secretory differentiation via RankL-induction of Elf5 in luminal progenitor cells. Development, 2013; 140(7):1397-401.

DR. Croucher, F. Hochgräfe, L. Zhang, L. Liu, RJ. Lyons, D. Rickwood, CM. Tactacan, BC. Browne, N. Ali, H. Chan, RF. Shearer, D. Gallego-Ortega, DN. Saunders, A. Swarbrick and R. Daly. A novel signaling pathway in basal breast cancer involving Lyn and the atypical kinase SgK269/PEAK1. Cancer Res. 2013; 73(6):1969-80. 

*M. Kalyuga - *D. Gallego-Ortega, H. Lee, M. Cowley, CE. Caldon, A. Stone, S. Allerdice, F. Valdes-Mora, R. Launchbury, A. Statham, N. Armstrong, C. Alles, A. Young, A. Egger, W. Au, C. Piggin, C. Evans, T. Brummer, W. Kaplan, JMW. Gee, RI. Nicholson, RL. Sutherland, A. Swarbrick, MJ. Naylor, S. Clark, J. Carroll and CJ. Ormandy. ELF5 transcriptionally specifies basal from luminal breast cancer and underpins the acquisition of antiestrogen resistance. PLoS Biol. 2012; 10(12):e1001461. (* Joint first authors).

C. Ortiz Padilla, D. Gallego-Ortega, BC. Browne, F. Hochgräfe, CE. Caldon, RJ. Lyons, DR. Croucher, D. Rickwood, CJ. Ormandy, T. Brummer and RJ. Daly. Functional characterization of cancer-associated Gab1 mutation. Oncogene 2012; doi: 10.1038/onc.2012.271.

HJ. Lee* - RA. Hinshelwood*, T. Bouras, D. Gallego-Ortega, F. Valdes-Mora, JE. Visvader, SJ Clark^ and CJ. Ormandy^. Lineage Specific Methylation of the Elf5 Promoter in Mammary Epithelial Cells. Stem Cells 2011; 29(10):1611-9. (*^ Contributed equally)

M.I. Cerezo-Guisado, P. del Reino, G. Remy, Y. Kuma, JS. Arthur, D. Gallego-Ortega and A. Cuenda. Evidence of p38g and p38d involvement in cell transformation processes. Carcinogenesis, 2011; 32(7):1093-9.

*Gallego-Ortega D. - *Gómez del Pulgar MT., Valdés-Mora F.,  Cebrián A, and Lacal JC. Involvement of human choline kinase alpha and beta in carcinogenesis: a differential role in lipid metabolism and biological functions. Review. Adv Enzyme Regul. 2011; 51(1):183-94. (* Joint first authors).

*BT. Chua - *D. Gallego-Ortega, A. Ramirez de Molina, A. Ullrich, JC. Lacal, J. Downward. Regulation of AKT(ser473) phosphorylation by choline kinase in breast carcinoma cells. Mol Cancer, 2009; 8:131. (* Joint first authors).

D. Gallego-Ortega, A. Ramirez de Molina, MA. Ramos, F. Valdés-Mora, MG. Barderas, J. Sarmentero-Estrada and JC Lacal. Differential role of choline kinase alpha and beta isoforms in human carcinogenesis. PLoS One, 2009;  4(11):e7819.

F. Valdés-Mora, T. Gómez del Pulgar, E. Bandrés, P. Cejas, A. Ramírez de Molina, R. Pérez-Palacios, D. Gallego-Ortega, MA. García-Cabezas, M. Nistal, M. González-Barón, J. García-Foncillas and JC. Lacal. The transcription factor TWIST1 is a prognostic factor in human colon cancer. Ann Surg Oncol. 2009; 16(1):78-87. Epub 2008. Nov 11.

Ramírez de Molina A, Gallego-Ortega D, Sarmentero-Estrada J, Lagares D, Gómez del Pulgar T, Bandrés E, García-Foncillas J and Lacal JC. Choline kinase as a link connecting phospholipid metabolism and cell cycle regulation: implications in cancer therapy. Int. J. Biochem Cell Biol 2008; Jan 19.

Ramirez de Molina A, Sarmentero-Estrada J, Belda-Iniesta C, Taron M, de Molina VR, Cejas P, Skrzypski M, Gallego-Ortega D, de Castro J, Casado E, Garcia-Cabezas MA, Sanchez JJ, Nistal M, Rosell R, Gonzalez-Baron M, Lacal JC. Expression of choline kinase alpha to predict outcome in patients with early-stage non-small-cell lung cancer: a retrospective study. Lancet Oncol 2007; 8(10):889-97

Gallego-Ortega D, Ramirez de Molina A, Gutierrez R, Ramos MA. Sarmentero J, Cejas P, Nistal M, Lacal JC. Generation and characterisation of monoclonal antibodies against choline kinase and its potential use as diagnostic tools in cancer. Int J Oncol 2006; 29(2):335-40.

Ramírez de Molina A, Gallego-Ortega D, Sarmentero J, Bañez-Coronel M, Lacal JC. Choline Kinase is a novel oncogene that potentiates RhoA-induced carcinogenesis. Cancer Res, 2005; 65(13): 5647-5653.

Dr David Gallego-Ortega




© Garvan Institute 2013