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Cell and Cancer Biology Branch

Research

The focus of the Cell and Cancer Biology Branch is the molecular mechanisms involved in solid cancer progression and metastasis. Two areas of emphasis are 1) the investigation of cancer stem cells, i.e. treatment-resistant metastasis-initiating cells, and 2) the interaction of epithelial tumor cells and the microenvironment to promote functions such as angiogenesis that contribute to progression. Within our common areas of interest, the PI's investigate a variety of organ systems including lung, breast, ovarian, and prostate. Strengths of the Branch include the balance of common interests in an integrated area of cancer biology with a diversity of expertise and a mix of investigators with clinical and basic research training. CCBB provides its members with an involved community that brings various perspectives to problems of cancer progression and metastasis. This is complemented by the participation of CCBB PI's in a number of trans-CCR research consortia, which provide a vibrant opportunity for multiple investigators to collaborate and share ideas within narrowly focused areas of research. Brief synopses of research interests are as follows:

Dr. Kelly's interest centers upon the identification and characterization of
signaling pathways that mediate cancer progression and metastasis, with particular attention to pathways that function in prostate cancer metastasis. The laboratory uses two complementary approaches, genetically engineered mouse models and xenograft models, to address mechanistic questions concerning the origin of PC metastasis, metastatic colonization of secondary organs, and therapeutic responses.

Dr. Liu's research interest is to investigate the molecular mechanism of TNF signaling and particularly to study the regulation of TNF-induced apoptotic and necrotic cell death. The research of Dr. Liu's lab is carried out at molecular and cellular levels using genetically modified cells in culture in addition to transgenic/knockout mouse models.

Dr. Niederhuber's lab is investigating the hypothesis that tissue stem cells and early progenitor cells are the cells-of-origin for cancer. Studies in stem cells include: identifying unique stem cell markers; characterizing of niche conditions that influence stem cell maintenance and differentiation; determining whether infection of the tissue stem cell population is necessary for virally mediated carcinogenesis using the viral cancer vector, HPV. A second area of study is that of the complex relationship between tumor cells and the microenvironment, especially the role of TGF-β and its immunologic mediators in tumor progression and metastasis and understanding how normal stroma is changed during tumor progression.

Dr. Linnoila is interested in the pathology and molecular mechanisms of lung carcinogenesis. Her laboratory is investigating neuroendocrine differentiation in normal and neoplastic lung and the contribution of peripheral airway cells to lung carcinogenesis and stem cell microenvironment (niche). The goal of the laboratory is to develop clinically relevant mouse models for human lung cancers.

Dr. Stetler-Stevenson's research focuses on the identification and characterization of metalloproteinase-independent functions of the endogenous proteinase inhibitors known as the tissue inhibitors of metalloproteinases or TIMPs. The laboratory is specifically interested in the TIMP-2-integrin α3β1 signaling pathways that regulate the anti-angiogenic and anti-tumorigenic activities of this endogenous proteinase inhibitor. The laboratory utilizes complementary approaches examining TIMP-2 mediated changes in cell behavior in both in vitro models, as well as xenograft and syngeneic orthotopic tumor models, to address the mechanisms involved in TIMP-2 modulation of the tumor microenvironment resulting in suppression of tumor growth and angiogenesis.

This page was last updated on 11/14/2008.