DEPARTMENT OF PATHOLOGY

Judith A. Varner, Ph.D.

Judith A. Varner, Ph.D.

  • Professor
  • A.B. - Chemistry, Duke University, Durham, NC
  • Fulbright Fellowship - University of Basel, Basel, Switzerland
  • Ph.D. - University of Basel, Basel, Switzerland
  • Postdoctoral Fellow - Dept. Molecular Genetics, Tampa Bay Research Institute
  • Postdoctoral Fellow - Dept. Pharmacology, University of North Carolina, Chapel Hill

Research Interests

The research in my lab focuses principally on identifying the molecular mechanisms by which normal cells in the tumor microenvironment contribute to tumor growth and spread. We have published extensively on molecular mechanisms regulating tumor angiogenesis and lymphangiogenesis. Our work in recent times has turned to focus on the role of innate immune cells, including granulocytes, monocytes, macrophages and so-called myeloid derived suppressor cells in the regulation of tumor growth and angiogenesis. We recently described a key role for PI3Kinase gamma in the regulation of monocyte trafficking to tumors and their subsequent promotion of tumor growth and metastasis. We found that tumor derived growth factors, cytokines and chemokines activate integrin a4b1 to promote myeloid cell adhesion to vascular endothelium in tumors. This activation event requires a series of steps leading to conformational changes in integrin a4b1 and depend on PI3kinase gamma activation of the small GTPase Rap1. We furthermore are characterizing the regulation of the M1 vs M2 macrophage phenotype by PI3kinase gamma and studying the role of macrophages in tumor angiogenesis, lymphangiogenesis and fibrosis.

Representative Publications

  1. Schmid MC, Avraamides CJ, Dippold HC, Franco I, Philippe Foubert P, Ellies LG, Acevedo LM, Manglicmot JRE, Song X, Wrasidlo W,Blair SL, Ginsberg MH, Cheresh DA, Hirsch E, Field SJ, and Varner JA (2011) Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3Kg, a single convergent point promoting tumor inflammation and progression, Cancer Cell 19, 715-727
  2. Garmy-Susini B, Avraamides CJ, Schmid MC, Foubert P, Ellies LG, Barnes L, Feral C, Papayannopoulou T, Lowy A, Blair SL, Cheresh D, Ginsberg M, Varner JA (2010). Integrin alpha4beta1 signaling is required for lymphangiogenesis and tumor metastasis. Cancer Res. 70:3042-51.
  3. Jin H, Garmy-Susini B, Avraamides CJ, Stoletov K, Klemke RL, Varner JA. (2010) A PKA-Csk-pp60Src signaling pathway regulates the switch between endothelial cell invasion and cell-cell adhesion during vascular sprouting. Blood. 116:5773-83.
  4. Avraamides, C.J., Garmy-Susini, B. and Varner J.A. (2008) Integrins in Angiogenesis and LymphangiogenesisNature Reviews Cancer 8: 604-617.
  5. Jin, H., Aiyer A., Su J., Borgstrom, P., Stupack, D., Friedlander, M. and Varner, J (2006) “A homing mechanism for bone marrow derived progenitor cell recruitment to the neovasculature”, J. Clin. Invest. 116: 652-662. 
  6. Garmy-Susini, B., Jin, H., Zhu, Y., Sung, R.-J., Hwang, R. and Varner, J. (2005) Integrin a4b1-VCAM mediated adhesion between endothelial and mural cells is required for blood vessel maturation.” J. Clin. Invest. 115, 1542-1551.
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Biography

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