The candidate, Dr. Diane Bielenberg, is an instructor in the Surgical Research Division at Children's Hospital and Harvard Medical School, chaired by Dr. Judah Folkman, the pioneer of the field of angiogenesis research. As part of the Vascular Biology Program, Dr. Bielenberg, a cancer biologist, has specialized in studies of metastasis, the spread of malignant tumor cells from one site in the body to another. The longterm career goals of the applicant are to remain in academic research and continue to study the biology of cancer metastasis and angiogenesis. Most cancer patients die from metastasis, and only by understanding the biology of this process can we hope to develop better tools to fight this disease. Dr. Bielenberg has previously studied the molecular mechanisms involved in anti-angiogenesis therapy by interferons, the role of endogenous interferon-beta in the involution of cutaneous infantile hemangiomas, and the identification and anti-tumor activity of a natural soluble receptor for vascular endothelial growth factor called soluble neuropilin. Since being promoted to an instructor, Dr. Bielenberg has focused on a novel suppressor of metastasis, called Semaphorin 3F. Semaphorin 3F is commonly deleted in lung cancer and is a putative tumor suppressor gene, but recently Dr. Bielenberg and her mentor, Dr. Michael Klagsbrun, have shown that Semaphorin 3F is inversely correlated with metastasis in many tumor cell lines. When Semaphorin 3F was expressed in metastatic cells, the tumors remarkably reverted to a benign, hypo-vascular and encapsulated tumor phenotype. This K01 research proposal will follow-up this exciting finding and focus on the molecular mechanisms responsible for the anti-metastatic effect of Semaphorin 3F. We hypothesize that Semaphorin 3F will regulate key steps in the metastatic cascade including angiogenesis and lymphangiogenesis and may offer a novel therapeutic strategy for patients with metastatic disease. A K01 award would facilitate the transition of this candidate from instructor to an independent investigator in the Department of Surgical Research at Harvard Medical School by providing additional training in areas of biochemistry including protein engineering and protein purification, as well as enabling additional collaborations and participation in regional and national meetings. Most of all, a Howard Temin Award would enable the continuation of this research project toward the ultimate goal of long-term stable disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA118732-04
Application #
7640865
Study Section
Special Emphasis Panel (ZCA1-RTRB-A (M1))
Program Officer
Lohrey, Nancy
Project Start
2006-07-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
4
Fiscal Year
2009
Total Cost
$159,300
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Mucka, Patrick; Levonyak, Nicholas; Geretti, Elena et al. (2016) Inflammation and Lymphedema Are Exacerbated and Prolonged by Neuropilin 2 Deficiency. Am J Pathol 186:2803-2812
Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana et al. (2016) Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma. Am J Pathol 186:1055-64
Banyard, Jacqueline; Bielenberg, Diane R (2015) The role of EMT and MET in cancer dissemination. Connect Tissue Res 56:403-13
Migliozzi, Matthew T; Mucka, Patrick; Bielenberg, Diane R (2014) Lymphangiogenesis and metastasis--a closer look at the neuropilin/semaphorin3 axis. Microvasc Res 96:68-76
Panigrahy, Dipak; Adini, Irit; Mamluk, Roni et al. (2014) Regulation of soluble neuropilin 1, an endogenous angiogenesis inhibitor, in liver development and regeneration. Pathology 46:416-23
Banyard, Jacqueline; Chung, Ivy; Migliozzi, Matthew et al. (2014) Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer. BMC Cancer 14:387
Shahrabi-Farahani, Shokoufeh; Wang, Lili; Zwaans, Bernadette M M et al. (2014) Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas. Lab Invest 94:752-65
Coughlin, Mark F; Bielenberg, Diane R; Lenormand, Guillaume et al. (2013) Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with different metastatic potential. Clin Exp Metastasis 30:237-50
Banyard, Jacqueline; Chung, Ivy; Wilson, Arianne M et al. (2013) Regulation of epithelial plasticity by miR-424 and miR-200 in a new prostate cancer metastasis model. Sci Rep 3:3151
Bielenberg, Diane R; Seth, Abhishek; Shimizu, Akio et al. (2012) Increased smooth muscle contractility in mice deficient for neuropilin 2. Am J Pathol 181:548-59

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