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David Hastings Cribbs

Professor in Residence, Neurology
School of Medicine

Ph.D., West Virginia University, 1979, Biochemistry

Phone: (949) 824-3482
Fax: (949) 824-2071
Email: cribbs@uci.edu

University of California, Irvine
1207 Gillespie Neuroscience Research Facility
Mail Code: 4540
Irvine, CA 92697

picture of David Hastings Cribbs

Research
Interests
Alzheimer's disease; Immunotherapy; Cerebral vascular pathology; Neurodegeneration
   
Academic
Distinctions
2008 Van den Noort Award for Outstanding Research, Department of Neurology, University of California, Irvine
American Society for Engineering Education (ASEE) Faculty Fellowship (1989-1993)
NIH Postdoctoral Fellowship (1980-1983)
Visiting Assistant Professor, Department of Biology, The Johns Hopkins University, Baltimore, MD (1986)
   
Appointments Department of Biophysics, The Johns Hopkins University, Baltimore, MD (1980-1983)
   
Research
Abstract
The long-term goal of my research is to identify the critical age-related factors responsible for the initiation and the progression of Alzheimer’s disease (AD). My current research interests have evolved from an appreciation that amyloid-β (Aß) peptide is an invariant feature in AD, and that this amyloidogenic peptide has the capacity to gain biological activity as it assemblies into oligomeric and fibrillar forms. Fibrillar deposits of Aß in AD are highly co-localized with inflammatory factors, particularly components of the complement pathway. More recently, I have been actively pursuing the design and development of Aß-immunotherapy (Aß-vaccine) as an experimental approach to test the Amyloid Cascade Hypothesis of AD, and as a potential intervention for the treatment of AD. I am now focusing my attention on the mechanism(s) involved in antibody-mediated clearance of Aß, as well as identifying risk factors associated with immunotherapy in elderly AD patients. Much of my current research involves the use of transgenic mouse models that mimic critical features of AD. Finally, I have begun to investigate the pathogenic mechanisms involved in cerebral vascular degeneration in AD, which are prominent features in approximately 85% of the cases, because immunotherapy appears to increase the risk of cerebral vascular hemorrhages.
   
Publications Movsesyan N, Ghochikyan A, Mkrtichyan M, Petrushina I, Davtyan H, Olkhanud PB, Head E, Biragyn A, Cribbs DH, Agadjanyan MG. Prototype DNA epitope vaccine prevents behavioral impairment and AD-like pathology in 3xTg-AD mouse model without inducing cerebral hemorrhages. PLoS One May 7;3(5):e2124. PMID: 18461171 (2008)
   
  Nichol KE, Poon WW, Parachikova AI, Cribbs DH, Glabe CG, and Cotman CW. Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid. J Neuroinflam 5:13doi:10.1186/1742-2094-5-13 PMID: 18400101 (2008)
   
  Head E, Pop V, Vasilevko V, Hill M, Saing T, Sarsoza F, Nistor M, Christie LA, Milton S, Glabe C, Barrett E, Cribbs D. A two-year study with fibrillar beta-amyloid (Abeta) immunization in aged canines: effects on cognitive function and brain Abeta. J Neurosci. Apr 2;28(14):3555-66. PMID: 18385314 (2008)
   
  Mkrtichyan M, Ghochikyan A, Loukinov D, Davtyan H, Ichim TE, Cribbs DH, Lobanenkov VV, Agadjanyan MG. DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumor growth and prolongs the survival of mice. Gene Ther Jan; 15(1):61-64 PMID: 17972923 (2008)
   
  Vasilevko V, Xu F, Previti ML, Van Nostrand WE, and Cribbs DH. Experimental investigation of antibody-mediated clearance mechanisms of amyloid-ß in CNS of Tg-SwDI transgenic mice. J Neurosci Dec 5;27(49):13376-83. PMID: 18057195 (2007)
   
  Petrushina I, Ghochikyan A, Mktrichyan M, Mamikonyan G, Movsesyan N, Davtyan H, Patel A, Head E, Cribbs DH, Agadjanyan MG. The second generation therapeutic vaccine reduces insoluble but not soluble/oligomeric Aß species in APP/Tg mice. J Neurosci Nov 14;27(46):12721-12731. PMID: 18003852 (2007)
   
