BBS Faculty Member - Dominic Walsh

Dominic Walsh

Department of Neurology

Brigham and Women's Hospital
Building for Transformative Medicine, Room 100020
60 Fenwood Road
Boston, MA 02115
Tel: 617-525-5059
Fax: 617-525-5252
Email: dwalsh3@partners.org



Amyloidogenic proteins such as the Alzheimer’s disease (AD) associated amyloid ß-protein (Aß) exist as soluble monomers that, under certain conditions, can form toxic assemblies. During the past 22 years my lab has been at the forefront of studies on the role of soluble Ab assemblies in AD and have published several landmark papers on this topic. Our primary goal is to study the process of protein aggregation and the neurotoxic events that result from it. In particular, we are interested in how these toxic assemblies affect synaptic form and function and in elucidating the earliest molecular changes they mediate. We apply a wide range of advanced biochemical, molecular, cell biological, electrophysiological and behavioural methods to decipher the basic mechanisms of neurodegeneration. The ultimate goal of our research is to generate sufficient information to allow the development of rationally designed drugs that will slow or halt disease.

We also have a growing interest in the aggregation and biology of the microtubule-associated protein, tau. We have recently shown that certain forms of tau are readily detected in the medium of iPS-derived human neurons, primary rat neurons and certain neuroblastoma cell lines. The bulk of tau in medium is unaggregated and in free solution, whereas a small proportion of tau is present in small microvesicles known and exosomes. We have an active research program centered on investigating the interactions between tau and Aβ.



Last Update: 12/8/2016



Publications

For a complete listing of publications click here.

 


 

Alexandra J. Mably, Wen Liu, Jessica M. Mc Donald, Jean-Cosme Dodart, Frédérique Bard, Cynthia A. Lemere, Brian O’Nuallain and Dominic M. Walsh. (2015) Anti-Aβ antibodies incapable of reducing cerebral Aβ oligomers fail to attenuate spatial reference memory deficits in J20 mice. Neurobiology of Disease. In press.

Daniel Kanmert, Adam Cantlon, Christina R. Muratore, Ming Jin, Gloria Lee, Tracy L. Young-Pearse, Dennis J. Selkoe and
Dominic M. Walsh. (2015) C-terminally truncated forms of tau, but not full length tau or its C-terminal fragments, are released from neurons independent of cell death. Journal of Neuroscience. In press.

Yona Levites, Brian O'Nuallain, Rama Devudu Puligedda, Tomas Ondrejcak, Sharad P. Adekar, Cindy Chen, Pedro E. Cruz, Awilda M. Rosario, Sallie Macy, Alexandra J. Mably,
Dominic M. Walsh, Ruben Vidal, Alan Solomon, Daniel Brown, Michael J. Rowan, Todd E. Golde, and Scott K. Dessain. (2015). A Human Monoclonal IgG that Binds Aβ Assemblies and Diverse Amyloids Exhibits Anti-Amyloid Activities In Vitro and In Vivo. Journal of Neuroscience. 35:6265-6276.

Adam Cantlon, Carlo Sala Frigerio, Darragh B. Freir, Barry Boland, Ming Jin,
Dominic M. Walsh. (2015). The familial British dementia mutation promotes formation of neurotoxic cystine cross-linked amyloid Bri (ABri) oligomers. Journal of Biological Chemistry. jbc.M115.652263. [Epub ahead of print].

Jessica M. Mc Donald, Tiernan T. O’Malley, Wen Liu, Alexandra J. Mably, Gunnar Brinkmalm, Erik Portelius, William W. Wittbold, Matthew P. Frosch and
Dominic M. Walsh. (2015). The aqueous phase of Alzheimer’s disease brain contains assemblies built from ~4 and ~7 kDa Aβ species. Alzheimer’s Disease and Dementia. jalz.2015.01.005. [Epub ahead of print].



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