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Research Overview

The Bielenberg laboratory is interested in cancer biology and the study of metastasis.

Metastasis, the spread of cancer cells to distant sites, is the most common cause of death in cancer patients. There are two main routes by which tumor cells disseminate, through blood vessels and through lymphatic vessels. As tumors grow in size their requirements for nutrients and oxygen (carried in blood) increases. To obtain these necessities, tumor cells induce new blood vessels to sprout into the tumor environment, a process called angiogenesis. Besides providing nutrients, tumor blood vessels also serve as an escape route for tumor cells. Therefore, therapies aimed at inhibiting angiogenesis should not only block tumor growth but also metastasis. Tumor blood vessels are leaky and

lead to increased fluid volume and pressure in the interstitial space. Peri-tumoral lymphatic vessels often grow in size to compensate and drain this increased fluid and sometimes sprout into the tumor. Tumor-associated lymphatic capillaries can increase 10-50 times in diameter. These enlarged lymphatic vessels serve as the primary escape route for tumor cells, and indeed, sentinel lymph node metastases are often the first sign of malignancy. The lymphatic system returns fluid back to the blood vascular system through the thoracic duct, therefore tumor cells exiting through lymphatic vessels can spread throughout the body. Therapies aimed at inhibiting lymphangiogenesis are being explored in the Bielenberg laboratory.

The Bielenberg laboratory is pursuing several projects related to the topic of metastasis and the inhibition of tumor angiogenesis and lymphangiogenesis. Specifically, these include:

  • Examining the effect of Semaphorin 3F, a ligand of Neuropilin 2, on tumor growth, angiogenesis, lymphangiogenesis, and metastasis.
  • Determining the effects of low-dose chemotherapy on tumor-associated lymphangiogenesis.
  • Investigating the expression and regulation of Neuropilin 2, a receptor expressed on blood vessels and lymphatic vessels, in (lymph)angiogenesis models using transgenic mice.
  • Examining the expression, function, and role in metastasis of VEGF receptors including VEGFR2 and Neuropilins in tumor cells.
  • Establishing new tumor model systems to investigate the process of metastasis in breast, prostate, and ovarian cancers.

Research Background

Diane Renee Bielenberg received a BS in Chemistry and Biology from the University of Northern Iowa and a PhD in Cancer Biology from the University of Texas Health Science Center and MD Anderson Cancer Center. Dr. Bielenberg performed her post-doctoral studies as an American Cancer Society Fellow at Harvard Medical School and Children's Hospital. She joined the Vascular Biology Program as an Assistant Professor in 2005. Dr. Bielenberg has received several research grant awards including the Howard Temin Award from the NCI, the Dr. Patricia Wexler Award from the Skin Cancer Foundation, and the Patterson Trust Award. In 2008, Dr. Bielenberg received the Harvard Medical School Young Mentor Award.

Selected Publications

  1. Gagnon ML*, Bielenberg DR*, Gechtman Z, Miao H, Takashima S, Soker S, Klagsbrun M. (2000) Identification of a Natural Soluble Neuropilin-1 that Binds Vascular Endothelial Growth Factor: In Vivo Expression and Anti-tumor Activity. Proc Natl Acad Sci USA, 97(6): 2573-2578. *Both authors contributed equally to the manuscript.
  2. Bielenberg DR, Hida Y, Shimizu A, Kaipainen A, Kreuter M, Kim CC, Klagsbrun M. (2004) Semaphorin 3F, a Chemorepulsant for Endothelial Cells, Induces a Poorly Vascularized, Encapsulated, Nonmetastatic Tumor Phenotype. Journal of Clinical Investigation, 114(9): 1260-1271. Commentary in: Hutchinson, E. (2004). Metastasis - No way out? Nature Reviews Cancer, 4: 921.
  3. Mamluk R, Detmar M, Klagsbrun M, Bielenberg D. (2005) Soluble Neuropilin Targeted to the Skin Inhibits Vascular Permeability. Angiogenesis, 8(3): 217-227.
  4. Bielenberg DR, Pettaway CA, Takashima S, Klagsbrun M. (2006) Neuropilins in Neoplasms; Expression, Regulation, and Function. Experimental Cell Research, 312(5): 584-93.
  5. Bielenberg DR, Klagsbrun M. (2007) Targeting Endothelial and Tumor Cells with Semaphorins. Cancer Metastasis Reviews, 26(3-4): 421-431.
  6. Zwaans BMM, Bielenberg DR. (2007) Potential Therapeutic Strategies for Lymphatic Metastasis. Microvascular Research, 74(2-3): 145-58.

Publications