Gender	Female
E-mail	mihaela.skobe@mssm.edu
Education and Training	Ph.D., University of Heidelberg
	B.S., University of Zagreb
	Postdoctoral Research, Harvard Medical School/Massachussetts General Hospital

Education and Training	Ph.D., University of Heidelberg
	B.S., University of Zagreb
	Postdoctoral Research, Harvard Medical School/Massachussetts General Hospital

The main research interest of my laboratory is in understanding the mechanisms of cancer metastasis via the lymphatic system and the function of lymphatic vessels in the regulation of immune response.

Metastasis is the main cause of treatment failure and death for cancer patients. The first site to which cancer cells metastasize are lymph nodes, and the extent of lymph node involvement is a major criterion for evaluating patient prognosis and the choice of therapy. Despite the fact that the importance of the lymphatic system as a pathway for cancer metastasis has been well recognized, research efforts over the past decades have been focused primarily on understanding the mechanisms of tumor spread via the blood vasculature. Thus, the mechanisms of tumor spread via the lymphatic system remain poorly understood. Aside from serving as a transport system for tumor cells, the lymphatic system normally collects extravasated fluid, macromolecules and leukocytes from tissues and returns them to the blood circulation. By directing antigen-presenting cells, T-cells and antigens from peripheral tissues into the lymph nodes, lymphatic vessels play an important role in the initiation of immune response. However, the mechanisms by which leukocytes are mobilized into the lymphatic vessels are poorly understood, and in particular, the role of lymphatic vessels in the process remains unknown.

Our long-term research efforts are dedicated towards elucidating the molecular mechanisms which regulate lymphatic vessel growth (i.e. lymphangiogenesis) and the function of lymphatic vessels in cancer and in normal physiology. Current research includes investigations of the mechanisms by which tumor cells interact with the lymphatic vasculature during early steps of metastasis. We are investigating the role of role of chemokines and cell adhesion molecules expressed by the lymphatic endothelium in tumor invasion and metastasis, to gain insight into the mechanisms which regulate tumor cell migration and entry into the lymphatic vessels. We are also investigating the molecular mechanisms of lymphangiogenesis. Our previous studies have demonstrated that the induction of tumor lymphangiogenesis by the Vascular Endothelial Growth Factor-C (VEGF-C) facilitates tumor metastases. The goals of our current research activities are to better understand the mechanisms by which VEGF-C promotes metastasis and to assess the potential of VEGF-C and its receptors as targets for the anti-metastatic therapy. Our efforts are also dedicated towards identification of novel lymphangiogenic factors and markers of the lymphatic endothelium. Finally, the lab is exploring the role of lymphatic vasculature in the regulation of immune response, particularly its function in regulating migration and activation of antigen-presenting cells. The ultimate goal of these studies is to gain insight into the molecular mechanisms by which lymphatic endothelial cells control physiological cell migration and to examine whether tumor cells take advantage of these mechanisms to gain access to the lymphatic vessels. The knowledge gained with the above studies may provide a foundation for the development of new therapeutic approaches to predict, arrest and treat cancer metastases.

Graduate Students
Simona Podgrabinska, Bryan Kloos

Postdoctoral Fellows
Suvendu Das, Xiaodong Zhang

Clinical Research Fellow
Konstantin Zakashansky

Research Associate
Jeremy Medalle

Skobe M, Rockwell P, Goldstein N, Vosseler S, Fusenig NE. Halting angiogenesis suppresses carcinoma cell invasion. Nat Med. 1997 Nov; 3(11): 1222-7.

Skobe M, Fusenig NE. Tumorigenic conversion of immortal human keratinocytes through stromal cell activation. Proc Natl Acad Sci U S A. 1998 Feb; 95(3): 1050-5.

Skobe M, Detmar M. Structure, function, and molecular control of the skin lymphatic system. J Investig Dermatol Symp Proc. 2000 Dec; 14(9): 14-9.

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. Nat Med. 2001 Feb; 7(2): 192-8.

Skobe M, Hamberg LM, Hawighorst T, Schirner M, Wolf GL, Alitalo J, Detmar M. Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage recruitment by vascular endothelial growth factor-C in melanoma. Am J Pathol. 2001 Sep; 153(3): 893-903.

Cassella M, Skobe M. Lymphatic vessel activation in cancer. Ann NY Acad Sci 2002 Dec; 979: 120-30.

Podgrabinska S, Braun P, Velasco P, Kloos B, Pepper MS, Skobe M. Molecular characterization of lymphatic endothelial cells. Proc Natl Acad Sci U S A. 2003 Apr; 100(8): 4970.

Pepper MS, Tille JC, Nisato R, Skobe M. Lymphangiogenesis and tumor metastasis. Cell Tissue Res. 2003 Oct; 314(1): 167-77.

Pepper MS, Skobe M. Lymphatic endothelium: morphological, molecular and functional properties. J Cell Biol. 2003 Oct; 163(2): 209-13.

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 Res 2006 Mar 1; 66(5): 2650-7.