Massachusetts General Hospital

• Assistant Professor of Neurology, Harvard Medical School
• Department of Neurology, Massachusetts General Hospital

 

 

 

 

 

 

Research Description

Dr. Guénette’s research focuses on the molecular pathways that impact amyloid precursor protein (APP) function, as well as the generation and degradation of b-amyloid, a peptide central to the etiology of Alzheimer’s disease. It is now well established that the interaction of APP with the FE65 family of adaptor proteins in cultured cells modulates APP processing and b-amyloid peptide production.

Recent studies of the FE65/APP interaction have suggested that this protein complex may play a role in cell motility and transcriptional regulation. To address the biological significance of the FE65/APP interaction in vivo, we generated mice with targeted alleles of two FE65 protein family members and are actively characterizing the neurological phenotypes observed in the brains of these mice. Our studies of b-amyloid degradation focus on the importance of the insulin-degrading enzyme (IDE) for b-amyloid clearance in mice deficient for IDE.

Research interests	Amyloid precursor protein (APP) function, interaction of APP with FE65 adaptor proteins, transcriptional regulation
Research Techniques
Diseases studied	Alzheimer’s disease
Selected publications	Wolfe MS, Guénette SY.  APP at a glance. J Cell Sci. 2007 Sep 15;120(Pt 18):3157-61. Review. No abstract available. Huttunen HJ, Guénette SY, Peach C, Greco C, Xia W, Kim DY, Barren C, Tanzi RE, Kovacs DM. HtrA2 regulates beta-amyloid precursor protein (APP) metabolism through endoplasmic reticulum-associated degradation. J Biol Chem. 2007 Sep 21;282(38):28285-95. Epub 2007 Aug 6. Guénette SY. Mechanisms of Abeta clearance and catabolism. Neuromolecular Med. 2003;4(3):147-60. Review. Chang Y, Tesco G, Jeong WJ, Lindsley L, Eckman EA, Eckman CB, Tanzi RE, Guénette SY. Generation of the beta-amyloid peptide and the amyloid precursor protein C-terminal fragment gamma are potentiated by FE65L1. J Biol Chem. 2003 Dec 19;278(51):51100-7. Epub 2003 Oct 3. Guénette SY. Astrocytes: a cellular player in Abeta clearance and degradation. Trends Mol Med. 2003 Jul;9(7):279-80. No abstract available.
NCBI PubMed link	NCBI PubMed Publications
NIH biosketch	Suzanne Y. Guenette, PhD
E-mail address	Guenette@helix.mgh.harvard.edu
Lab mailing address	MassGeneral Institute for Neurodegenerative Disease 114 16th Street Charlestown, MA 02129
Lab telephone	617-726-3786
Lab, institute or center websites	www.mghmind.org