Mihaela Skobe, PhD Email Mihaela Skobe
- ASSOCIATE PROFESSOR | Oncological Sciences
Dr. Skobe obtained her bachelor’s degree in Molecular Biology at the University of Zagreb (Croatia), and completed her PhD in Cell Biology at the German Cancer Research Center in Heidelberg and at the University of Darmstadt (Germany). Her PhD thesis focused on the role of the microenvironment in the early stages of skin carcinogenesis, and demonstrated the fundamental role of activated stromal cells in inducing tumor growth and invasiveness. Her early studies of tumor angiogenesis were among the first to show the effectiveness of VEGFR-2 inhibition in preclinical models of cancer. Following her postdoctoral work at the Massachusetts General Hospital/Harvard Medical School, she joined the Department of Oncological Sciences at the Icahn School of Medicine at Mount Sinai in New York, where she began and built a research program focused on cancer metastasis and lymphatic vasculature. Dr. Skobe has pioneered the field of tumor lymphangiogenesis, and her discoveries have drawn major attention to the importance of lymphatic vasculature in cancer. She serves on numerous national and international advisory committees and review boards, has been the recipient of several awards, and was honored by the Lymphatic Research Foundation for her exceptional contributions to the field of lymphatic research.
Cancer, Chemokines, Growth Factors and Receptors, Lymphangiogenesis, Metastasis
Multi-Disciplinary Training Areas
Cancer Biology [CAB], Immunology [IMM]
BS, University of Zagreb
PhD, German Cancer Research Center in Heidelberg and University of Darmstadt
Postdoc, Harvard Medical School and Massachussetts General Hospital
Main research focus is on deciphering the interplay between the lymphatic vasculature and cancer cells, whose interaction is important in cancer progression and metastasis. The presence of metastases in the lymphatic system is strongly correlated with negative patient prognosis, and for most cancers lymph node status is one of the key criteria for determining the stage of cancer progression. Our research addresses a fundamental question in cancer biology - why is lymphatic metastasis associated with the progression of the disease and reduced patient survival? There are two broad areas of interest: (1) understanding the factors which control lymphatic metastasis and (2) understanding the molecular mechanisms which control lymphangiogenesis and lymphatic function in health and disease. Current research includes studies of (i) lymphangiogenesis, (ii) the lymphatic vascular niche and its influence on metastasis, (iii) mechanisms of tumor dissemination through the lymphatic system, and (iv) the role of lymphatic endothelium in immunoregulation, among others. Elucidating the molecular basis of metastasis is key for the development of new approaches to diagnose and treat metastatic disease. Furthermore, understanding the mechanisms that control the growth and function of the lymphatic vasculature has important implications towards a vast array of diseases that exhibit lymphatic vessel abnormalities.
Mirela Matokanovic, PhD (postdoctoral fellow)
Benedicte Lenoir, PhD (postdoctoral fellow)
Anita Rogic, MS (research associate)
Gibot L, Galbraith T, Kloos B, Das S, Lacroix DA, Auger FA, Skobe M. Cell-based approach for 3D reconstruction of lymphatic capillaries in vitro reveals distinct functions of HGF and VEGF-C in lymphangiogenesis. Biomaterials 2016 Feb; 78.
Podgrabinska S, Skobe M. Role of lymphatic vasculature in regional and distant metastases. Microvascular Research 2014 Sep; 95: 46-52.
Serasinghe MN, Missert DJ, Asciolla JJ, Podgrabinska S, Wieder SY, Izadmehr S, Belbin G, Skobe M, Chipuk JE. Anti-apoptotic BCL-2 proteins govern cellular outcome following B-RAF(V600E) inhibition and can be targeted to reduce resistance. Oncogene 2014 Mar;: 1-11.
Zhao Y, van Rooy I, Hak S, Fay F, Tang J, Davies Cd, Skobe M, Fisher EA, Radu A, Fayad ZA, de Mello Donegá C, Meijerink A, Mulder WJ. Near-infrared fluorescence energy transfer imaging of nanoparticle accumulation and dissociation kinetics in tumor-bearing mice. ACS Nano 2013 Nov; 7(11).
