Associate Professor
Scientist
Ph.D., UCLA
Phone: 631-344-8041
Lpena@bnl.gov
Medical Department
Brookhaven National Laboratory
The Peña Lab
Research
Our laboratory investigates cellular and molecular mechanisms of radiation sensitivity. Ionizing radiation can induce cells to undergo programmed cell death (apoptosis), independent of DNA damage. Toxic effects are mediated by stress signal transduction, such as the JNK/SAPK pathway, and antagonized by AKT/PKB and ERK pathways. Our goal is to exploit these pathways to protect normal cells and, conversely, sensitize tumor cells. A major focus is on non-neuronal cells of the CNS. This includes normal microvessel endothelial cells and glial cells such as oligodendrocytes. The former comprise capillaries and the blood brain barrier, and the latter produce the myelin and white matter of the CNS. Injury to these cells by therapeutic radiation can result in white matter necrosis and debilitating neurological deficits in patients. We have demonstrated in cell culture and in animal models that the heparin-binding cytokine bFGF, cuts the level of acute radiation-induced apoptosis in half in endothelial cells and oligodendrocytes. We are currently studying whether late effect radiaiton injury can also be reduced. Recently, we have developed a series of synthetic analogs of bFGF, and are employing them in these and other models of CNS injury. These multi-domain peptide analogs are modular in design, and one the modules is being exploited to target cytokine / growth factor receptors as an imaging agent. When a positron emitting radionuclide (18-fluorine or 124-iodine) is attached to the bFGF receptor-targeting module, for example, we can image by PET (Positron Emission Tomography) the expression of FGF Receptors in disease states where these cytokine / growth factors are upregulated. The experimental CNS models we are currently employing for this purpose are the EAE and LPC animal models of Multiple Sclerosis. In theory, this strategy can be applied to many cytokine / growth factor receptor systems in addition to the FGFs.
- Publications
- Laboratory Personnel
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- Lin X., Takahashi K., Campion S.L., Liu Y., Gustavsen G.G., Peña L.A. and Zamora P.O.: Synthetic peptide F2A4-K-NS mimics FGF-2 in vitro and is angiogenic in vivo. Int J Mol Med (In Press), 2006.
- Lin X., Zamora P.O., Albright S., Glass J.D. and Peña L.A.: Multidomain synthetic peptide B2A2 synergistically enhances BMP-2 in vitro. J Bone Miner Res 20:693-703, 2005. (PubMed Abstract)
- Zamora P.O., Tsang R., Peña L.A., Osaki S. and Som P.: Local delivery of basic fibroblast growth factor (bFGF) using adsorbed silyl-heparin, benzyl-bis(dimethylsilylmethyl)oxycarbamoyl-heparin. Bioconjug Chem 13:920-926, 2002. (PubMed Abstract)
- Dilmanian F.A., Button T.M., Le Duc G., Zhong N., Peña L.A., et al.: Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy. Neuro-oncol 4:26-38, 2002. (PubMed Abstract)
- Peña L.A., Fuks Z. and Kolesnick R.N.: Radiation-induced apoptosis of endothelial cells in the murine CNS: Protection by fibroblast growth factor and sphingomyelinase deficiency. Cancer Res 60:321-327, 2000. (PubMed Abstract)
- Separovic D., Pink J.J., Oleinick N.A., Kester M., Boothman D.A., McLoughlin M., Peña L.A. and Haimovitz-Friedman A.: Niemann-Pick human lymphoblasts are resistant to phthalocyanine 4-photodynamic therapy-induced apoptosis. Biochem Biophys Res Commun 258:506-512, 1999. (PubMed Abstract)
- Mathias S., Peña L.A. and Kolesnick R.N.: Signal transduction of stress via ceramide. Biochem J 335:465-480, 1998. (PubMed Abstract)
- Peña L.A., Fuks Z. and Kolesnick R.N.: Stress-induced apoptosis and the sphingomyelin pathway. Biochem Pharmacol 53:615-621, 1997. (PubMed Abstract)
- Santana P., Peña L.A., Haimovitz-Friedman A., Martin S., Green D., McLaughlin M., Cordon-Cardo C., Schuchman E.H., Fuks Z. and Kolesnick R.N.: Acid sphingomyelinase deficient human lymphoblasts and mice are defective in radiation-induced apoptosis. Cell 86:189-199, 1996. (PubMed Abstract)
- Peña L.A., Brecher C.W. and Marshak D.R.: beta-Amyloid regulates gene expression of glial trophic substance S100 beta in C6 glioma and primary astrocyte cultures. Mol Brain Res 34:118-126, 1995. (PubMed Abstract)
- Zhong Y. and Peña L.A.: A novel synaptic transmission mediated by a PACAP-like neuropeptide in Drosophila. Neuron 14:527-536, 1995. (PubMed Abstract)
- Kumar S., Peña L.A. and de Vellis J.: CNS glial cells express neurotrophin receptors whose levels are regulated by NGF. Brain Res Mol Brain Res 17:163-168, 1993. (PubMed Abstract)
- Kumar S., Huber J., Peña L.A., Perez-Polo J.R., Werrbach-Perez K. and de Vellis J.: Characterization of functional nerve growth factor-receptors in a CNS glial cell line: monoclonal antibody 217c recognizes the nerve growth factor-receptor on C6 glioma cells. J Neurosci Res 27:408-417, 1990. (PubMed Abstract)