Office Contact Info.
Phone: (631) 344-3604
Fax: (631) 344-2358
Mail address: Bldg. 490
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Louis A. Peña
Scientist
Telephone: (631) 344-8041
Lab: (631) 344-8042
Fax: (631) 344-5311
e-mail:
lpena@bnl.gov
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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.
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