Our Science – Palena Website
Claudia M. Palena, Ph.D.
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Research
Head, Immunoregulation Group
Dr. Claudia Palena received her Ph.D. degree in Biochemistry from the National University of Rosario, Argentina, in 2000. She subsequently joined the NIH as a Postdoctoral Fellow in the Laboratory of Tumor Immunology and Biology of the National Cancer Institute, and was appointed as a Staff Scientist in 2008 and as a Tenure-Track Investigator in the same laboratory in August 2011. Dr. Palena's current research is focused on the development of novel immunotherapeutic approaches aimed at targeting critical events in tumor progression with the ultimate goal of designing vaccine platforms and combinatorial therapies for the prevention and/or treatment of metastases in human cancer.
Research
The dissemination of solid tumors involves a sequence of events, known as the metastatic cascade, that begins with the detachment of cancer cells from the primary tumor mass, followed by their invasion of surrounding tissues, entrance into circulation, homing in on distant organs, and survival and proliferation at the site of metastasis. One of the goals of our research is to identify and characterize molecules that are essential for the metastatic cascade and that are suitable targets for the development of immunotherapeutic interventions against human cancer. In recent years, it has been demonstrated that the switch of cancer cells from an epithelial to a mesenchymal-like phenotype, via a process designated as epithelial-mesenchymal transition (EMT), is one of the mechanisms that promotes tumor dissemination by enhancing the motility and invasiveness of cancer cells. Our group has identified and characterized the T-box transcription factor, Brachyury, as a driver of EMT in human tumors. We have shown that elevated levels of Brachyury expression in human carcinoma cells induce the epithelial-mesenchymal switch, enhance cell migration and invasiveness, and increase metastatic propensity in xenograft models. Moreover, we demonstrated that Brachyury over-expression in tumor cells associates with resistance to the conventional anti-cancer therapeutics, chemotherapy and radiation.
Our current research is also focused on elucidating the signaling events that induce tumor EMT, which could potentially lead to novel ways to prevent metastasis. We have recently demonstrated that tumor EMT driven by Brachyury over-expression induces the secretion of the chemokine interleukin-8 (IL-8), together with up-regulation of its receptors, and that IL-8 signaling is critical for maintaining the mesenchymal characteristics of human tumor cells. These findings may have implications for cancer therapy as blockade of IL-8 signaling could possibly be a new way to target mesenchymal-like, invasive carcinoma cells, therefore interfering with tumor dissemination and metastasis.
An interesting and distinctive aspect of Brachyury as driver of human tumor EMT is its restrictive expression pattern; Brachyury is predominantly expressed in human carcinomas but only rarely expressed in normal adult tissues. This highly tumor-associated pattern of expression makes Brachyury an appealing target for interventions directed at the EMT process and serves as a model to explore cancer vaccine immunotherapies aimed at directly interfering with tumor progression processes. To this end, we have demonstrated that human Brachyury-specific T cells can be expanded from the blood of cancer patients with a Brachyury-specific 9-mer peptide, and have shown that those T cells are able to lyse various Brachyury-expressing tumor cells.
These studies have been conducted within the framework of collaborations with investigators in the extramural and intramural scientific communities and have led to the current development of Brachyury-based vaccines for the treatment of human carcinomas.
This page was last updated on 4/10/2013.
