Sandra W. Ryeom, Ph.D.
Department of Cancer Biology
Abramson Family Cancer Research Institute
421 Curie Boulevard
Philadelphia, PA 19104
Wellesley College, 1989.
Ph.D. (Cell Biology and Genetics)
Cornell University, 1996.
Description of Research ExpertiseMy lab has been focused on understanding the role of the vasculature in promoting tumor progression and metastasis. Using mouse models of cancer, primary endothelial cells and molecular and cell biological approaches, we have been investigating the contributions of the calcineurin-NFAT signaling pathway towards activation of the vascular endothelium during tumor angiogenesis leading to tumor progression and metastasis. Calcineurin is a calcium regulated ser/thr phosphatase that regulates a number of physiological processes, most notably in T cells and neurons. Upon activation, calcineurin dephosphorylates members of the NFAT family, triggering their nuclear entry and transactivation of targets including pro-angiogenic genes in endothelial cels. One of the major contributions of my lab to the tumor microenvironment field is the critical importance of the calcineurin-NFAT pathway as an intracellular mediator of vascular endothelial growth factor (VEGF) activation in endothelial cells during pathologic angiogenesis. Anti-angiogenic cancer therapy has been focused primarily on targeting VEGF or its receptors and has been largely unsuccessful. Our work offers intracellular targets downstream of VEGF as possible therapeutic options.
My lab is also investigating the role of calcineurin-NFAT in endothelial cells in early metastatic sites in the lung and liver and identifying relevant NFAT-dependent targets promoting metastatic colonization and expansion. Further, we have begun to examine the role of the calcineurin-NFAT pathway in stromal cells during metastasis and are investigating the ‘stromagenic switch’ during tumor progression. Similar to the concept of the angiogenic switch when the balance of pro- and anti-angiogenic proteins shift towards a pro-angiogenic phenotype triggering the expansion of blood vessel growth or tumor angiogenesis, it is also becoming evident that stromal cells in the tumor microenvironment become activated to promote tumor growth and metastasis. We will identify cellular and molecular mechanisms by which stromal cells become activated and primed to permit metastatic tumor cell seeding. Further, my lab will also investigate cross-talk between stromal cells and endothelial cells in early metastatic sites and define the contribution of calcineurin-NFAT targets in stromal cells and endothelial cells towards this cross-talk.
For many years, it has been assumed that endothelial cells from different organs were similar in their activation, regulation and output of secreted factors during tumor growth and metastasis. Studies in our lab indicate that endothelial cells from different organ environments are unique and respond differently to pro-angiogenic factors producing organ specific secretomes. Another area of interest in the lab is to understand the contribution of endothelial cells in different organs towards maintaining stem cells populations. For example, my lab has identified the testicular endothelium as the critical accessory cell in the spermatogonial stem cell niche providing the factors necessary to maintain spermatogonial stem cell identity. We are examining endothelial cells in other organs to understand their contribution in stem cell niches as well as the role of organ specific endothelium in mediating metastatic tropism.
Selected PublicationsYoon C, Till J, Cho SJ, Chang KK, Lin JX, Huang CM, Ryeom S, Yoon SS.: KRAS Activation in Gastric Adenocarcinoma Stimulates Epithelial-to-Mesenchymal Transition to Cancer Stem-Like Cells and Promotes Metastasis. Mol. Cancer Res. 17: 1945, September 2019.
Kim YH, Oh MG, Bhang DH, Kim BJ, Jung SE, Kim SM, Dohr G, Kim SU, Ryeom S, Ryu BY.: Testicular endothelial cells promote self-renewal of spermatogonial stem cells in rats. Biol. Reprod. 101: 360, August 2019.
Lieberman A, Barrett R, Kim J, Zhang KL, Avery D, Monslow J, Kim H, Kim BJ, Puré E, Ryeom S.: Deletion of Calcineurin Promotes a Protumorigenic Fibroblast Phenotype. Cancer Res. 79: 3928, AUgust 2019.
Ryu MO, Kim BG, Choi US, Baek KH, Song YK, Li Q, Seo KW, Ryeom S, Youn HY, Bhang DH: Extracellular cyclic adenosine monophosphate-dependent protein kinase A autoantibody and C-reactive protein as serum biomarkers for diagnosis of cancer in dogs. Vet Comp Oncology March 2019.
Rowbotham SP, Li F, Dost AFM, Louie SM, Marsh BP, Pessina P, Anbarasu CR, Brainson CF, Tuminello SJ, Lieberman A, Ryeom S, Schlaeger TM, Aronow BJ, Watanabe H, Wong KK, Kim CF.: H3K9 methyltransferases and demethylases control lung tumor-propagating cells and lung cancer progression. Nature Communication November 2018.
Bhang DH, Kim BJ, Kim BG, Schadler K, Baek KH, Kim YH, Hsiao W, Ding BS, Rafii S, Weiss MJ, Chou ST, Kolon TF, Ginsberg JP, Ryu BY, Ryeom S.: Testicular endothelial cells are a critical population in the germline stem cell niche. Nature Communication October 2018.
Tilll JE, Yoon SS, Ryeom S: E-cadherin and K-ras: implicatoins of a newly developed model of gastric cancer. Oncoscience 4: 162-163, November 2017.
Baek KH and Ryeom S: Detection of Oncogene-Induced Senescence In Vivo. Methods in Molecular Biology 1534: 185-198, November 2017.
Till JE, Yoon C, Kim BJ, Roby K, Addai P, Jonokuchi E, Tang LH, Yoon SS, Ryeom S. : Oncogenic KRAS and p53 loss drive gastric tumorigenesis in a new mouse model of gastric cancer and can be attenuated by E-cadherin expression Cancer Research 77: 5349-5359, October 2017.
Yoon C, Cho SJ, Chang KK, Park DJ, Ryeom SW, Yoon SS.: Role of Rac1 Pathway in Epithelial-to-Mesenchymal Transition and Cancer Stem-like Cell Phenotypes in Gastric Adenocarcinoma. Molecular Cancer Research May 2017.