Robert D. Moir, PhD

  • Lab Phone: 617 726 3746

Research Investigator Profile

Robert D. Moir, PhD

 

Robert D. Moir, PhD

  • Assistant Professor in Neurology,
    Harvard Medical School
  • Assistant Professor in Neurology,
    MGH Neurology Research

 

Research Description

My research focuses on the biochemical and cellular mechanisms involved in neurodegeneration in Alzheimer's disease (AD) and aging. More specifically, receptor/ligand interactions and physiochemical properties that promote pathological protein behavior. Particular emphasis has been placed on the beta-amyloid peptide (A beta), amyloid precursor protein (APP), apolipoprotein E, low density lipoprotein receptor protein (LRP), alpha-2-macroblobulin and the presenilins (PS1 and PS2).

My body of work includes studies that identify LRP as the cell surface receptor for APP and the receptor that mediates the first step in the pathway that ultimately leads to amyloid deposition in AD brain, and characterization of the role and importance of metals in the pathological physiochemistry of A beta (the principal component of amyloid in AD) and of the clinical potential of chelators in AD treatment. My most recent studies have focused on identifying the normal function of A beta. The findings from these studies suggest A beta is a member of the family of essential innate immune effector biomolecules known as antimicrobial peptides.

Research interests Beta-amyloid peptide, antimicrobial peptide, Alzheimer's disease, innate immunity, neurodegeneration, amyloid protein precursor, apolipoprotein E
Research techniques Peptide analysis, immunodetection, ELISA, Western bloting, immunoprecipitation, binding assays, antimicrobial activity, solubility, aggregation, cytotoxicity assays, redox activity
Diseases studied Neurodegenerative diseases; Alzheimer's disease, AIDS dementia
Selected publications
  1. Kounnas MZ, Moir RD, Rebeck CW, Bush AI, Argraves WS, Tanzi RE, Hyman BT and Strickland DK. LDL receptor-related protein, a mulitfunctional apolipoprotein E receptor, binds secreted beta-amyloid precursor protein and mediates its degradation. Cell 1995; 82: 331 40.
  2. Moir RD, Lynch T, Bush AI, Multhaup G, Whyte S, Tanzi RE, Small DH, Beyreuther, K and Masters, CL. Relative increase in Alzheimer's disease of soluble forms of cerebral A beta amyloid protein precursor containing the Kunitz Protease Inhibitory domain. J. Biol. Chem. 1998; 273: 5013-5019.
  3. Moir RD, Bush AI, Romano DM, Atwood CS, Huang X., Smith J and Tanzi RE. Differential effects of apolipoprotein E isoforms on metal-induced aggregation of A beta under physiological conditions. Biochemistry 1999; 38: 4595-4603.
  4. Goldstein LE, Muffat JA, Cherny RA, Moir RD, Ericsson MH, Huang X, Mavros C, Coccia JA, Faget KY, Fitch KA, Masters CL, Tanzi RE, Chylack LT, Bush AI. Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease. Lancet 2003; 361: 1258-1265.
  5. Soscia SJ, Kirby JE, Washicosky KJ, Tucker SM, Ingelsson M, Hyman B, Burton MA, Goldstein LE, Duong S, Tanzi RE, Moir RD. The Alzheimer’s Disease-Associated Amyloid-beta Protein Is an Antimicrobial Peptide. PLoS ONE 2010; 5 (3): 1-10.
NCBI PubMed link NCBI PubMed Publications
NIH biosketch Robert D. Moir, PhD
E-mail address moir@helix.mgh.harvard.edu
Lab mailing address Genetics and Aging Research Unit
Massachusetts General Hospital
MassGeneral Institute for Neurodegenerative Disease
Building 114, 16th Street
Charlestown, MA  02129-4404
USA
Lab website

Moir Lab, Genetics and Aging Research Unit, MIND

MIND Faculty Profile