Robert W. Wysocki

Robert W. Wysocki
B.A. Hamilton College, 2007

8th Year MSTP
4th Year Med SchoolImage: Robert W. Wysocki

Advisor: Mikala Egeblad, PhD

Cold Spring Harbor Laboratory

Graduate Program: Genetics

Title:  Neutrophil Extracellular Traps (NETs) are induced by breast cancer cells to promote lung metastasis 

Abstract (rotation):

Vascular endothelial growth factor (VEGF) promotes tumor angiogenesis and leads to increased vascular permeability. It has been proposed that anti-VEGF treatment decreases vascular leakage, improving penetration of chemotherapeutics into tumors. Bevacizumab is approved in combination with chemotherapy for treating advanced cancer. However, bevacizumab has serious adverse effects and resistance is common. FDA recently withdrew approval for bevacizumab for advanced breast cancer because effects on survival were small relative to the serious side effects. Recent data suggested that bevacizumab provides a better response in triple-negative breast cancer. Confounding the debate about the mechanisms of action and response to ant-VEGF treatment is the lack of in vivo studies determining the acute and chronic effects of bevacizumab treatment in conjunction with standard chemotherapy.

Using mouse models of different subtypes of breast cancer combined with intravital imaging of tumors, we have begun to characterize the vascular changes and effect on response to chemotherapy resulting from treatment with a murine anti-VEGF antibody (B20-4.1.1; kindly provided by Genentech). This study will shed light on the mechanism of action of anti-VEGF antibody treatment and help to inform future clinical trials using this agent.

Publications:
(pre-MSTP publications indicated with an *)

Park, J*, RW Wysocki*, Z Amoozgar*, L Maiorino*, MR Fein, J Jorns, AF Schott, Y Kinugasa-Katayama, Y Lee, NH Won, ES Nakasone, SA Hearn, Victoria Kuettner, J Qiu, AS Almeida, N Perurena, K Kessenbrock, MS Goldberg, and M Egeblad. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. (under review at Science Translational Medicine as of 8/3/16)

Knight ZA, Tan K, Birsoy K, Schmidt S, Garrison JL, Wysocki RW, Emiliano A, Ekstrand MI, Friedman JM. (2012). Molecular profiling of activated neurons by phosphorylated ribsome capture. Cell. Nov; 151(5):1126-1137.

*Pérez CA, Stanley SA, Wysocki RW, Havranova J, Ahrens-Nicklas R, Onyimba F, Friedman JM. (2011). Molecular annotation of integrative feeding neural circuits. Cell Metab. Feb; 13(2):222-232.

*Hedbacker K, Birsoy K, Wysocki RW, Asilmaz E, Ahima RS, Farooqi IS, Friedman JM. (2010). Antidiabetic effects of IGFBP2, a leptin-regulated gene. Cell Metab. Jan.; 11(1):11-22.