Louis A. Peña

Director, Nuclear Chemistry Summer School

• For more information on this joint DOE and ACS undergraduate program, see: www.bnl.gov/ncss/

Research Interests

• Radiation Biology
• Neurobiology/Neuro-oncology
• Growth Factor/Cytokine Receptors
• Radiotracer/PET Probe Development
• 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 MAPK/ERK pathways. Our goal is to exploit these pathways develop drugs that protect normal cells or, 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
  (Figure 1) and oligodendrocytes.
• Recently, we have developed a series of synthetic analogs of bFGF. Designated F2A3 and F2A4, these modular, synthetic molecules were shown to stimulate FGF receptors (FGFR1 and FGFR2) in a manner similar to the natural bFGF protein. We are employing them in models of radiation injury as well as applications for wound healing and tissue regeneration (press release). For example, a single dose of bFGF, F2A3, or F2A4 can increase the survival of mice exposed to lethal doses of whole body radiation
  (Figure 2). Further, using the same receptor targeting modules, we are adapting these synthetic molecules to serve as PET imaging probes to visualize cytokine/growth factor receptors in vivo. For example, we are employing experimental animal models of Multiple Sclerosis to create demyelinating lesions in the CNS in which local inflammatory processes and the breakdown of the blood brain barrier result in an over-expression of cytokine receptors. We have been able to visualize FGF receptors in these lesions using a conventional radioisotope
  (Figure 3) and will begin to explore positron-emitting isotopes for PET imaging.

Selected Publications

• Zhang L.R., Sun W.M., Wang J.J., Zhang M., Yang S.M., Tian Y.P., Vidyasagar S., Pena L.A., Zhang K.Z., et al.
  Mitigation effect of an FGF-2 peptide on acute gastrointestinal syndrome after high-dose ionizing radiation.
  Int J Radiat Oncol Biol Phys., 77(1);261-268 (2010).  PubMed
• 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., 17(5):833-839 (2006).  PubMed or Full Text pdf file
• 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(4):693-703 (2005).  PubMed or Full Text pdf file
  
• Chen M., Zamora P.O., Som P., Peña L.A., and Osaki S.
  Cell attachment and biocompatibility of polytetrafluoroethylene (PTFE) treated with glow-discharge plasma of mixed ammonia and oxygen.
  J. Biomater Sci. Polym. Ed., 14(9):917-935 (2003).  PubMed or Full Text pdf file
• 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(5):920-926 (2002).  PubMed or Full Text pdf file
• Dilmanian F.A., Button T.M., Le Duc G., Zhong N., Peña L.A., Smith J.A., Martinez S.R., Bacarian T., Tammam J., Ren B., Farmer P.M., Kalef-Ezra J., Micca P.L., Nawrocky M.M., Niederer J.A., Recksiek F.P., Fuchs A. and Rosen E.M.
  Response of rat intracranial 9L gliosarcoma to microbeam radiation therapy.
  Neuro-oncol, 4(1):26-38 (2002).  PubMed or Full Text pdf file
• Peña L.A., Fuks Z. and Kolesnick R.N.
  Radiation-induced Apoptosis of Endothelial Cells in the Murine Central Nervous System:Protection by Fibroblast Growth Factor and Sphingomyelinase Deficiency.
  Cancer Res, 60(2):321-327 (2000).  PubMed or Full Text pdf file
• 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(3):506-512 (1999).  PubMed or Full Text pdf file
• Mathias S., Peña L.A. and Kolesnick R.N.
  Signal transduction of stress via ceramide.
  Biochem. J., 335( Pt 3):465-480 (1998).  PubMed or Full Text pdf file
• Peña L.A., Fuks Z. and Kolesnick R.N.
  Stress-induced apoptosis and the sphingomyelin pathway.
  Biochem. Pharmacol., 53(5):615-621 (1997).  PubMed or Full Text pdf file
• 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(2):189-199 (1996).  PubMed or Full Text pdf file
• Peña L.A., Brecher C.W. and Marshak D.R.
  b-Amyloid regulates gene expression of glialtrophic substances S100 in C6 glioma and primary astrocyte cultures.
  Mol. Brain Res., 34(1):118-126 (1995). PubMed or Full Text pdf file
• Zhong Y. and Peña L.A.
  A novel synaptic transmission mediated by a PACAP-like neuropeptide in Drosophila.
  Neuron, 14(3):527-536(1995). PubMed or Full Text pdf file