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Sophia Ran, Medical Microbiology, Immunology and Cell Biology Faculty - SIU School of Medicine


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Sophia Ran

Sophia Ran

Dr. Ran is a Professor in the Department of Medical Microbiology, Immunology and Cell Biology at SIU School of Medicine and a member of the Simmons Cancer Institute. Dr. Ran is a current member of the American Association of Cancer Research (AACR) and was a member of the Research Advisory Board of American Cancer Society, IL Division (2009-2012). She has also served on multiple grant review committees of national and international funding agencies from USA, Italy, Switzerland, Poland, Israel, Canada, and UK. She currently serves as a chartered member of the Tumor Microenvironment Study Section at the National Institute of Health. She also currently serves on the Editorial Boards of several journals including Frontiers in Vascular Physiology, Journal of Cancer Science and Therapy, Pathology Discovery and others. Dr. Ran was multiple times a member of the organizing committee for the bi-annual Simmons Cancer Institute Research Symposium and served on various committees at the SIU School of Medicine.


  • 1991-1992 Postdoctoral training in Cellular Physiology, The Hospital for Sick Children, Toronto, Canada
  • 1989-1991 Postdoctoral training in Ion Transport, University of Alabama at Birmingham, Alabama, USA
  • 1984-1989 Ph.D. in Biochemistry, the Weizmann Institute of Science, Rehovot, Israel
  • 1981-1983 M.S. in Immunology, Ben-Gurion University, Beer Sheva, Israel
  • 1979-1981 B.S. in Biology, Tel Aviv University, Tel Aviv, Israel

Research Focus

Main research interest: Breast Cancer • Tumor Physiology • Tumor Angiogenesis & Hematogenous Metastasis • Tumor Lymphangiogenesis & Lymphatic Metastasis • Inflammation and Cancer • Inflammatory Lymphangiogenesis • Lymphatic Endothelial Cell Progenitors • Tumor Models in vivo • Tumor Associated Macrophages • Chemotherapy & Chemoresistance • TLR4 Role in Cancer Progression and Metastasis

Main Projects

It is well known that metastasis is the main cause of mortality from cancer. Metastases are secondary tumors formed in organs other than the primary site. The goal of my lab is to delineate mechanisms that promote metastasis, a process that typically involves invasion of blood or lymphatic vessels located either near the tumor (i.e., peritumoral) or inside the tumor mass (i.e., intratumoral). In breast cancer and many other epithelial malignancies, tumor cells first establish colonies in lymph nodes prior to spreading to other organs. Lymphatic metastasis is strongly enhanced by generation of new lymphatic vessels, a complex process that my laboratory seeks to understand on the molecular, cellular, and systemic levels. We recently discovered that this process is primarily driven by tumor-mobilized immature myeloid cells that upon exposure to inflammatory stimuli differentiate towards lymphatic endothelial precursors dubbed M-LECP (Monocyte-derived Lymphatic Endothelial Cell Progenitors). M-LECP promote tumor lymphatics by both production of lymphangiogenic factors and structural contribution to the nascent vessels. The ability of tumors to recruit monocytes and differentiate them into M-LECP appears to directly relate to metastatic potential and correlate with resistance to therapy. We also recently discovered (PMID 25274031) that a commonly used anti-cancer drug paclitaxel has unexpected capacity to activate tumor epithelial cells and macrophages via Toll-like Receptor-4 (TLR4). Activation of this highly inflammatory pathway in malignant and tumor-associated cells protects tumor cells from chemotherapy and helps generating new vasculature with the help of monocyte-derived endothelial progenitor cells. We expect that these studies will advance understanding of generation of new tumor vessels which, in turn, will promote development of new anti-metastatic drugs.

General Laboratory Techniques

Cell culture of human and mouse tumor epithelial cell lines; generation of stably transfected cell lines; tissue culture of primary endothelial cells, bone marrow-derived monocytes, and macrophages; directional migration assays; real-time PCR and in-house construction of gene profiling arrays; protein analysis on western blot; growth of hybridoma lines, isolation and characterization of monoclonal antibodies; ELISA; luciferase-based reporter assays; immunofluorescence and immunohistochemistry; tissue and cell imaging; flow cytometry; analysis of animal models of breast cancer and metastasis

Selected Publications from 53 total:

  1. Volk-Draper, L.D., Hall, K., Griggs, C., Rajput, S., Kohio, P., DeNardo, D.G., and Ran, S. (2014) Paclitaxel therapy promotes breast cancer metastasis in a TLR4-dependent manner. Cancer Research, 74(19):5421-5434. PMID 25274031
  2. Flister, M.J., Endres, B.T., Rudemiller, N., Sarkis, A. B., Santarriaga, S., Lemke, A., Geurts , A. M., Moreno, C., Ran, S., Tsaih, S. W., De Pons, J., Carlson, D., Tan, W., Fahrenkrug, S. C., Lazarova, Z., Lazar, J., LaViolette, P. S., Dwinell, M.B., Shull, J.D., and Jacob, H.J. (2014) CXM - a new tool for mapping breast cancer risk in the tumor microenvironment. Cancer Research, 74(22):6419-6429. PMID 25172839
  3. Mehner, C., Hockla, A., Miller, E., Ran, S., Radisky, D., and Radisky, E. (2014) Tumor cell-produced matrix metalloproteinase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer. Oncotarget, 5(9):2736-2749. PMID 24811362
  4. Engelmann, D., Mayoli-Nussle, D., Mayrhofer, C., Furst, K., Alla, V., Stoll, A., Abshagen, K., Vollmar, B., Ran, S., and Putzer, B.M. (2013) E2F1 Promotes Angiogenesis through the VEGF-C/VEGFR-3 Axis in a Feedback Loop for Cooperative Induction of PDGF-B. Journal of Molecular Cell Biology, 5(6):391-403. PMID 24014887
  5. Rajput, S., Volk-Draper, L.D. and Ran, S. (2013) TLR4 is a novel determinant of the response to paclitaxel in breast cancer. Molecular Cancer Therapeutics,12(8):1676-1687. This article was featured in Highlights of this journal issue 12 on page 1379. PMID 23720768
  6. Volk-Draper, L.D., Rajput, S., Hall, K.L., Wilber, A. and Ran, S. (2012) Novel model for triple-negative basaloid breast cancer: behavior in vivo and response to therapy. Neoplasia, 14(10):926-942.  PMID 23097627
  7. Ran, S. and Montgomery, K. E. (2012) Macrophage-Mediated Lymphangiogenesis: The Emerging Role of Macrophages as Lymphatic Endothelial Progenitors. Cancers, 4(3):618-657. PMID 22946011
  8. Hall, K.L., Volk-Draper, L.D., Flister, M.J. and Ran, S. (2012) New model of macrophage acquisition of the lymphatic endothelial phenotype. PLoS ONE, 7(3): e31794. PMID  22396739
  9. Yoshioka, S., King, M.L., Ran, S., Okuda, H., MacLean II, J.A., McAsey, M.E., Sugino, N., Watabe, K. and Hayashi, K. (2012) WNT7A regulates tumor growth and progression in ovarian cancer through the WNT/β-catenin pathway. Molecular Cancer Research, Epub ahead of print, PMID 22232518 
  10. Mohamedali, K.A., Ran, S., Gomez-Manzano, C., Ramdas, L., Xu, J., Kim, S., Cheung, L. H., Hittelman, W.N., Zhang, W., Waltenberger, J., Thorpe, P.E. and Rosenblum, M.G. (2011) Cytotoxicity of VEGF121/rGel on vascular endothelial cells resulting in inhibition of angiogenesis is mediated via VEGFR-2. BMC Cancer 11(1):358. PMID 21849059
  11. Ray, M.A., Trammell, R.A., Verhulst, S., Ran, S., Toth, L.A. (2011) Model development for the assessment of fatigue during chemotherapy in mice. Comparative Medicine, 61:119-130. PMID 21535922 
  12. Volk, L., Flister, M.J., Chihade, D., Desai, N., Trieu, V. and Ran, S. (2011) Synergy of nab-paclitaxel and bevacizumab in eradicating large orthotopic breast tumors and pre-existing metastases. Neoplasia, 13(4):327-38. PMID 21472137
  13. Flister, M.J., Volk, L. and  Ran, S. (2011) Characterization of Prox1 and VEGFR-3 expression and lymphatic phenotype in normal organs of mice lacking p50 subunit of NF-κB. Microcirculation, 18(2):85-101. PMID 21166921
  14. Hall, K. and Ran, S. (2010) Regulation of tumor angiogenesis by the local environment. Frontiers of Biosciences, 15:195-212. PMID 20036815
  15. Ran, S., Volk, L., Hall, K., and Flister, M.J. (2010) Lymphangiogenesis and lymphatic metastasis in breast cancer. Pathophysiology, 17:229-251. PMID 20036110
  16. Flister, M.J., Wilber, A., Hall, K., Iwata, C., Miyazono, K., Nisato, R.E., Pepper, M.S., David C. Zawieja, D.C. and Ran, S. (2010) Inflammation induces lymphangiogenesis through upregulation of VEGFR-3 mediated by NF-κB and Prox1. Blood 115 (2):418-429. PMID 19901262
  17. Cheng, J.M., Volk, L., Janaki, D.K., Vyakaranam S., Ran, S. and Rao, K.A. (2010) Tumor suppressive function of Rab25 in breast cancer. Int. J. Cancer, 126 (12): 2799-812. PMID 19795443

Book Editing

  1. "Tumor Angiogenesis" published in February 2012 by Open Access InTechOpen publisher, ISBN 978-953-51-0009-6, web address
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