  Mamikonyan G, Necula M, Mkrtichyan M, Ghochikyan A, Petrushina I, Movsesyan N, Mina E, Kiyatkin A, Glabe C, Cribbs DH, Agadjanyan MG. Anti-Abeta 1-11 antibody binds to different beta-amyloid species, inhibits fibril formation, and disaggregates preformed fibrils, but not the most toxic oligomers. J Biol Chem 282:22376-22386 PMID: 17545160 (2007)
   
  Ghochikyan, A, Mkrtichyan, M, Loukinov, D, Mamikonyan, G, Pack, SD, Movsesyan, N, Ichim, TE, Cribbs, DH, Lobanenkov, VV, Agadjanyan, MG. Elicitation of T cell responses to histologically unrelated tumors by immunization with the novel cancer-testis antigen, brother of the regulator of imprinted sites. J Immunol 178:566-573 PMID: 17182597 (2007)
   
  Parachikova A, Agadjanyan MG, Cribbs DH, Blurton-Jones M, Perreau V, Rogers J, Beach TG, Cotman CW. Inflammatory changes parallel the early stages of Alzheimer disease. Neurobiol Aging 28:1821-33 PMID: 17052803 (2007)
   
  Ghochikyan, A, Petrushina, I, Lees A, Vasilevko, V, Movsesyan, N, Karapetyan, A, Agadjanyan, MG, Cribbs, DH. Abeta-immunotherapy for Alzheimer's disease using mannan-amyloid-Beta peptide immunoconjugates. DNA Cell Biol 10:571-580 PMID: 17132088 (2006)
   
  Oddo, S, Vasilevko, V, Caccamo, A, Kitazawa M, Cribbs DH, Laferla FM. Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J Biol Chem 28: 39413-39423 PMID: 17056594 (2006)
   
  Head E, Starr A, Kim RC, Parachikova A, Lopez GE, Dick M, Cribbs DH. Relapsing polychondritis with features of dementia with Lewy bodies. Acta Neuropathol (Berl) 112:217-25 PMID: 16832629 (2006)
   
  Vasilevko V, Cribbs DH. Novel approaches for immunotherapeutic intervention in Alzheimer's disease. Neurochem Int 49:113-26 PMID: 16765487 (2006)
   
  Head E, Barrett EG, Murphy MP, Das P, Nistor M, Sarsoza F, Glabe CC, Kayed R, Milton S, Vasilevko V, Milgram NW, Agadjanyan MG, Cribbs DH, Cotman CW. Immunization with fibrillar Abeta(1-42) in young and aged canines: Antibody generation and characteristics, and effects on CSF and brain Abeta. Vaccine 24:2824-34 PMID: 16460841 (2006)
   
  Ghochikyan A, Mkrtichyan M, Petrushina I, Movsesyan N, Karapetyan A, Cribbs DH, Agadjanyan MG. Prototype Alzheimer's disease epitope vaccine induced strong Th2-type anti-Abeta antibody response with Alum to Quil A adjuvant switch. Vaccine 24:2275-82 PMID: 16368167 (2006)
   
  Zhou, J., Fonseca, M.I., Hernandez, I., Kayed, R., Webster, S.D., Yazan, O., Cribbs, D.H., Glabe, C.G., and Tenner, A.J. Novel Aß peptide immunogens modulate plaque pathology and inflammation in a murine model of Alzheimer’s Disease. J Neuroinflam 2:28 PMID: 16332263 (2005)
   
  Taylor, A.M., Blurton-Jones, M., Rhee, S.W., Cribbs, D.H., Cotman, C.W., and Jeon, N.L. A Microfluidic Culture Platform for CNS Axonal Injury, Regeneration and Transport. Nature Methods 2:599-605 PMID: 16094385 (2005)
   
  Agadjanyan, M.G., Ghochikyan, A., Petrushina, I., Vasilevko, V., Movseayan, N., Mkrtichyan, M., Saing, T., and Cribbs, D.H. Prototype Alzheimer’s disease vaccine using the immunodominant B cell epitope from ß-amyloid and promiscuous T cell epitope Pan HLA DR-binding peptide. J Immunol 174:1580-1586 PMID: 15661919 (2005)
   
