Ph.D. degree: The Feinberg Graduate School, Weizmann Institute of Science, Rehovot, Israel, Department of Biological Regulation
Thesis title: “In vivo MRI studies of angiogenesis in reproduction and embryonic development in transgenic mice”
My overarching interests are in the mechanisms by which the mammary epithelium and its interactions with the stromal microenvironment mediate normal mammary development as well as cancer transformation and dissemination. I am particularly interested in mammary epithelial (cancer) stem cells. I currently work on three collaborative projects: In the first project we found that Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis. They are exceptionally efficient in reconstituting mammary glands from single cells and their depletion significantly inflicts on the ability of the gland to undergo postatal organogenesis. We are now focusing on the role of these stem/progenitor cells in breast cancer. The second project examines how the adaptive immune system contributes to the regulation of normal mammary pubertal development. In this project, we focus on tissue antigen presenting cells and their communications with CD4+ T cells in mediating normal mammary postnatal organogenesis, which have implications for understanding immune surveillance. This project also raises interesting questions regarding possible roles for T cell dysfunction in early stages of breast cancer transformation. In the last project we are studying the early metastatic niche in the lungs of mammary-tumor bearing hosts, focusing on immune cells and extracellular matrix proteins that mediate the creation of such a niche, in support of metastatic seeding and growth. This study specifically aims at validating drug targets and designing therapeutics to treat metastatic disease.
1. The Cancer Stem Cell Niche: How Essential Is the Niche in Regulating Stemness of Tumor Cells? Plaks V, Kong N, Werb Z. Cell Stem Cell. 2015; 5;16(3):225-238.
2. Blastocyst implantation failure relates to impaired translational machinery gene expression. Plaks V, Gershon E, Zeisel A, Jacob-Hirsch J, Neeman M, Winterhager E, Rechavi G, Domany E, Dekel N. Reproduction. 2014;148(1):87-98.
3.Circulating Tumor Cells. Perspective. Plaks V, Koopman C.D and Werb Z. Science, 2013;341(6151):1186-8.
4. Matrix Metalloproteinase-9 Deficiency Phenocopies Features of Preeclampsia and Intrauterine Growth Restriction. Plaks V, Rinkenberger J, Dai J, Flannery M, Sund M, Kanasaki K, Ni W, Kalluri R and Werb Z. PNAS, 2013;110(27):11109-14.
5. Lgr5- expressing cells are sufficient and necessary for postnatal mammary gland organogenesis. Plaks V, Brenot A, Lawson DA, Linnemann JR, Van Kappel EC, Wong KC, de Sauvage F, Klein OD, Werb Z. Cell Reports, 2013; 3(1):70-8. Paper selected for the “Cell Reports Best of 2013” issue
6. Imaging Tumor-Stroma Interactions during Chemotherapy Reveals Contributions of the Microenvironment to Resistance. Nakasone ES, Askautrud HA, Kees T, Park JH, Plaks V, Ewald AJ, Fein M, Rasch MG, Tan YX, Qiu J, Park J, Sinha P, Bissell MJ, Frengen E, Werb Z, Egeblad M. Cancer Cell. 2012 Apr 17;21(4):488-503.
7. A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. Hunkapiller NM, Gasperowicz M, Kapidzic M, Plaks V, Maltepe E, Kitajewski J, Cross JC, Fisher SJ. Development. 2011 Jul;138(14):2987-98.
8. Survival and size are differentially regulated by placental and fetal PKBalpha/AKT1 in mice. Plaks V, Berkovitz E, Vandoorne K, Berkutzki T, Damari GM, Haffner R, Dekel N, Hemmings BA, Neeman M, Harmelin A. Biol Reprod. 2011 Mar;84(3):537-45. Epub 2010 Oct 27.
9. Functional phenotyping of the maternal albumin turnover in the mouse placenta by dynamic contrast-enhanced MRI. Plaks V, Sapoznik S, Berkovitz E, Haffner-Krausz R, Dekel N, Harmelin A, Neeman M. Mol Imaging Biol. 2011 Jun;13(3):481-92.
10. Bone vascularization and trabecular bone formation are mediated by PKB alpha/Akt1 in a gene-dosage-dependent manner: in vivo and ex vivo MRI. Vandoorne K, Magland J, Plaks V, Sharir A, Zelzer E, Wehrli F, Hemmings BA, Harmelin A, Neeman M. Magn Reson Med. 2010 Jul;64(1):54-64.
11. Matrix metalloproteinases: regulators of the tumor microenvironment. Kessenbrock K, Plaks V, Werb Z. Cell. 2010 Apr 2;141(1):52-67. Review.
12. Ferritin nanoparticles as magnetic resonance reporter gene. Cohen B, Ziv K, Plaks V, Harmelin A, Neeman M. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009 Mar-Apr;1(2):181-8. Review.
13. Uterine DCs are crucial for decidua formation during embryo implantation in mice. Plaks V, Birnberg T, Berkutzki T, Sela S, BenYashar A, Kalchenko V, Mor G, Keshet E, Dekel N, Neeman M, Jung S. J Clin Invest. 2008 Dec;118(12):3954-65. doi: 10.1172/JCI36682. Epub 2008 Nov 20.
14. Gap junctions in the ovary: expression, localization and function. Gershon E, Plaks V, Dekel N. Mol Cell Endocrinol. 2008 Jan 30;282(1-2):18-25. Epub 2007 Nov 19. Review.
15. Oocyte-directed depletion of connexin43 using the Cre-LoxP system leads to subfertility in female mice. Gershon E, Plaks V, Aharon I, Galiani D, Reizel Y, Sela-Abramovich S, Granot I, Winterhager E, Dekel N. Dev Biol. 2008 Jan 1;313(1):1-12. Epub 2007 Aug 31.
16. MRI detection of transcriptional regulation of gene expression in transgenic mice. Cohen B, Ziv K, Plaks V, Israely T, Kalchenko V, Harmelin A, Benjamin LE, Neeman M. Nat Med. 2007 Apr;13(4):498-503. Epub 2007 Mar 11.
17. Cloprostenol, a prostaglandin F(2alpha) analog, induces hypoxia in rat placenta: BOLD contrast MRI. Girsh E, Plaks V, Gilad AA, Nevo N, Schechtman E, Neeman M, Dekel N. NMR Biomed. 2007 Feb;20(1):28-39.
18. MRI analysis of angiogenesis during mouse embryo implantation. Plaks V, Kalchenko V, Dekel N, Neeman M. Magn Reson Med. 2006 May;55(5):1013-22.
19. WST11, a novel water-soluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution and vascular-targeted photodynamic activity using melanoma tumors as a model. Mazor O, Brandis A, Plaks V, Neumark E, Rosenbach-Belkin V, Salomon Y, Scherz A. Photochem Photobiol. 2005 Mar-Apr;81(2):342-51.
20. Homologous adaptation to oxidative stress induced by the photosensitized Pd-bacteriochlorophyll derivative (WST11) in cultured endothelial cells. Plaks V, Posen Y, Mazor O, Brandis A, Scherz A, Salomon Y. J Biol Chem. 2004 Oct 29;279(44):45713-20. Epub 2004 Aug 31.
21. Photodynamic therapy of established prostatic adenocarcinoma with TOOKAD: a biphasic apparent diffusion coefficient change as potential early MRI response marker. Plaks V, Koudinova N, Nevo U, Pinthus JH, Kanety H, Eshhar Z, Ramon J, Scherz A, Neeman M, Salomon Y. Neoplasia. 2004 May-Jun;6(3):224-33.