faculty photo

Sandra W. Ryeom

Assistant Professor of Cancer Biology
Department: Cancer Biology

Contact information
Room 752 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
Graduate Group Affiliations
B.A. (Physics)
Wellesley College, 1989.
Ph.D. (Cell Biology and Genetics)
Cornell University, 1996.
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Description of Research Expertise

Research Interests: My lab is interested in understanding the molecular mechanisms that regulate the tumor microenvironment with a particular focus on the vasculature.

Key Words: Cancer, angiogenesis, tumor suppressors, calcineurin signaling, senescence, immune surveillance

Research Details:
The overarching goal of my laboratory is to understand how the tumor microenvironment is assembled and maintained, with particular focus on the generation and maintenance of the tumor blood supply – the process of tumor angiogenesis. Tumor angiogenesis is a dynamic process involving continuous elaboration and remodeling of blood vessels in the tumor microenvironment. It is driven by the precocious production of various angiogenic factors of which the best characterized is VEGF, an endothelial mitogen whose regulation and downstream effectors have been the focus of intense investigation for over a decade. However, angiogenesis is under constant restraint by a variety of endogenous inhibitors, and it has become clear that modulation of these inhibitors also plays a critical role in tumor angiogenesis but the mechanisms by which they do so are far less well understood.

Figure: Down syndrome and normal induced pluripotent stem cells (iPS) cells. Teratomas derived from Down syndrome iPS cells (top) show suppression of tumor angiogenesis as compared to those derived from normal iPS cells (bottom) as indicated by CD31 staining (red).

My laboratory is particularly interested in understanding how angiogenesis inhibitors act to limit endothelial cell activation and angiogenesis, how they are regulated by tumor suppressors and oncogenes, and how they might be used therapeutically to treat cancers.

Rotation projects include:
i) Understanding why Down syndrome individuals are protected against cancer and the role of the calcineurin inhibitor, DSCR1 in suppressing VEGF-mediated angiogenesis;
ii) Identifying new cell extrinsic tumor suppressor functions of p53 and p19ARF: regulation of the endogenous angiogenesis inhibitors thrombopsondin-1 and endostatin;
iii) Investigating a novel role for the endogenous angiogenesis inhibitor thrombospondin-1 in mediating oncogene-induced senescence;
iv) Immune surveillance and the role of the endogenous angiogenesis inhibitors thrombospondin-1 and endostatin in tumor immunity.

Lab Personnel:
Bang-jin Kim, Ph.D.
Katie Sturgeon, M.D., Ph.D.

Graduate Students:
Allyson Lieberman
Kerry Roby
Jacob Till
Alice Zhou

Undergraduate Students:
Prince Addai
Evan Jonokuchi
Jaeyoung Shin

Selected Publications

Lee JH, Bhang DH, Beede A, Huang TL, Stripp BR, Bloch KD, Wagers AJ, Tseng YH, Ryeom S, Kim CF: An endothelial cell BMP4-NFATc1-Thrombospondin-1 axis directs lung stem cell differentiation in mice. Cell 156(3): 440-455, 2014.

Zhou AY, Ryeom SW: Cyclosporin A Promotes Tumor Angiogenesis in a Calcineurin-Independent Manner by Increasing Mitochondrial Reactive Oxygen Species. Mol. Cancer Res. 12(11): 1663-1667, 2014.

Schadler KL, Crosby EJ, Zhou AY, Bhang DH, Braunstein L, Baek KH, Crawford D, Crawford A, Angelosanto J, Wherry EJ, Ryeom S: Immunosurveillance by anti-angiogenesis: tumor growth arrest by T cell-derived thrombospondin-1. Cancer Res. 74: 2171-2181, 2014.

Zaslavsky A, Chou ST, Schadler K, Lieberman A, Pimkin M, Kim YJ, Baek KH, Aird WC, Weiss MJ, Ryeom S: The calcineurin-NFAT pathway negatively regulates megakaryopoiesis. Blood 121(16): 3205-3215, 2013.

Minami T, Jiang S, Schadler K, Suehiro J, Osawa T, Oike Y, Miura M, Naito M, Kodama T, Ryeom S: The calcineurin-NFAT-angiopoietin-2 signaling axis in lung endothelium is critical for the establishment of lung metastases. Cell Rep. 4(4): 709-723, 2013.

Baek KH, Bhang D, Zaslavsky A, Wang LC, Vachani A, Kim CF, Albelda SM, Evan GI, Ryeom S: Thrombospondin-1 mediates oncogenic Ras-induced senescence in premalignant lung tumors. J. Clin. Invest. 123(10): 4375-4389, 2013.

Schmidt B, Lee HJ, Ryeom S, Yoon SS: Combining Bevacizumab with Radiation or Chemoradiation for Solid Tumors: A Review of the Scientific Rationale, and Clinical Trials. Current Angiogenesis 1: 169-179, 2012.

Stewart KS and Ryeom S: Regulation of Tumor Angiogenesis by the Immune System. Current Angiogenesis 1: 88-97, 2012.

Ryeom S: The cautionary tale of the side effects of chronic Notch1 inhibition. J. Clin. Invest. 121(2): 508-509, 2011.

Becker CM, Beaudry P, Funakoshi T, Benny O, Zaslavsky A, Folkman J, D’Amato RJ, Ryeom S: Circulating endothelial progenitor cells are upregulated in a mouse model of endometriosis. Am. J. Pathol. 178(4): 1782-1791, 2011.

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Last updated: 10/06/2015
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