Research area: Neuroimmunology, Neurodegenration.

Current Research Topics:  The role  of glia cells during central nervous system inflammation using models of stroke and Alzheimer's disease.

Methods & Techniques: Immunology, Cell biology, Molecular biology, Histology.

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     Although neurodegenerative diseases are not considered immune mediated, the nature of the immune response is crucial in the application of immunotherapeutic approaches.Resting glia cells are highly sensitive to changes in the tissue microenvironment. Activation is associated with increased production of potentially cytotoxic molecules, including reactive oxygen species (ROS), proteases, and pro-inflammatory cytokines, together with induction of phagocytosis. Their role however, is complex, and different subsets of glia cells can be neuroprotective or neurotoxic. The presence of recruited leukocytes at the site of inflammation is critically dependent upon the coordinated expression of adhesion molecules, ligands and receptors on inflammatory cells and the activated capillary endothelium, respectively. Modulation of neuroinflammation may have applicability both as a preventative therapy and as a treatment in stress and neurodegenerative diseases.

        The research in the lab is focused on understanding glia-neuron interaction to further understand their role in neurological diseases both in culture and in vivo using models of stroke, Alzheimer's disease, and multiple sclerosis.

Solomon B., Koppel R., Frenkel D. and Hanan-Aharon E. Disaggregation of Alzheimer b-Amyloid by site-directed mAb, Proc. Natl. Acad. Sci. USA 94:4109-4112 1997.

Frenkel D., Balass M. and Solomon B. N-Terminal EFRH sequence of Alzheimer’s b-amyloid peptide represents the epitope of its anti-aggregation antibodies. J. Neuroimmunology 88:85-90 1998.

Frenkel D., Balass M., Katchalski-Katzir E. and Solomon B. High affinity binding of monoclonal antibodies to the sequential epitope EFRH of b-amyloid peptide is esstential for modulation of fibrillar aggregation. J. Neuroimmunology 95:136-142 1999.

Berdichevsky Y., Lamed R., Frenkel D., Gophna U., Bayer E.E., Yaron S., Shoham Y.  and Benhar I. Matrix-assisted refolding of single-chain Fv-cellulose binding domain fusion proteins. Protein Expression and Purification 17:249-259 1999.

Frenkel D., Solomon B. and Benhar I. Modulation of Alzheimer’s b-Amyloid Neurotoxicity by Site-Directed Single-Chain Antibody,  J. Neuroimmunology 106(1-2):23-31 2000.

Solomon B and Frenkel D. Vaccination for the prevention and treatment of Alzheimer's disease. Drugs of Today 36(9):655-663 2000.

Frenkel D., Katz O. and Solomon B. Immunization against Alzheimer’s b-Amyloid plaques via EFRH-phage administration. Proc. Natl. Acad. Sci. USA 97(21):11455-11459 2000.

Frenkel D., Kariv N. and Solomon B. Generation of auto-antibodies towards alzheimer’s disease vaccination, Vaccine,  19(17-19):2615-9 2001.

Frenkel D and Solomon B, Towards Alzheimer’s disease vaccination,  Biologicals , 29(3-4):243-7 2001.

Frenkel D, Solomon B., Filamentous phage as vector-mediated antibody delivery to  the brain, Proc Natl Acad Sci USA;99(8):5675-9 2002.

Solomon B and Frenkel D., Generation and brain delivery of anti-aggregating antibodies against beta-amyloid plaques using phage display technology.  J Neural Transm Suppl ;(62):321-5 2002.

Frenkel D, Dewachter I, Van Leuven F, Solomon B., Reduction of beta-amyloid plaques in brain of transgenic mouse model of Alzheimer's disease by EFRH-phage immunization.  Vaccine ,21(11-12):1060-5 2003.

Frenkel D, Huang Z, Maron R, Koldzic DN, Hancock WW, Moskowitz MA, Weiner HL. Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+ T cells. J Immunol., 171(12):6549-55 2003.

Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder   EY, Khoury SJ.(2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U SA 28;101(52):18117-22.

Frenkel D, Huang Z, Maron R, Koldzic DN, Hancock WW, Moskowitz MA, Weiner HL. (2005). Neuroprotection by IL-10-producing MOG CD4+ T cells following ischemic stroke.  J Neurol Sci 15;233(1-2):125-32.

Frenkel D, Maron R, Burt DS, Weiner HL (2005), Nasal vaccination with a proteosome-based adjuvant and glatiramer acetate clears  b-amyloid in a mouse model of Alzheimer's disease. JCI, 115(9):2423-2433.

Zhang X, Reddy J, Ochi H, Frenkel D, Kuchroo VK, Weiner HL (2006). Recovery from experimental allergic encephalomyelitis is TGF-{beta} dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells. Int Immunol. 18(4):495-503.

Weiner HL, Frenkel D (2006). Immunology and immunotherapy of Alzheimer's  disease. Nat Rev Immunol. 6(5):404-16.

Ochi H, Abraham M, Ishikawa H, Frenkel D, Yang K, Basso AS, Wu H, Chen ML,Gandhi R, Miller A, Maron R, Weiner HL. (2006) Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4(+)CD25(-)LAP(+) T cells.Nat Med. 12(6):627-35.