Dr. Kitajewski obtained his PhD from Princeton University and postdoctoral training at UCSF before joining the Columbia University faculty. His research interests are in developmental and pathological angiogenesis, with a focus on embryonic blood and lymphatic vessel development, reproductive angiogenesis and tumor angiogenesis in breast and ovarian cancer. The lab explores the Notch signaling cascade and has determined how cell-fate determination mediated by Notch and VEGF guides the proper construction of the vasculature. Notch is critical for endothelial cell differentiation, vascular remodeling, arterial/venous specification, sprouting angiogenesis, lumen formation and vessel maturation. The efforts to uncover signaling cascades that regulate or promote angiogenesis have established roles for Wnt/Frizzled in sprouting angiogenesis, NF-Kappa signaling in endothelial homeostasis, CLIC chloride channels in angiogenesis, and the Anthrax Toxin Receptors in extracellular matrix homeostasis. In addition, Notch functions in pathological angiogenesis and the Kitajewski lab has developed Notch inhibitors that have been used to define the role of Notch in tumor angiogenesis, lymphangiogenesis and the inflammatory response. These Notch antagonists have utility in blocking tumor growth in animal models by reducing tumor angiogenesis and restricting blood flow to tumors.
Butler JM, Nolan DJ, Vertes EL, Varnum-Finney B, Kobayashi H, Hooper AT, Seandel M, Shido K,White IA, Kobayashi M, Witte L, May C, Shawber C, Kimura Y, Kitajewski J, Rosenwaks Z, Bernstein ID, Rafii S.
Endothelial cells are essential for the self-renewal and repopulation of Notch-dependent hematopoietic stem cells. Cell Stem Cell 6:251-64. (2010)
Outtz HH, Wu JK, Wang X, Kitajewski J.
Notch1 Deficiency Results in Decreased Inflammation during Wound Healing and Regulates VEGFR-1 and Inflammatory Cytokine Expression in Macrophages. J. Immunol. 185:4363-73. (2010)
Reeves C, Young JA, Kitajewski J.
Anthrax Toxin Receptor 2 is expressed in murine vasculature and functions in endothelial proliferation and morphogenesis. Oncogene 29:789-801. (2009)
Funahashi Y, Hernandez S, Das I, Ahn A, Huang J, Vorontchinkhina M, Sharma A, Kanamaru E, Borisenko V, DeSilva DM, Suzuki A, Wang X, Shawber CJ, Kandel JJ, Yamashiro DJ, Kitajewski J.
A Notch1 ectodomain construct inhibits endothelial Notch signaling, tumor growth and angiogenesis. Cancer Research 68:4727-35. (2008)
Shawber CS, Funahashi Y, Francisco E, Podrabinska S, Kitamura Y, Vorontchinkhina M, Shiraishi K, Stowell, S, Chawengsaksophak K, Rossant J, Accili D, Skobe M, Kitajewski J.
Notch signaling alters VEGF responsiveness in blood endothelial cell by directly regulating the expression of VEGFR-3. Journal of Clinical Investigation 117:3369-82. (2007)