Gabriele Bergers PhD
Professor of Neurological Surgery
Neill H. and Linda S. Brownstein Endowed Chair in Brain Tumor Research
Principal Investigator, Brain Tumor Research Center
Faculty Member, Biomedical Sciences Graduate Program (http://www.ucsf.edu/bms/)
Dr. Bergers’ research focuses on revealing the dialogue between the tumor cell compartment and the vascular niche, a microanatomical unit of which the vasculature is an integral component. The vascular niche consists of distinct cell types and specialized matrices that provide signals controlling stem cell proliferation, fate specification, and protection in not only normal tissue, but tumors, as well. Importantly, the vascular niche in tumors is aberrant compared to the vascular niche in normal tissues, since the tumor vasculature is hyperproliferative and abnormal in both structure and function. Moreover, it harbors various distinct inflammatory cells, including bone marrow-derived immune cells, which have been implicated in neovascularization and therapy resistance. Her lab studies the vascular niche primarily in glioblastoma multiforme (GBM), the most aggressive and prevalent brain tumor in adults, characterized by rapid and invasive growth, with patients having an overall median survival of only one year. GBM are also one of the most vascularized tumors due to their high expression levels of vascular endothelial growth factor (VEGF/VPF). The brain environment is unique in that it contains specialized cells, a matrix distinct from other organs, and a blood-brain barrier (BBB) that are collectively affected during tumorigenesis, opening up new avenues to explore the impact of microenvironmental changes on tumor progression and resistance. To generalize their findings on the tumor-host dialogue in GBM, the Bergers laboratory also performs studies in pancreatic and breast cancer models.
The Bergers laboratory has made critical discoveries elucidating the interactions among tumor cells and the blood vessels and inflammatory cells of the vascular niche in regulating neovascularization and invasion in various transgenic and orthotopic mouse models of cancer. Dr. Bergers’ group has also made strides in revealing and understanding the adaptation mechanisms of tumors, including GBM, during the course of antiangiogenic therapy blocking the VEGFR pathway.
Dr. Bergers has received several awards for her research, including the prestigious Sidney Kimmel and Sandler Opportunity Awards, and has been a member of numerous advisory boards. She has served as an External Advisory Board member for various universities and pharmaceutical companies, including Amgen and Pfizer, and is currently on the Editorial Board of Cancer Research and Science. She has been serving on the NIH Tumor Microenvironment Study Section since 2006 and became Chair in 2010. In addition, Dr. Bergers is the co-director of the TMEN (Tumor Microenvironment) Brain Tumor center at UCSF , a member of the NIH TMEN workgroup, as well as an EAB member at the Max-Planck-Institute for Biomedicine (Vascular Biology focus) in Muenster, Germany. She is also a member of the Rosalind Franklin Society.
Education, Training, and Previous Positions
- 1988: BS, University of Munich (LMU), Munich, Germany
1989: Diploma Thesis, University of Munich and Max-Planck Institute of Biochemistry, Martinsried, Germany
1993: PhD, Institute of Molecular Pathology (IMP) and University of Vienna, Austria
1994-1997: Postdoctoral Fellow, Department of Biochemistry & Biophysics, UCSF
Selected Professional Memberships and Appointments
- American Association for Cancer Research
UCSF Cancer Center
UCSF Program for Mouse Models of Human Cancer
Rosalind Franklin Society
Selected Honors and Awards
- 1989-1989: Max-Planck diploma student fellowship
1989-1993: Ph.D. student fellowship of the IMP
1994-1995: DAAD - NATO fellowship
1995-1996: Postdoctoral Fellowship: "Deutscher Akademischer Austauschdienst"
2002-2004: Sydney Kimmel Scholar Award
2003-2005: V Foundation Scholar Award
Selected Recent Publications
Lu KV, Chang JP, Parachoniak CA, Pandika MM, Aghi MK, Meyronet D, Isachenko N, Fouse SD, Phillips JJ, Cheresh DA, Park M, Bergers G. VEGF Inhibits Tumor Cell Invasion and Mesenchymal Transition through a MET/VEGFR2 Complex. Cancer Cell 2012;22(1):21-35. Cited by: Claesson-Welsh L. Receptor talk and tumor cell walk in glioblastoma. Cancer Cell 2012;22(1):1-2.
Dvorak HF, Weaver VM, Tlsty TD, Bergers G. Tumor microenvironment and progression. J Surg Oncol 2011;103(6):468-74.
