Our Science – Bianco Website

Caterina Bianco, M.D., Ph.D.

Mammary Biology and Tumorigenesis Laboratory Tumor Growth Factor Section Staff Scientist 37 Convent Drive Bldg 37 Room 1112 Bethesda, MD 20892 Phone:   301-4513761 Fax:   301-4028656 E-Mail:   biancoc@mail.nih.gov

Biography

Dr. Bianco received her M.D. from University of Naples Federico II, Italy, in 1991 and her Ph.D. in Genetic Disease and Gene Therapy from University G. D Annunzio, Chieti, Italy, in 2003. Following an oncology residency program at the University of Naples Federico II Medical School, she joined the Tumor Growth Factor Section of MBTL at the NCI in 1996 as a postdoctoral fellow and in 2001 she became a Staff Scientist.

Research

My research program focuses on the study of Cripto-1 and its relationship to the pathogenesis of human cancer. My current goals are:

1. Delineate the biological activity and intracellular molecular signaling pathways by which Cripto-1 can modify mammary and colonic epithelial differentiation and transformation.
We have identified and characterized two novel receptors that are activated by Cripto-1 and that induce activation of two different intracellular signaling pathways. Screening a human brain phage display library using Cripto-1 recombinant protein as bait, we have cloned the serine threonine kinase receptor ALK4 (ACTRIB) as a receptor for Cripto-1. Binding of Cripto-1 to ALK4 in the presence of the TGFβ-related molecule, Nodal, induces activation of a canonical Smad2 and Smad3 signaling pathway. In addition to activating a Smad signaling pathway, Cripto-1 can signal in mammalian cells independently from Nodal leading to activation of intracellular signaling pathways that regulate cell proliferation, cell motility and survival through both ras/raf/MAPK and PI3-K/AKT. In particular, activation of these two signaling pathways is mediated by direct binding of Cripto-1 to the GPI-linked heparan sulphate proteoglycan Glypican-1, which can then activate the cytoplasmic tyrosine kinase c-src.

2. Assess Cripto-1 role in tumor angiogenesis.
Our laboratory has been the first to demonstrate that Cripto-1 can stimulate angiogenesis in vitro and in vivo and that this angiogenic activity of Cripto-1 can be strongly inhibited by a blocking anti Cripto-1 monoclonal antibody.

3. Validate Cripto-1 role as a cancer biomarker.
We have developed a specific and sensitive sandwich-type Enzyme-Linked Immunosorbent Assay (ELISA) for detection of Cripto-1 in biological fluids such as human milk and plasma from cancer patients. Using this ELISA we have determined Cripto-1 plasma levels in patients with colon and breast carcinomas and we have shown that Cripto-1 plasma levels are significantly higher in the plasma of colon and breast cancer patients as compared to a control group of healthy subjects. We are currently coordinating the optimization of this sandwich ELISA for Cripto-1 for preclinical evaluation of this assay in a large number of cancer patients.

This page was last updated on 7/14/2008.