Carmela R. Abraham
Professor of Biochemistry
Department of Biochemistry
Boston University School of Medicine
Silvio Conte Building, K620
72 E. Concord Street
Boston, MA. 02118
Phone: 617-638-4308
Fax: 617-638-5339
Email: cabraham@bu.edu
Education:
B.Sc. Tel Aviv University
Ph.D., Harvard University, Cambridge, MA
Research Interests:
Our laboratory studies the molecular mechanisms leading to normal brain aging and culminating in Alzheimer’s disease. The rhesus monkey is our model system for understanding the changes that occur during physiologic aging. We have identified several proteins that play crucial roles in brain dysfunction leading to cognitive decline. One such protein is Klotho, a cytoprotective, anti aging, life-span protein involved in insulin signaling. We found that Klotho expression is considerably decreased in the aged brains of monkeys, rats and mice. We are now searching for the Klotho receptors in the brain and also studying its promoter region in the hope of identifying compounds that would increase its expression. On the Alzheimer’s disease front we study the biology of the amyloid precursor protein, the parent protein of the amyloid beta peptide, a peptide that accumulates in the brains of Alzheimer’s disease patients and causes irreversible neurodegeneration. We are investigating a number of pharmacological interventions aimed at reducing the levels of this toxic peptide in the brain.
Representative Publications:
1. Hinman, JD, Duce, JA, Siman, R, Hollander, W and Abraham, C.R. (2004) Activation of calpain-1 in myelin and microglia in the white matter of the aged rhesus monkey. J. Neurochem. 89:430-441.
2. Hinman, JD, Peters, A, Rosene, DL, Hollander, W, Rasband, M and Abraham, CR. (2005) Age-related molecular reorganization at the node of Ranvier. J. Comp. Neurol. 495:351-362.
3. Oh, SY, Ellenstein, A, Chen, C-D, Hinman, JD, Berg, EA, Costello, CE, Yamin, R, Neve, RL and Abraham, CR (2005) The Amyloid Precursor Protein interacts with Notch receptors. J. Neurosci. Res. 82:32-42.
4. Duce, JA, Hollander, W, Jaffe, R. and Abraham, CR. (2006) Early complement activation targets myelin and oligodendrocytes in the aged rhesus monkey brain. Neurobiol Aging. 27:633-644.
5. Chen, C-D, Oh, SY, Hinman, JD and Abraham, CR. (2006) Visualization of APP dimerization and APP-Notch heterodimerization in living cells using bimolecular fluorescence complementation. J. Neurochem, 97:30-43.
6. Yamin, R, Bagchi, S, Hildebrant, R, Scaloni, A, Widom, RL, and Abraham, CR. (2007) Acyl Peptide Hydrolase, a serine proteinase isolated from conditioned medium of neuroblastoma cells, degrades the amyloid ß peptide. J. Neurochem. 100:458-467.
7. Jinman, JD and Abraham, CR (2007) What’s behind the decline? – The role of white matter in brain aging. Neurochem. Res. 32:2023-31.
8. Chen, C-D, Podvin, S, Gillespie, E, Leeman, S and Abraham, CR. (2007) Insulin Stimulates the Cleavage and Release of the Extracellular Domain of Klotho via ADAM10 and ADAM17, PNAS. 104:19796-19801.
9. Duce, JA, Podvin, S, Hollander, W, Kipling, D, Rosene, DL and Abraham, CR. (2008) Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey. Glia. 56:106-17.
10. Hinman, JD, Oh, S-Y, Chen, C-D, Hollander, W and Abraham, CR. (2008) Age-dependent accumulation of ubiquitinated CNP in myelin lipid rafts. Glia. 56:118-33.
