Carmela R. Abraham, PhD

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


Member
Boston University
Evans Center for Interdisciplinary Biomedical Research


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


Title


Yr Title Project-Sub Proj Pubs
2016 Discovery of probes that enhance expression of the neuroprotective protein Klotho 1R56AG051638-01A1 2
2011 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIATORS AND DYSMYELINATION 5P41RR010888-15-5143 259
2011 IDENTIFY THE KLOTHO RECEPTOR AND ITS SIGNALING PATHWAY 5P41RR010888-15-5161 259
2011 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIIATORS AND DYSMYELINATION 5P01AG000001-34-25 162
2010 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIATORS AND DYSMYELINATION 5P41RR010888-14-6848 259
2010 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIIATORS AND DYSMYELINATION 5P01AG000001-33-25 162
2009 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIATORS AND DYSMYELINATION 5P41RR010888-13-6206 259
2009 TECH R&D CORE SUPPORT FOR AIDS RESEARCH 5P41RR010888-13-6220 259
2009 BIOCHEMICAL STUDIES OF INFLAMMATORY MEDIIATORS AND DYSMYELINATION 5P01AG000001-32-25 162
2008 DETERMINATION OF BINDING PARTNERS FOR AMYLOID PRECURSOR PROTEIN 5P41RR010888-12-5179 259
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.

iCite Analysis       Copy PMIDs To Clipboard

  1. Chen CD, Rudy MA, Zeldich E, Abraham CR. A method to specifically activate the Klotho promoter by using zinc finger proteins constructed from modular building blocks and from naturally engineered Egr1 transcription factor backbone. FASEB J. 2020 Jun; 34(6):7234-7246.View Related Profiles. PMID: 32347987
     
  2. Wolf EJ, Logue MW, Zhao X, Daskalakis NP, Morrison FG, Escarfulleri S, Stone A, Schichman SA, McGlinchey RE, Milberg WP, Chen C, Abraham CR, Miller MW. PTSD and the klotho longevity gene: Evaluation of longitudinal effects on inflammation via DNA methylation. Psychoneuroendocrinology. 2020 07; 117:104656.View Related Profiles. PMID: 32438247
     
  3. Chen CD, Li Y, Chen AK, Rudy MA, Nasse JS, Zeldich E, Polanco TJ, Abraham CR. Identification of the cleavage sites leading to the shed forms of human and mouse anti-aging and cognition-enhancing protein Klotho. PLoS One. 2020; 15(1):e0226382.View Related Profiles. PMID: 31929539
     
  4. Delitsikou V, Jarad G, Rajaram RD, Ino F, Rutkowski JM, Chen CD, Santos CXC, Scherer PE, Abraham CR, Shah AM, Feraille E, Miner JH, de Seigneux S. Klotho regulation by albuminuria is dependent on ATF3 and endoplasmic reticulum stress. FASEB J. 2020 02; 34(2):2087-2104. PMID: 31907991
     
  5. Zeldich E, Chen CD, Boden E, Howat B, Nasse JS, Zeldich D, Lambert AG, Yuste A, Cherry JD, Mathias RM, Ma Q, Lau NC, McKee AC, Hatzipetros T, Abraham CR. Klotho Is Neuroprotective in the Superoxide Dismutase (SOD1G93A) Mouse Model of ALS. J Mol Neurosci. 2019 Oct; 69(2):264-285.View Related Profiles. PMID: 31250273
     
  6. McGrath ER, Himali JJ, Levy D, Conner SC, Pase MP, Abraham CR, Courchesne P, Satizabal CL, Vasan RS, Beiser AS, Seshadri S. Circulating fibroblast growth factor 23 levels and incident dementia: The Framingham heart study. PLoS One. 2019; 14(3):e0213321.View Related Profiles. PMID: 30830941; DOI: 10.1371/journal.pone.0213321;
     
  7. Chen CD, Zeldich E, Khodr C, Camara K, Tung TY, Lauder EC, Mullen P, Polanco TJ, Liu YY, Zeldich D, Xia W, Van Nostrand WE, Brown LE, Porco JA, Abraham CR. Small Molecule Amyloid-ß Protein Precursor Processing Modulators Lower Amyloid-ß Peptide Levels via cKit Signaling. J Alzheimers Dis. 2019; 67(3):1089-1106.View Related Profiles. PMID: 30776010
     
  8. Ikezu T, Chen C, DeLeo AM, Zeldich E, Fallin MD, Kanaan NM, Lunetta KL, Abraham CR, Logue MW, Farrer LA. Tau Phosphorylation is Impacted by Rare AKAP9 Mutations Associated with Alzheimer Disease in African Americans. J Neuroimmune Pharmacol. 2018 06; 13(2):254-264.View Related Profiles. PMID: 29516269
     
  9. Robinson AA, Abraham CR, Rosene DL. Candidate molecular pathways of white matter vulnerability in the brain of normal aging rhesus monkeys. Geroscience. 2018 02; 40(1):31-47.View Related Profiles. PMID: 29357021
     
  10. Chen CD, Zeldich E, Li Y, Yuste A, Abraham CR. Activation of the Anti-Aging and Cognition-Enhancing Gene Klotho by CRISPR-dCas9 Transcriptional Effector Complex. J Mol Neurosci. 2018 Feb; 64(2):175-184.View Related Profiles. PMID: 29352444
     
Showing 10 of 138 results. Show More

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

Bar chart showing 133 publications over 39 distinct years, with a maximum of 10 publications in 1993

YearPublications
19801
19811
19822
19832
19843
19852
19865
19871
19882
19898
19904
19917
19924
199310
19944
19953
19968
19975
19985
19993
20004
20012
20032
20042
20052
20062
20073
20083
20091
20102
20114
20124
20134
20145
20152
20161
20183
20194
20203


Recent (within 3 months)

Klotho VS Variant Preserves Memory by Preventing Tangles

Alzheimer’s Forum 8/14/2020

Older

Klotho Protein Protects Brains of ALS Mice, Study Suggests

ALS News Today 7/2/2019

Anti-Aging Protein Shown To Be Neuroprotective

World Health 6/29/2019
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72 E. Concord St Silvio Conte (K)
Boston MA 02118
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