faculty photo

Sandra W. Ryeom

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

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
Education:
B.A. (Physics)
Wellesley College, 1989.
Ph.D. (Cell Biology and Genetics)
Cornell University, 1996.
Post-Graduate Training
Postdoctoral Fellow , Department of Cell Biology, Harvard Medical School, Laboratory of Dr. Frank McKeon , 1997-2004.
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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

Jacob E. Till, Changhwan Yoon, Bang-Jin Kim, Kerry Roby, Prince Addai, Evan Jonokuchi, Laura H. Tang, Sam S. Yoon, Sandra Ryeom : 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.

Baek KH and Ryeom S: Detection of Oncogene-Induced Senescence In Vivo. Methods in Molecular Biology 1534: 185-198, November 2016.

Schadler Keri L, Thomas Nicholas J, Galie Peter A, Bhang Dong Ha, Roby Kerry C, Addai Prince, Till Jacob E, Sturgeon Kathleen, Zaslavsky Alexander, Chen Christopher S, Ryeom Sandra: Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy. Oncotarget 7(40): 65429-65440, October 2016.

Yoon Changhwan, Cho Soo-Jeong, Aksoy Bülent Arman, Park Do Joong, Schultz Nikolaus, Ryeom Sandra W, Yoon Sam S: Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells. Clinical Cancer Research 22(4): 971-83, Feb 2016.

Lehman SL, Cerniglia GJ, Johannes GJ, Ye J, Ryeom S, Koumenis C: Translational Upregulation of an Individual p21Cip1 Transcript Variant by GCN2 Regulates Cell Proliferation and Survival under Nutrient Stress. PLoS Genetics 11(6): e1005212, Jun 2015.

Casey SC, Vaccari M, Al-Mulla F, Al-Temaimi R, Amedei A, Barcellos-Hoff MH, Brown DG, Chapellier M, Christopher J, Curran CS, Forte S, Hamid RA, Heneberg P, Koch DC, Krishnakumar PK, Laconi E, Maguer-Satta V, Marongiu F, Memeo L, Mondello C, Raju J, Roman J, Roy R, Ryan EP, Ryeom S, Salem HK, Scovassi AI, Singh N, Soucek L, Vermeulen L, Whitfield JR, Woodrick J, Colacci A, Bisson WH, Felsher DW: The effect of environmental chemicals on the tumor microenvironment. Carcinogenesis 36 Suppl 1: S160-83, Jun 2015.

Goodson WH 3rd, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A, Lasfar A, Carnero A, Azqueta A, Amedei A, Charles AK, Collins AR, Ward A, Salzberg AC, Colacci A, Olsen AK, Berg A, Barclay BJ, Zhou BP, Blanco-Aparicio C, Baglole CJ, Dong C, Mondello C, Hsu CW, Naus CC, Yedjou C, Curran CS, Laird DW, Koch DC, Carlin DJ, Felsher DW, Roy D, Brown DG, Ratovitski E, Ryan EP, Corsini E, Rojas E, Moon EY, Laconi E, Marongiu F, Al-Mulla F, Chiaradonna F, Darroudi F, Martin FL, Van Schooten FJ, Goldberg GS, Wagemaker G, Nangami GN, Calaf GM, Williams G, Wolf GT, Koppen G, Brunborg G, Lyerly HK, Krishnan H, Ab Hamid H, Yasaei H, Sone H, Kondoh H, Salem HK, Hsu HY, Park HH, Koturbash I, Miousse IR, Scovassi AI, Klaunig JE, Vondráček J, Raju J, Roman J, Wise JP Sr, Whitfield JR, Woodrick J, Christopher JA, Ochieng J, Martinez-Leal JF, Weisz J, Kravchenko J, Sun J, Prudhomme KR, Narayanan KB, Cohen-Solal KA, Moorwood K, Gonzalez L, Soucek L, Jian L, D'Abronzo LS, Lin LT, Li L, Gulliver L, McCawley LJ, Memeo L, Vermeulen L, Leyns L, Zhang L, Valverde M, Khatami M, Romano MF, Chapellier M, Williams MA, Wade M, Manjili MH, Lleonart ME, Xia M, Gonzalez MJ, Karamouzis MV, Kirsch-Volders M, Vaccari M, Kuemmerle NB, Singh N, Cruickshanks N, Kleinstreuer N, van Larebeke N, Ahmed N, Ogunkua O, Krishnakumar PK, Vadgama P, Marignani PA, Ghosh PM, Ostrosky-Wegman P, Thompson PA, Dent P, Heneberg P, Darbre P, Sing Leung P, Nangia-Makker P, Cheng QS, Robey RB, Al-Temaimi R, Roy R, Andrade-Vieira R, Sinha RK, Mehta R, Vento R, Di Fiore R, Ponce-Cusi R, Dornetshuber-Fleiss R, Nahta R, Castellino RC, Palorini R, Abd Hamid R, Langie SA, Eltom SE, Brooks SA, Ryeom S, Wise SS, Bay SN, Harris SA, Papagerakis S, Romano S, Pavanello S, Eriksson S, Forte S, Casey SC, Luanpitpong S, Lee TJ, Otsuki T, Chen T, Massfelder T, Sanderson T, Guarnieri T, Hultman T, Dormoy V, Odero-Marah V, Sabbisetti V, Maguer-Satta V, Rathmell WK, Engström W, Decker WK, Bisson WH, Rojanasakul Y, Luqmani Y, Chen Z, Hu Z: Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis 36 Suppl 1: S254-96, Jun 2015.

Lehman SL, Ryeom S, Koumenis C: Signaling through alternative Integrated Stress Response pathways compensates for GCN2 loss in a mouse model of soft tissue sarcoma. Scientific Reports 5: 11781, Jun 2015.

Zhou Alice Yao, Ryeom Sandra: Cyclosporin A promotes tumor angiogenesis in a calcineurin-independent manner by increasing mitochondrial reactive oxygen species. Molecular Cancer Research 12(11): 1663-76, November 2014.

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Last updated: 11/03/2017
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