Leo Price
Postdoc / guest
- Name
- Dr. L.S. Price
- Telephone
- 071 5272727
- lsprice@lacdr.leidenuniv.nl
Dr. Leo Price is senior staff member at the Division of Drug Discovery & Safety and Chief Scientific Officer at OcellO.
My early research centered on a general theme of GTPase signalling, how these important molecular switches are regulated and how they modulate cell behaviour. This began with my Ph.D. research in the group of Anna Koffer, which focused on the role of G-proteins in histamine secretion from mast cells and resulted in the identification of Rho-family GTPases as key regulators of secretion. My postdoc research began in Martin Schwartz’ lab at the Scripps Institute in San Diego and focused on signalling by integrins, a family of cell surface receptors for the extracellular matrix. We identified a GTPase signalling pathway that relays intracellular signals from integrins to kinases and subsequent changes in cell migration. My research continued in this vein at the Netherlands Cancer Institute (NKI) in Amsterdam and the University Medical Center, Utrecht.
With a number of active collaborations my work here in the Division of Toxicology includes the role of adhesion and adhesion signalling in tissue organisation and maintenance and also the pivotal role of adhesion in certain clinically relevant conditions including renal failure and toxicity. Relevant research requires appropriate experimental models. For example, the majority of potential drugs that pass in vitro reporter-assay screening fail in animal tests. It is not surprising that cells cultured in a monolayer on a plastic dish will respond differently to cells growing in the highly complex environment of animal tissues. A degree of complexity can be reconstituted in vitro by culturing cells in three-dimensional matrices. We use various in vitro 3D cell models to investigate cell-cell and cell-matrix interactions, how these control processes such as epithelial morphogenesis (
see the movie), kidney epithelial cell function and tumour invasion and how these are disrupted during toxic stress responses. A particular focus is the application of functional genomics and high throughput screening to identify the genes and pathways involved in these processes.
Postdoc / guest
- Faculty of Science
- LACDR
- Divisie Cell systems and Drug Safety
- Koedoot E., Wolters L., Smid M., Stoilov P., Burger G.A., Herpers B.H.A., Yan K., Price L.S., Martens J.W.M., Le Dévédec S.E. & Water B. van de (2021), Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy, Scientific Reports 11: 7529.
- Booij T.H., Leonhard W.N., Bange H., Yan K., Fokkelman M., Plugge A.J., Veraar K.A.M., Dauwerse J.G., Westen G.J.P. van, Water B. van de, Price L.S. & Peters D.J.M. (2020), In vitro 3D phenotypic drug screen identifies celastrol as an effective in vivo inhibitor of polycystic kidney disease, Journal of Molecular Cell Biology 12(8): 644-653.
- Malas T.B., Leonhard W.N., Bange H., Granchi Z., Hettne K.M., Westen G.J.P. van, Price L.S., Hoen P.A.C. 't & Peters D.J.M. (2020), Prioritization of novel ADPKD drug candidates from disease-stage specific gene expression profiles, EBioMedicine 51: 102585.
- Hiemstra S., Ramaiahgari S.C., Wink S., Callegaro G., Coonen M., Meerman J., Jennen D., Nieuwendijk K. van den, Dankers A., Snoeys J., Bont H. de, Price L. & Water B. van de (2019), High-throughput confocal imaging of differentiated 3D liver-like spheroid cellular stress response reporters for identification of drug-induced liver injury liability, Archives of Toxicology 93(10): 2895-2911.
- Booij T.H., Price L.S. & Danen E.H.J. (2019), 3D Cell-Based Assays for Drug Screens: Challenges in Imaging, Image Analysis, and High-Content Analysis, Slas Discovery 24(6): 615-627.
- Booij T.H., Bange H., Leonhard W.N., Yan K., Fokkelman M., Kunnen S.J., Dauwerse J.G., Qin Y., Water B. van de, Westen G.J.P. van, Peters D.J.M. & Price L.S. (2017), High-Throughput Phenotypic Screening of Kinase Inhibitors to Identify Drug Targets for Polycystic Kidney Disease, Slas Discovery 22(8): 974-984.
- Booij T.H., Klop M.J., Yan K., Szántai-Kis C., Szokol B., Orfi .L., Water B. van de, Keri G. & Price L.S. (2016), Development of a 3D Tissue Culture-Based High-Content Screening Platform That Uses Phenotypic Profiling to Discriminate Selective Inhibitors of Receptor Tyrosine Kinases, Journal of biomolecular screening 21(9): 912-922.
