Our long term interest is to understand the molecular mechanisms that underlie plasticity in the nervous system and to exploit these to predictably modify the intact and damaged nervous system. To this end we have developed several lines of investigation:

      1) Development of herpes virus vectors to direct expression of therapeutic genes long term to different cellular compartments within the intact CNS. This project involves vector development with the goal of eliminating somatic cell extinction of transgene expression;

       2) Eludicating the role of NGF in the adult hippocampus. A binary germline-somatic transgene system based on loxP/cre recombinase is being exploited to produce postnatal genetic mosiacism for NGF gain of function. Molecular, anatomic and behavioral assays are utilized to assess changes in the function of the NGF-responsive septohippocampal pathway;

      3) Development of somatic mosiac mice to examine the syngergy between environmental neurotoxicants and specific neuronal vulnerability genes as a model for Parkinson's disease. Somatic gain of gene function is produced by targeted cre recombinase delivery to generate the vulnerability state and followed by subsequent neurotoxicant exposure. Multiple levels of analyses are undertaken.

      4) Modulation of sympathetic neural input by neurotrophic factor dysregulation. We have made transgenic animals to manipulate nerve growth factor (NGF) levels to dissect out its different functions in the developing and mature nervous system. Tissue specific constitutive expression of NGF results in sympathetic hyperinnervation of the expressing target organ and developmental perturbation of the neural crest contributions to that target organ.

Recent Publications

Miller RM, Federoff HJ. 2006. Microarrays in Parkinson’s disease: a systematic approach. NeuroRx. Jul;3(3):319-326.

Federoff HJ, Mhyre TR. 2006. Systems biology: a primer. NeuroRx. Jul;3(3):293-294.

Tyler CM, Federoff HJ. 2006. CNS gene therapy and a nexus of complexity: systems and biology at a crossroads. Cell Transplant. 15(3):267-273. Review.

Rempe D, Vangeison G, Hamilton J, Li Y, Jepson M, Federoff HJ. 2006. Synapsin I Cre transgene expression in male mice produces germline recombination in progeny. Genesis. Jan;44(1):44-49

Bowers WJ, Mastrangelo MA, Howard DF, Southerland HA, Maguire-Zeiss KA, Federoff HJ. 2006. Neuronal precursor-restricted transduction via in utero CNS gene delivery of a novel bipartite HSV amplicon/transposase hybrid vector. Mol Ther. Mar;13(3):580-588.

Weimer JM, Custer AW, Benedict JW, Alexander NA, Kingsley E, Federoff HJ, Cooper JD, Pearce DA. 2006. Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons. Neurobiol Dis. May;22(2):284-293

Arvanian VL, Bowers WJ, Anderson A, Horner PJ, Federoff HJ, Mendell LM. 2006. Combined delivery of neurotrophin-3 and NMDA receptors 2D subunit strengthens synaptic transmission in contused and staggered double hemisected spinal cord of neonatal rat. Exp Neurol. Feb;197(2):347-52.

Miller RM, Kiser GL, Kaysser-Kranich TM, Lockner RJ, Palaniappan C, Federoff HJ. 2006. Robust dysregulation of gene expression in substantia nigra and striatum in Parkinson's disease. Neurobiol Dis. Feb;21(2):305-313.

Maguire-Zeiss KA, Federoff HJ. 2005. Novel gene therapeutic strategies for neurodegenerative diseases. Ernst Schering Res Found Workshop. (53):147-171. Review.

Federoff HJ, Bowers WJ. 2005. Immune shaping and the development of Alzheimer’s disease vaccines. Sci Aging Knowledge Environ. Nov 16;2005(46):pe35. Review.

Miller RM, Federoff HJ. 2005. Altered gene expression profiles reveal similarities and differences between Parkinson disease and model systems. Neuroscientist. Dec;11(6):539-549. Review.

Reinblatt M, Pin RH, Bowers WJ, Federoff HJ, Fong Y. 2005. Herpes simplex virus amplicon delivery of a hypoxia-inducible soluble vascular endothelial growth factor receptor (sFlk-1) inhibits angiogenesis and tumor growth in pancreatic adenocarcinoma. Ann Surg Oncol. Dec;12(12):1025-1036.

Janelsins MC, Mastrangelo MA, Oddo S, LaFerla FM, Federoff HJ, Bowers WJ. 2005. Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice. J Neuroinflammation. Oct 18;2:23.

de Pina-Benabou MH, Szostak V, Kyrozis A, Rempe D, Uziel D, Urban-Maldonado M, Benabou S, Spray DC, Federoff HJ, Stanton PK, Rozental R. 2005. Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia. Stroke. Oct;36(10):2232-2237.

Tyler CM, Wuertzer CA, Bowers WJ, Federoff HJ. 2006. HSV Amplicons: Neuro Applications. Curr Gene Ther. Jun;6(3):337-350.

Kyrkanides S, Miller JH, Brouxhon SM, Olschowka JA, Federoff HJ. 2005. beta-hexosaminidase lentiviral vectors: transfer into the CNS via systemic administration. Brain Res Mol Brain Res. Feb 18;133(2):286-298.

Miller RM, Chen LL, Kiser GL, Giesler TL, Kaysser-Kranich TM, Palaniappan C, Federoff HJ. 2005. Temporal evolution of mouse striatal gene expression following MPTP injury. Neurobiol Aging. May;26(5):765-775.

Gorantla S, Santos K, Meyer V, Dewhurst S, Bowers WJ, Federoff HJ, Gendelman HE, Poluektova L. 2005. Human dendritic cells transduced with herpes simplex virus amplicons encoding human immunodeficiency virus type 1 (HIV-1) gp120 elicit adaptive immune responses from human cells engrafted into NOD/SCID mice and confer partial protection against HIV-1 challenge. J Virol. Feb;79(4):2124-2132

Bowers WJ, Mastrangelo MA, Stanley HA, Casey AE, Milo LJ Jr, and Federoff HJ. 2005. HSV amplicon-mediated Abeta vaccination in Tg2576 mice: differential antigen-specific immune responses. Neurobiol Aging. Apr;26(4):393-407.