  Gevorkian, G., Petrushina, I., Manoutcharian, K.G., Ghochikyan, A., Acero, G., Vasilevko, V., Cribbs, D.H., and Agadjanyan, M.G. Mimotopes of conformational epitopes in fibrillar ß-amyloid. J Neuroimmunol 156:10-20 (2004)
   
  Cribbs D.H., Poon, W.W., Rissman, R.A., and Blurton-Jones, M. Caspase-mediated degeneration in Alzheimer's disease. Am J Path 165:353-355 PMID: 15277211 (2004)
   
  Oddo S., Billings, L., Kesslak, J.P., Cribbs, D.H., and LaFerla, F.M. Aß immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron 43:321-332 PMID: 15294141 (2004)
   
  Ghochikyan, A., Vasilevko, V., Petrushina, I., Movseayan, N., Babikyan, D., Tian, W., Sadzikava, N., Ross, T.M., Head, E., Cribbs, D.H., and Agadjanyan, M.G. Generation and characterization of the humoral immune responses to DNA immunization with a chimeric ß-amyloid-interleukin-4 minigene. Eur J Immunol 33:3232-3241 PMID: 14635031 (2003)
   
  Cribbs, D.H., Ghochikyan, A., Vasilevko, V., Tran, M., Petrushina, I., Sadzikava, N., Babikyan, D., Kieber-Emmons, T., Cotman, C.W., and Agadjanyan, M.G. Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with ß-amyloid. Int Immunol 15:505-514 PMID: 12663680 (2003)
   
Grants 2RO-1-AG020241-06 (PI Dr. David H. Cribbs) 10/01/06-06/30/11 Multiple Approaches to Aß Vaccination in Animal Models
   
RO-1 NS50895 (PI Dr. David H. Cribbs) 09/25/04 – 05/31/09 Combining AD Epitope Vaccine With Innate Immunity
   
PO1 AG000538 (Cotman, Carl W. Program Project Director) 2/01/08 - 1/31/13 NIH/NIA (Cribbs, David H. Project# 5 PI) Behavioral and neural plasticity in the aged (Project # 5) Oligomeric Aß and inflammation in neurovascular pathogenesis in AD
   
IIRG 0728314 (Ghochikyan, Anahit PI) 08/01/06 - 07/31/09 Investigator-Initiated Research Grant: Alzheimer’s Association (Cribbs, David H. Co-PI) Testing of AD DNA vaccine: protective vaccination versus therapeutic
   
Contract #: 43007717 (Co-PIs: Mark Fisher and David Cribbs) 3/01/08 - 9/30/09 Boehringer Ingelheim International GmbH Effects of Telmisartan (Micardis) and/or Dipyridamole on brain microvasculature
   
IIRG 91822 Alzheimer’s Association: Investigator Initiated Research Award 08/01/08 - 07/31/11 (Cribbs, David H. PI) Reducing the Risk of Cerebral Vascular Adverse Events in AD
   
UC MEXUS-CONACYT 07/01/2007-01/31/2008 0.6 calendar (Co-Principal Investigators Dr. David H. Cribbs and Dr. Goar Gevorkian) Selection of potentially therapeutic single chain antibodies directed against N-truncated forms of amyloid-beta peptide
   
Professional
Societies
Society for Neuroscience
American Association of Immunologists (AAI)
Federation of American Societies for Experimental Biology
Member of American Society for Neurochemistry (ASN)
International Society of NeuroImmunology (ISNI)
   
Other Experience Member of NIH Study Section, Brain Disorders and Clinical Neuroscience (BDCN-3)
National Institutes of Health 1998—2003

Ad hoc Reviewer for Alzheimer’s Association Research Grants
Alzheimer’s Association 1998—Pres

Ad hoc member of NIH Study Section, Cell Death and Injury in Neurodegeneration (CDIN
National Institutes of Health 2003—2004

Member of NIH Special Emphasis Panel (SEP) Study Section, RFA: Proteomics in Aging
National Institutes of Health 2004—2004

Editorial Board Member, Journal of Neuroinflammation
Journal of Neuroinflammation 2004—Pres

Member of NIH Study Section, Clinical Neuroimmunology and Brain Tumors (CNBT)
National Institutes of Health 2005—2009

Research Center Institute for Brain Aging and Dementia
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=5560
   
Last updated 09/16/2008