Carmela R. Abraham, PhD
Professor
Boston University School of Medicine
Dept of Biochemistry

PhD, Harvard University



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.

Professor
Boston University School of Medicine
Pharmacology & Experimental Therapeutics


Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Division of Graduate Medical Sciences



2011 Society for Neuroscience: Abstract Chosen for Hot Topics (<1% were chosen)
2011 Boston Medical Center: Nominated for Collaborator of the Year Award
2011 Boston University: The Ignition Award
1999 Alzheimer’s Association: The T.L.L. Temple Award
1994 Alzheimer's Association: The Zenith Award
1990 The Neuroscience Education and Research Foundation: Award for an Outstanding Promise as a Young Alzheimer Investigator
1990 Weil Honorable Mention for the Best Paper in Experimental Neuropathology
1988 Center for Neurologic Diseases: The Second Rappaport Award for the Study of Alzheimer's Disease
1987-1989 The Albert J. Ryan Fellowship
1987 Center for Neurologic Diseases: The First Rappaport Award for the Study of Alzheimer's Disease
1987-1989 The Freudenberger Scholarship


Discovery of probes that enhance expression of the neuroprotective protein Klotho
09/15/2016 - 08/31/2018 (PI)
NIH/National Institute on Aging
1R56AG051638-01A1

Development of Novel APP Dimerization Inhibitors that Lower A-beta Levels
09/01/2015 - 04/01/2018 (PI)
Cure Alzheimer's Fund


Development of Klotho Enhancers as Novel Therapeutics for AD
06/01/2016 - 02/28/2018 (PI)
Alzheimer's Drug Discovery Foundation


Klotho-enhancing compounds as potential new treatments for demyelinating diseases
11/01/2014 - 01/31/2018 (PI)
Massachusetts Neuroscience Consortium


Development of Klotho Enhancers as Novel Therapeutics for AD
05/15/2015 - 03/15/2017 (PI)
Alzheimer's Drug Discovery Foundation


Development of Klotho Enhancers as Novel Therapeutics for AD
05/01/2014 - 05/01/2015 (PI)
Alzheimer's Drug Discovery Foundation


Development of Klotho Enhancers as Novel Therapeutics for AD
06/01/2013 - 05/31/2014 (PI)
Alzheimer's Drug Discovery Foundation


Modulators of APP Dimerization as Novel Therapeutics for Alzheimer's Disease
03/01/2011 - 02/28/2014 (PI)
Alzheimer's Association


Development of Klotho Enhancers as Novel Therapeutics for AD
07/01/2012 - 05/31/2013 (PI)
Alzheimer's Drug Discovery Foundation


Proposal to Study Function of Klotho in the Normal and Aging Brain
05/01/2006 - 04/30/2010 (PI)
Anonymous