- Baranski Z., Booij T.H., Cleton-Jansen A.M., Price L.S., Water B. van de, Bovee J.V.M.G., Hogendoorn P.C.W. & Danen E.H.J. (2015), Aven-mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in conventional osteosarcoma, The journal of Pathology 236(3): 348-359.
- Baranski Madrigal Z., Booij T.H., Jong Y. de, Oosterwijk J. van, Cleton A.-M., Price L.S., Water B. van de, Bovee J.V.M.G., Hogendoorn P.C.W. & Danen E.H.J. (2015), Aven-mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in osteosarcoma cells, Cancer Research 75(15): 3780.
- Di Z., Klop M.J.D., Rogkoti V.M., Le Dèvèdec S.E., Water B. van de, Verbeek F.J., Price L.S. & Meerman J.H.N. (2014), Ultra High Content Image Analysis and Phenotype Profiling of 3D Cultured Micro-Tissues, PLoS ONE 9(10): e109688.
- Graauw M. de, Cao L., Winkel L., Miltenburg M.H.A.M. van, Dévédec S.E. le, Klop M., Yan K., Pont C.M., Rogkoti V.M., Tijsma A., Chaudhuri A., Lalai R.A., Price L.S., Verbeek F.J. & Water B. van de (2014), Annexin A2 depletion delays EGFR endocytic trafficking via cofilin activation and enhances EGFR signaling and metastasis formation, Oncogene 33(20): 2610-2619.
- Ramaiahgari S.C., Braver M.W. den, Herpers B., Terpstra V., Commandeur J.N., Water B. van de & Price L.S. (2014), A 3D in vitro model of differentiated HepG2 cell spheroids with improved liver-like properties for repeated dose high-throughput toxicity studies, Archives of Toxicology 88(5): 1083-1095.
- Stokman G., Qin .Y., Booij T.H., Ramaiahgari S.C., Lacombe M., Dolman M.E., Dorenmalen K.M. van, Teske G.J., Florquin S., Schwede F., Water B. van de, Kok R.J. & Price L.S. (2014), Epac-Rap signaling reduces oxidative stress in the tubular epithelium, Journal of the American Society of Nephrology 25(7): 1474-1485.
- Truong H.H., Sonneville J. de, Ghotra V.P., Xiong J., Price L., Hogendoorn P.C., Spaink H.P., Water B. van de & Danen E.H. (2012), Automated microinjection of cell-polymer suspensions in 3D ECM scaffolds for high-throughput quantitative cancer invasion screens, Biomaterials 33(1): 181-188.
- Verissimo C.S., Cheng S., Puigvert J.C., Qin Y., Vroon A., Deutekom J. van, Price L.S., Danen E.H., Water B. van de, Fitzsimons C.P. & Vreugdenhil E. (2012), Combining doublecortin-like kinase silencing and vinca alkaloids results in a synergistic apoptotic effect in neuroblastoma cells, Journal of Pharmacology and Experimental Therapeutics 342(1): 119-130.
- Qin Y., Stokman G., Yan K., Ramaiahgari S.C., Verbeek F.J., Graauw M. de, Water B. van de & Price L.S. (2012), cAMP signalling protects proximal tubular epithelial cells from cisplatin-induced apoptosis via activation of Epac, British Journal of Pharmacology 165(4b): 1137-1150.
- Zhang Y., Moerkens M., Ramaiahgari S., Bont H.J.G.M. de, Price L., Meerman J.H.N. & Water B. van de (2011), Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes, Breast cancer research 13(3): R52.
- Qin Y., Alderliesten M.C., Stokman G., Pennekamp P., Bonventre J.V., Heer E. de, Ichimura T., De Graauw M., Price L.S. & Water B. van de (2011), Focal adhesion kinase signaling mediates acute renal injury induced by ischemia/reperfusion, The American Journal of Pathology 179(6): 2766-2778.
- Stokman G., Qin Y., Genieser H.G., Schwede F., Heer E. de, Bos J.L., Bajema I.M., Water B. van de & Price L.S. (2011), Epac-Rap signaling reduces cellular stress and ischemia-induced kidney failure, Journal of the American Society of Nephrology 22(5): 859-872.
- Screening of compounds for the pharmaceutical and biotech industries