Persson AI, Petritsch C, Swartling FJ, Itsara M, Sim FJ, Auvergne R, Goldenberg DD, Vandenberg SR, Nguyen KN, Yakovenko S, Ayers-Ringler J, Nishiyama A, Stallcup WB, Berger MS, Bergers G, McKnight TR, Goldman SA, Weiss WA. Non-stem cell origin for oligodendroglioma. Cancer Cell 2010;18(6):669-82.
Lu KV, Zhu S, Cvrljevic A, Huang TT, Sarkaria S, Ahkavan D, Dang J, Dinca EB, Plaisier SB, Oderberg I, Lee Y, Chen Z, Caldwell JS, Xie Y, Loo JA, Seligson D, Chakravari A, Lee FY, Weinmann R, Cloughesy TF, Nelson SF, Bergers G, Graeber T, Furnari FB, James CD, Cavenee WK, Johns TG, Mischel PS. Fyn and SRC are effectors of oncogenic epidermal growth factor receptor signaling in glioblastoma patients. Cancer Res 2009;69(17):6889-98.
Pàez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Viñals F, Inoue M, Bergers G, Hanahan D, Casanovas O. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009;15(3):220-31.
Lu K, Lamagna C, Bergers G. Chapter 3. Bone marrow-derived vascular progenitors and proangiogenic monocytes in tumors Methods Enzymol 2008;445:53-82.
Bergers G, Hanahan D. Modes of resistance to anti-angiogenic therapy [Review]. Nat Rev Cancer 2008;8(8):592-603.
Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, Vandenberg SR, Ginzinger DG, James CD, Costello JF, Bergers G, Weiss WA, Alvarez-Buylla A, Hodgson JG. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med 2008;6:14.
Du R, Lu KV, Petritsch C, Liu P, Ganss R, Passegué E, Song H, Vandenberg S, Johnson RS, Werb Z, Bergers G. HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 2008;13(3):206-20.
Du R, Petritsch C, Lu K, Liu P, Haller A, Ganss R, Song H, Vandenberg S, Bergers G. Matrix metalloproteinase-2 regulates vascular patterning and growth affecting tumor cell survival and invasion in GBM. Neuro Oncol 2008;10(3):254-64.
Pietras K, Pahler J, Bergers G, Hanahan D. Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting. PLoS Med 2008;5(1):e19.
Chesler L, Goldenberg DD, Seales IT, Satchi-Fainaro R, Grimmer M, Collins R, Struett C, Nguyen KN, Kim G, Tihan T, Bao Y, Brekken RA, Bergers G, Folkman J, Weiss WA. Malignant progression and blockade of angiogenesis in a murine transgenic model of neuroblastoma. Cancer Res 2007;67(19):9435-42.
Blouw B, Haase VH, Song H, Bergers G, Johnson RS. Loss of vascular endothelial growth factor expression reduces vascularization, but not growth, of tumors lacking the Von Hippel-Lindau tumor suppressor gene. Oncogene 2007;26(31):4531-40.
Kawaguchi T, Yamashita Y, Kanamori M, Endersby R, Bankiewicz KS, Baker SJ, Bergers G, Pieper RO. The PTEN/Akt pathway dictates the direct alphaVbeta3-dependent growth-inhibitory action of an active fragment of tumstatin in glioma cells in vitro and in vivo. Cancer Res 2006;66(23):11331-40.
Lamagna C, Bergers G. The bone marrow constitutes a reservoir of pericyte progenitors. J Leukoc Biol. 2006;80(4):677-81.
Holash J, Thurston G, Rudge JS, Yancopoulos GD, Adjei AA, Bergers G, Pytowski B, Pegram M, Gordon MS. Inhibitors of growth factor receptors, signaling pathways and angiogenesis as therapeutic molecular agents. Cancer Metastasis Rev 2006;25(2):243-52.
Casanovas O, Hicklin DJ, Bergers G, Hanahan D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 2005;8(4):299-309.
Bergers G, Song S. The role of pericytes in blood-vessel formation and maintenance [Review]. Neuro Oncol 2005;7(4):452-64.
Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G. PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 2005;7(9):870-9.
Berger M, Bergers G, Arnold B, Hämmerling GJ, Ganss R. Regulator of G-protein signaling-5 induction in pericytes coincides with active vessel remodeling during neovascularization. Blood 2005;105(3):1094-101.