Carmela R. Abraham

Professor

Boston University School of Medicine
Silvio Conte Building, K304
72 E. Concord Street
Boston, MA. 02118

Phone: 617-638-4308
Lab Phone: 617-638-4315
Fax: 617-638-5339
Email: cabraham@bu.edu

Education

BSc, Biology, Tel Aviv University
PhD, Neuroscience, Harvard University, Cambridge, MA

People

Cidi Chen
Research Assistant Professor		 Ella Zeldich
Postdoctoral Fellow		 Tracey Tucker
Graduate Student
Christina Khodr
Postdoctoral Fellow

Lab Web Page

Research Interests

Our laboratory studies the molecular mechanisms leading to normal brain aging and the pathological processes that culminate in Alzheimer’s disease. We utilize the rhesus monkey as a model for understanding changes that occur during non-pathological aging. With microarray analysis we identified genes that play crucial roles in brain dysfunction leading to cognitive decline. An example is Klotho, a cytoprotective, anti-aging protein. We found that Klotho expression is considerably decreased in the aged brains of monkeys, rats, and mice. We are now working to comprehensively characterize the role of Klotho in normal aging and disease.  Our projects are to identify Klotho receptors in the brain and define the signaling pathways by which Klotho exerts its protective effects.  We are also studying Klotho’s transcriptional regulation and have identified compounds to therapeutically exploit these protective effects. Another line of investigation in our lab is to understand the biology of the amyloid precursor protein (APP), the parent protein of the amyloid beta peptide (Abeta), which accumulates in the brains of Alzheimer’s disease patients and causes irreversible neurodegeneration. Certain mutations in APP result in autosomal dominant, early onset familial Alzheimer’s disease due to the increased production of Abeta. Since APP homodimerization is believed to be involved in Abeta formation in the brain we searched and identified molecules capable of intervening in this process to reduce the levels of toxic Abeta peptide in the brain.

Research Themes

Neuroscience & Aging

Representative Publications

PubMed

  • Abraham, CR and Nagle, MW (2011) Acylaminoacyl-peptidase in Handbook of Proteolytic Enzymes, 3rd Edition.
  • Abraham, CR (2011) Amyloid beta peptide and the Amyloid cascade hypothesis. In The Handbook of Alzheimer’s Disease and Other Dementias, First Edition. Edited by Andrew E. Budson, Neil W. Kowall. Published by Blackwell Publishing Ltd.
  • King, GD, Rosene, DL and Abraham, CR (2011) Promoter methylation and age-related downregulation of klotho in rhesus monkey. AGE, Sept. 16. Epub.
  • So, P, Chen, C-D, and Abraham, CR (2011) Detection of Wild Type and Mutant Amyloid Precursor Protein Dimerization Using Beta-Galactosidase Enzyme Fragment Complementation. J. Alz Dis. 26:647-55.
  • Porat, ME, Lunetta, KL, Cupples, LA, Abraham, CR, Green, RC, Baldwin, CT and Farrer, LA (2010) Serum paraoxonase activity is associated with variants in the PON gene cluster and risk of Alzheimer disease. Neurobiol. Aging. Oct. 25.
  • Oh, S-Y, Chen, C-D, and Abraham, CR (2010) Cell-type Dependent Modulation of Notch Signaling by the Amyloid Precursor Protein. J. Neurochem. 113:262-74.
  • Zhao, Yamin R, O’Connor, Peter B, McKee, Ann C, Abraham, CR. (2009) Acyl Peptide Hydrolase Degrades Monomeric and Oligomeric Amyloid-Beta Peptide. Molecular Neurodegeneration. 4:33.
  • Cordy, JM, Zerbinatti, CV, Chen, C-D,Guillily, M, Suon, S, Ray, WJ, Seabrook, GR, Abraham, CR, and Wolozin, B. (2008) Oxysterol-binding protein-1 (OSBP-1) modulates processing and trafficking of the amyloid precursor protein. Molecular Neurodgeneration. 3:5.
  • 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.
  • 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.
  • 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.
  • Hinman, JD and Abraham, CR (2007) What’s behind the decline? – The role of white matter in brain aging. Neurochem. Res. 32:2023-31.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.