My lab is interested in understanding the molecular mechanisms that regulate the tumor microenvironment with a particular focus on the vasculature.
Cancer, angiogenesis, tumor suppressors, calcineurin signaling, senescence, immune surveillance
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.
Bang-jin Kim, Ph.D.
Katie Sturgeon, M.D., Ph.D.
Yoon C, Cho SJ, Aksoy BA, Park DJ, Schultz N, Ryeom S, Yoon SS: Chemotherapy resistance in diffuse type gastric adenocarcinoma is mediated by RhoA activation in cancer stem-like cells. Clinical Cancer Research 2015. Notes: [Epub ahead of print]
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, 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, 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, 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, 2015.
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. Molecular Cancer Research 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 Research 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.
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. Journal of Clinical Investigation 123(10): 4375-4389, 2013.
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Last updated: 11/16/2015
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