Sophia Ran, PhD

Contact
phone: 217.545.7026
sran@siumed.edu

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 has served on the Research Advisory Board of American Cancer Society and grant review committees of multiple funding agencies in USA, Italy, Switzerland, Poland, Israel, Canada, and UK. She also served as a chartered member of the Tumor Microenvironment study section at the National Institute of Health as well as an ad-hoc on multiple other NIH study sections. She served on the Editorial Boards of several journals including Frontiers in Vascular Physiology, Journal of Cancer Science and Therapy, Pathology Discovery and others. Dr. Ran currently serves on multiple committees at the SIU School of Medicine

Research Focus

Main Research Interest: Breast Cancer & Metastasis ¨ Tumor-induced Formation of Lymphatic Vessels ¨ Bone Marrow Derived Lymphatic Endothelial Progenitors ¨ Breast Cancer Mouse Models in vivo ¨ Tumor Macrophages ¨ Toll-like Receptor-4 (TLR4) ¨ Chemoresistance and Metastasis ¨ Tumor Microenvironment

Background for Main Projects

Metastases are secondary tumors that grow in organs other than the primary site. It is well established that metastatic lesions are primarily responsible for mortality from cancer. The goal of my lab is to delineate mechanisms that promote metastasis to lymph nodes, the first site in the metastatic cascade in breast and many other cancers. Expansion of tumor lymphatic vasculature significantly increases the rate of metastasis to the nodes. Therefore, we focus on understanding the process of generation of new lymphatic vessels at molecular and cellular levels. We discovered that this process is directly supported by tumor-recruited monocytes and macrophages that have been differentiated into lymphatic endothelial progenitors. We call these cells M-LECP which stands for Monocyte-derived Lymphatic Endothelial Cell Progenitors. M-LECP have combined properties of macrophages and lymphatic endothelial cells both of which contribute to new vessel formation. Generation of M-LECP in the bone marrow depends, among other factors, on activation of Toll-like Receptor-4 (TLR4). This receptor can be activated by a variety of ligands including paclitaxel, a common clinical anti-cancer drug. TLR4 activation in tumor cells by paclitaxel or other ligands promotes tumor cell survival and resistance to therapy. Our current projects are focused on understanding the TLR4-dependent and independent mechanisms driving differentiation of lymphatic endothelial progenitors, their recruitment to tumors, and their impact on tumor vessel formation and metastasis. We expect that these studies will advance understanding of how tumor vessels are formed which, in turn, will help development of new anti-metastatic drugs.  

Methods and Techniques Used in the Laboratory

Cell culture of human and mouse epithelial and endothelial cell lines; cell plasmid transfection and lentivirus infection; differentiation of myeloid and lymphatic cell lineages from stem and progenitor cells; migration assays; real-time PCR and in-house construction of gene arrays; protein analysis on Western blots; growth of hybridoma lines, isolation and characterization of  monoclonal antibodies; ELISA; luciferase-based reporter assays; immunofluorescence and immunohistochemistry; tissue and cell imaging; flow cytometry; breast cancer animal models including analysis of tumor growth, vessels and metastasis in vivo; various analyses of clinical cancer specimens.