Sandra W. Ryeom, Ph.D.

faculty photo
Associate Professor of Cancer Biology
Department: Cancer Biology
Graduate Group Affiliations

Contact information
Room 756 BRB II/III
Department of Cancer Biology
Abramson Family Cancer Research Institute
421 Curie Boulevard
Philadelphia, PA 19104
Office: 215-573-5857
Fax: 215-573-2014
Lab: 215-573-5872
Education:
B.A. (Physics)
Wellesley College, 1989.
Ph.D. (Cell Biology and Genetics)
Cornell University, 1996.
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Description of Research Expertise

My 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 Publications

Lu J, Cao LL, Xu Y, Huang XY, Cho SJ, Ashktorab H, Smoot DT, Li P, Zheng CH, Kim JW, Ryeom SW, Yoon SS, Yoon C, Huang CM.: FOXC1 modulates stem-like cell properties and chemoresistance through Hedgehog and EMT signaling in gastric adenocarcinoma. Mol Ther. 14, Sept 2021.

Yoon C, Lu J, Ryeom SW, Simon MC, Yoon SS.: PIK3R3, part of the regulatory domain of PI3K, is upregulated in sarcoma stem-like cells and promotes invasion, migration, and chemotherapy resistance. Cell Death Dis. 12, July 2021.

Lu Z, Ortiz A, Verginadis II, Peck AR, Zahedi F, Cho C, Yu P, DeRita RM, Zhang H, Kubanoff R, Sun Y, Yaspan AT, Krespan E, Beiting DP, Radaelli E, Ryeom SW, Diehl JA, Rui H, Koumenis C, Fuchs SY.: Regulation of intercellular biomolecule transfer-driven tumor angiogenesis and responses to anticancer therapies. J. Clin Invest 131: e144225, May 2021.

Hoffman RK, Kim BJ, Shah PD, Carver J, Ky B, Ryeom S.: Damage to cardiac vasculature may be associated with breast cancer treatment-induced cardiotoxicity. Cardiooncology 19: 15, April 2021.

Lu J, Bang H, Kim SM, Cho SJ, Ashktorab H, Smoot DT, Zheng CH, Ryeom SW, Yoon SS, Yoon C, Lee JH. : Lymphatic metastasis-related TBL1XR1 enhances stemness and metastasis in gastric cancer stem-like cells by activating ERK1/2-SOX2 siganaling. Oncogene 40: 922-936, February 2021.

Yoon C, Lu J, Yi BC, Chang KK, Simon MC, Ryeom S, Yoon SS: PI3K/Akt pathway and Nanog maintain cancer stem cells in sarcomas. Oncogenesis 10: 12, January 2021.

Muramatsu M, Nakagawa S, Osawa T, Toyono T, Uemura A, Kidoya H, Takakura N, Usui T, Ryeom S, Minami T.: Loss of Down Syndrome Critical Region-1 Mediated-Hypercholesterolemia Accelerates Corneal Opacity Via Pathological Neovessel Formation. Arterioscler Thromb Vasc Biol August 2020.

Lin JX, Yoon C, Li P, Ryeom SW, Cho SJ, Zheng CH, Xie JW, Wang JB, Lu J, Chen QY, Yoon SS, Huang CM.: CDK5RAP3 as tumour suppressor negatively regulates self-renewal and invasion and is regulated by ERK1/2 signalling in human gastric cancer. Br. J. Cancer July 2020.

Gui J, Zahedi F, Ortiz A, Cho C, Katlinski KV, Alicea-Torres K, Li J, Todd L, Zhang H, Beiting DP, Sander C, Kirkwood JM, Snow BE, Wakeham AC, Mak TW, Diehl JA, Koumenis C, Ryeom SW, Stanger BZ, Puré E, Gabrilovich DI, Fuchs SY.: Activation of p38alpha stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs. Nature Cancer 1: 603-619, June 2020.

Yoon 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 Research 17: 1945, September 2019.

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Last updated: 09/23/2021
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