Showing 10 of 16 results. Show All Results



Yr Title Project-Sub Proj Pubs
2016 Discovery of probes that enhance expression of the neuroprotective protein Klotho 1R56AG051638-01A1
2011 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIATORS AND DYSMYELINATION 5P41RR010888-15-5143 236
2011 IDENTIFY THE KLOTHO RECEPTOR AND ITS SIGNALING PATHWAY 5P41RR010888-15-5161 236
2011 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIIATORS AND DYSMYELINATION 5P01AG000001-34-25 123
2010 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIATORS AND DYSMYELINATION 5P41RR010888-14-6848 236
2010 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIIATORS AND DYSMYELINATION 5P01AG000001-33-25 123
2009 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIATORS AND DYSMYELINATION 5P41RR010888-13-6206 236
2009 TECH R&D CORE SUPPORT FOR AIDS RESEARCH 5P41RR010888-13-6220 236
2009 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIIATORS AND DYSMYELINATION 5P01AG000001-32-25 123
2008 DETERMINATION OF BINDING PARTNERS FOR AMYLOID PRECURSOR PROTEIN 5P41RR010888-12-5179 236
Showing 10 of 33 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Abraham CR, Mullen PC, Tucker-Zhou T, Chen CD, Zeldich E. Klotho Is a Neuroprotective and Cognition-Enhancing Protein. Vitam Horm. 2016; 101:215-38.View Related Profiles. PMID: 27125744; DOI: 10.1016/bs.vh.2016.02.004;.
  2. Zeldich E, Chen CD, Avila R, Medicetty S, Abraham CR. The Anti-Aging Protein Klotho Enhances Remyelination Following Cuprizone-Induced Demyelination. J Mol Neurosci. 2015 Oct; 57(2):185-96.View Related Profiles. PMID: 26067431; DOI: 10.1007/s12031-015-0598-2;.
  3. Dubal DB, Zhu L, Sanchez PE, Worden K, Broestl L, Johnson E, Ho K, Yu GQ, Kim D, Betourne A, Kuro-O M, Masliah E, Abraham CR, Mucke L. Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice. J Neurosci. 2015 Feb 11; 35(6):2358-71. PMID: 25673831; PMCID: PMC4323521; DOI: 10.1523/JNEUROSCI.5791-12.2015;.
  4. Chen CD, Tung TY, Liang J, Zeldich E, Tucker Zhou TB, Turk BE, Abraham CR. Identification of cleavage sites leading to the shed form of the anti-aging protein klotho. Biochemistry. 2014 Sep 2; 53(34):5579-87.View Related Profiles. PMID: 25110992; PMCID: PMC4151695; DOI: 10.1021/bi500409n;.
  5. Jun G, Asai H, Zeldich E, Drapeau E, Chen C, Chung J, Park JH, Kim S, Haroutunian V, Foroud T, Kuwano R, Haines JL, Pericak-Vance MA, Schellenberg GD, Lunetta KL, Kim JW, Buxbaum JD, Mayeux R, Ikezu T, Abraham CR, Farrer LA. PLXNA4 is associated with Alzheimer disease and modulates tau phosphorylation. Ann Neurol. 2014 Sep; 76(3):379-92.View Related Profiles. PMID: 25043464; DOI: 10.1002/ana.24219;.
  6. Zeldich E, Chen CD, Colvin TA, Bove-Fenderson EA, Liang J, Tucker Zhou TB, Harris DA, Abraham CR. The neuroprotective effect of Klotho is mediated via regulation of members of the redox system. J Biol Chem. 2014 Aug 29; 289(35):24700-15.View Related Profiles. PMID: 25037225; PMCID: PMC4148892; DOI: 10.1074/jbc.M114.567321;.
  7. Chen CD, Li H, Liang J, Hixson K, Zeldich E, Abraham CR. The anti-aging and tumor suppressor protein Klotho enhances differentiation of a human oligodendrocytic hybrid cell line. J Mol Neurosci. 2015 Jan; 55(1):76-90.View Related Profiles. PMID: 24907942; DOI: 10.1007/s12031-014-0336-1;.
  8. Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L. Life extension factor klotho enhances cognition. Cell Rep. 2014 May 22; 7(4):1065-76. PMID: 24813892; PMCID: PMC4176932; DOI: 10.1016/j.celrep.2014.03.076;.
  9. Tucker Zhou TB, King GD, Chen C, Abraham CR. Biochemical and functional characterization of the klotho-VS polymorphism implicated in aging and disease risk. J Biol Chem. 2013 Dec 20; 288(51):36302-11. PMID: 24217253; PMCID: PMC3868745; DOI: 10.1074/jbc.M113.490052;.
  10. Mehi SJ, Maltare A, Abraham CR, King GD. MicroRNA-339 and microRNA-556 regulate Klotho expression in vitro. Age (Dordr). 2014 Feb; 36(1):141-9. PMID: 23818104; PMCID: PMC3889880; DOI: 10.1007/s11357-013-9555-6;.
Showing 10 of 123 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 118 publications over 36 distinct years, with a maximum of 10 publications in 1993

YearPublications
19801
19811
19822
19831
19841
19851
19864
19871
19882
19898
19904
19917
19924
199310
19944
19953
19968
19975
19985
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20042
20052
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20073
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20102
20114
20124
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20161
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72 E. Concord St Silvio Conte (K)
Boston MA 02118
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