Das S, Sarrou E, Podgrabinska S, Cassella M, Mungamuri SK, Feirt N, Gordon R, Nagi CS, Wang Y, Entenberg D, Condeelis J, Skobe M. Tumor cell entry into the lymph node is controlled by CCL1 chemokine expressed by lymph node lymphatic sinuses. The Journal of Experimental Medicine 2013; 210: 1509-1528.
Das S, Ladell DS, Podgrabinska S, Ponomarev V, Nagi C, Fallon JT, Skobe M. Vascular endothelial growth factor-C induces lymphangitic carcinomatosis, an extremely aggressive form of lung metastases. Cancer Research 2010; 70: 1814-1824.
Podgrabinska S, Kamalu O, Mayer L, Shimaoka M, Snoeck H, Randolph GJ, Skobe M. Inflamed lymphatic endothelium suppresses dendritic cell maturation and function via Mac-1/ICAM-1-dependent mechanism. Journal of Immunology 2009; 183: 1767-1779.
Skobe M, Dana R. Blocking the path of lymphatic vessels. Nature Medicine 2009; 15: 993-994.
Furtado GC, Marinkovic T, Martin AP, Garin A, Hoch B, Hubner W, Chen BK, Genden E, Skobe M, Lira SA. Lymphotoxin beta receptor signaling is required for inflammatory lymphangiogenesis in the thyroid. PNAS 2007; 104: 5026-5031.
Shawber CJ, Funahashi Y, Francisco E, Vorontchikhina M, Kitamura Y, Stowell SA, Borisenko V, Feirt N, Podgrabinska S, Shiraishi K, Chawengsaksophak K, Rossant J, Accili D, Skobe M, Kitajewski J. Notch alters VEGF responsiveness in human and murine endothelial cells by direct regulation of VEGFR-3 expression. The Journal of Clinical Investigation 2007; 117: 3369-3382.
Angeli V, Ginhoux F, Llodrà J, Quemeneur L, Frenette PS, Skobe M, Jessberger R, Merad M, Randolph GJ. B cell-driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity 2006; 24: 203-215.
Roberts N, Kloos B, Cassella M, Podgrabinska S, Persaud K, Wu Y, Pytowski B, Skobe M. Inhibition of VEGFR-3 activation with the antagonistic antibody more potently suppresses lymph node and distant metastases than inactivation of VEGFR-2. Cancer Research 2006; 66: 2650-2657.
Pytowski B, Goldman J, Persaud K, Wu Y, Witte L, Hicklin DJ, Skobe M, Boardman KC, Swartz MA. Complete and specific inhibition of adult lymphatic regeneration by a novel VEGFR-3 neutralizing antibody. Journal of the National Cancer Institute 2005; 97: 14-21.
Sugaya M, Watanabe T, Yang A, Starost MF, Kobayashi H, Atkins AM, Borris DL, Hanan EA, Schimel D, Bryant MA, Roberts N, Skobe M, Staskus KA, Kaldis P, Blauvelt A. Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter. Blood 2005; 105: 2356-2363.
Pepper MS, Skobe M. Lymphatic endothelium: Morphological, molecular and functional properties. The Journal of Cell Biology 2003; 163: 209-213.
Rafii S, Skobe M. Splitting vessels: Keeping lymph apart from blood. Nature Medicine 2003; 9: 166-168.
Podgrabinska S, Braun P, Velasco P, Kloos B, Pepper MS, Skobe M. Molecular characterization of lymphatic endothelial cells. PNAS 2002; 99: 16069-16074.
Szuba A, Skobe M, Karkkainen MJ, Shin WS, Beynet DP, Rockson NB, Dakhil N, Spilman S, Goris ML, Strauss HW, Quertermous T, Alitalo K, Rockson SG. Therapeutic lymphangiogenesis with human recombinant VEGF-C. FASEB Journal 2002; 16: 1985-1987.
Skobe M, Hamberg LM, Hawighorst T, Schirner M, Wolf GL, Alitalo K, Detmar M. Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. The American Journal of Pathology 2001; 159: 893-903.
Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K, Detmar M. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nature Medicine 2001; 7: 192-198.
Skobe M, Fusenig NE. Tumorigenic conversion of immortal human keratinocytes through stromal cell activation. PNAS 1998; 95: 1050-1055.
Skobe M, Rockwell P, Goldstein N, Vosseler S, Fusenig NE. Halting angiogenesis suppresses carcinoma cell invasion. Nature Medicine 1997; 3: 1222-1227.
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