Nemenoff Lab

Contacts:

Phone: (303) 724-4833

Email:   raphael.nemenoff@ucdenver.edu

Research Interests

My laboratory is focused on examining molecular pathways that regulate the progression and metastasis of lung cancer.  Lung cancer is the number one cause of cancer deaths, and this is attributable, at least in part to the presence of metastases at the time of diagnosis.  While work over the last 25 years has focused on regulation of oncogenes and tumor suppressor genes in cancer cells, it has become apparent over the last several years that cancer progression and metastasis is a complex process involving interactions between the cancer cells and the tumor microenvironment (TME).  The TME is composed of vascular cells, inflammatory cells, immune cells and fibroblasts.  The goal of our research is to define these interactions and identify important pathways for lung cancer metastasis.  To that end, we have developed a mouse model of lung cancer metastasis in which tumor cells are directly injected into the lungs of mice.  Performing these experiments with mouse tumor cells in syngeneic mice allows us to examine cancer progression in immune competent animals.  In this model, cells form a primary tumor, which over a period of several weeks metastasized to the other lobes of the lung, the mediastinal lymph nodes and distant organs, including the liver and the brain.  A strength of this model is that it allows us to determine the role of specific pathways both in the tumor cells or in the TME by either silencing target genes in the cancer cells or using the appropriate knockout mice.  In addition we have also developed in vitro co-culture systems to examine the molecular crosstalk between cancer cells and stromal cells, including macrophages and vascular cells.  Current projects in the lab are studying the role of eicosanoid production by both tumor cell and macrophages in lung cancer progression, as well as the role of nuclear receptors of the peroxisome proliferators-activated receptor family.

Publications:

1. Nemenoff RA,Meyer AM, Hudich TM, Mozer AB, Snee A, Narumiya S, Stearman RS, Winn RA, Weiser-Evans M, Geraci MW, Keith RL. Prostacyclin prevents murine lung cancer independent of the membrane receptor by activation of PPARg.  2008 Cancer Prevention Res.  1, 349-56. PMID: 19138979

2. Wang X-Q, Li H, Van Putten V, Winn RA, Heasley LE Nemenoff RA. Oncogenic K-Ras Regulates Proliferation and Cell Junctions in Lung Epithelial Cells Through Induction of COX-2 and Activation of MMP-9.  2009. Mol Biol Cell. 20, 791-800.

3. Weiser-Evans MCM, Wang X-Q, Amin J, Van Putten V, Choudhary R, Winn RAM Scheinman R, Simpson P, Nemenoff RA.  Depletion of cytosolic phospholipase A2 in bone marrow-derived macrophages protects against lung cancer progression and metastasis.  2009. Cancer Res. 69: 1733-8. PMID: 19208832.

4. Choudhary R, Li H, Winn RA, Sorenson AL, Weiser-Evans MCM, Nemenoff RA. Peroxisome Proliferator-Activated Receptor-γ(PPAR) Inhibits Transformed Growth of Non-   Small Cell Lung Cancer Cells Through Selective Suppression of Snail.  2010. Neoplasia, in Press.