Robert Moir, Ph.D.

Headshot photo

Assistant Professor in Neurology, Harvard Medical School

Assistant Professor in Neurology, MGH Neurology Research

Dr. Moir obtained his PhD from the University of Melbourne in the laboratory of Professor Colin Masters, one of the pioneers and founders of the modern era of Alzheimer's disease research. He joined the research unit of Professor Rudolph Tanzi at Harvard Medical School and Massachusetts General Hospital in 1994 as a Postdoctoral fellow. He is now an assistant Professor with joint appointments at HMS and MGH and runs his own research laboratory located at the MIND research facility in Charlestown MA.

Funded Research

Project Description Researchers Funding
The Amylin Protein of Diabetes Mellitus is an Antimicrobial Peptide

The goal of this project is to determine whether the amylin (IAPP) protein has a role in innate immunity (similar to Abeta) in order to significantly advance our understanding of the origins of diabetes pathology and its possible linkage to Alzheimer’s disease.

2010 to 2013
$900,000
Potential for Host Cytotoxicity from Microbially-derived Abeta Oligomers

Alzheimer’s disease (AD) is the most common form of dementia in the elderly afflicting over 20 million people worldwide. Two decades of findings from cell biology, genetic, neuropathological, biochemical and animal studies overwhelmingly point to the β-amyloid peptide (Aβ) as the key protein in the disease’s pathology (see review by Hardy and Selkoe, 20001). Aβ appears to be a soluble component of normal brain. However, in AD brain the peptide accumulates as β-amyloid, an insoluble semi-crystalline deposit that is the hallmark of the disease pathology.

2009
$250,000
Investigation of Certain Properties of Mitochondria Membranes Related to AD

While the mechanism of Aβ cytotoxicity remains contentious, evidence is accumulating that membrane permiabilization plays a key role in the pathological activity of the peptide. This study will focus on role of Aβ oligomerization in the Aβ-mediated disruption of lipid bilayers.

2008
$200,000
Identification of Agents that Inhibit the Generation and Neurotoxicity of Cross-linked B-amyloid Protein Species

We have coined the term CAPS to describe cross-linked-Beta-amyloid protein species. CAPS, particularly dimeric forms, are highly neurotoxic. CAPS are also abundant in vivo, with dimeric species alone comprising as much as 40 percent of the total Abeta pool in late state AD brain. In this study we plan to screen compound libraries for potential therapeutic agents that attenuate the levels and/or cytotoxic activity of CAPS.

2006 to 2007
$200,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

B.V. Hooli, PhD, G. Mohapatra, PhD, M. Mattheisen, MD, A.R. Parrado, PhD, J.T. Roehr, MS, Y. Shen, PhD, J.F. Gusella, PhD, R. Moir, PhD, A.J. Saunders, PhD, C. Lange, PhD, R.E. Tanzi, PhD and L. Bertram, MD, Role of common and rare APP DNA sequence variants in Alzheimer disease, Neurology 78 , 78/16, April 17, 2012, 1250-1257
Kim M, Suh J, Romano D, Truong MH, Mullin K, Hooli B, Norton D, Tesco G, Elliot K, Wagner SL, Moir RD, Becker KD, Tanzi RE., Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate alpha-secretase activity., Human Molecular Genetics, Vol 18, Oct 15, 2009
Dong Y, Zhang G, Zhang B, Moir RD, Xia W, Marcantonio ER, Culley DJ, Crosby G, Tanzi RE, Xie Z, The Common Inhalational Anesthetic Sevoflurane Induces Apoptosis and Increases β-Amyloid Protein Levels, Archives of Neurology, Vol. 66 No. 5, May 2009
Xie Z, Culley DJ, Dong Y, Zhang G, Zhang B, Moir RD, Frosch MP, Crosby G, Tanzi RE. , The common inhalation anesthetic isoflurane induces caspase activation and increases Aβ level in vivo., Annals of Neurology, Volume 64, Dec 2008
Zhang B, Dong Y, Zhang G, Moir RD, Xia W, Yue Y, Tian M, Culley DJ, Crosby G, Tanzi RE, Xie Z, The inhalation anesthetic desflurane induces caspase activation and increases amyloid-beta protein levels under hypoxic conditions., J Biol Chem., 2;283(18), May 2, 2008, 11866-75
Xie Z, Dong Y, Maeda U, Moir R, Xia W, Culley DJ, Crosby G, Tanzi RE., The Inhalation Anaesthetic Isoflurane Induces a Vicious Cycle of Apoptosis and Aβ Accumulation., J. Neurosci., 27, 2007, 1247-1254