Benjamin Wolozin

Since 2008, Dr. Wolozin’s research has focused on the role of RNA binding proteins and stress granules in neurodegenerative diseases. RNA binding proteins contain domains that have only a few types of amino acids; these domains are termed "low complexity domains" and have a strong tendency to aggregate.[5] A highly unusual and important aspect of these proteins is that they use reversible aggregation as normal biological mechanism to sequester RNA transcripts. RNA binding proteins form a variety of cellular aggregates including stress granules, transport granules, P-bodies and nuclear speckles.[6] In 2010 Dr. Wolozin's group was one of the first groups to suggest that dysfunction of the stress granule pathway contributes to the pathophysiology of amyotrophic lateral sclerosis.[7] Since then, a growing body of evidence, increasingly highlights the important contributions of RNA-binding proteins (RBPs), stress granules and translational regulation in the pathophysiology of neurodegenerative disease. This work prompted the concept that “regulated protein aggregation”, which provides a theoretical framework for understanding the biology of neurodegenerative disease, including Alzheimer’s disease and Amyotrophic Lateral Sclerosis. The cell controls the location and disposition of RNA through the binding of RNA-binding proteins; these RNA binding proteins consolidate to form RNA granules through reversible aggregation of their low complexity domains. Recently, the biophysics of RNA granule formation has been shown to fall under the aegis of a general property, termed liquid liquid phase separation (LLPS).[8] LLPS occurs when RNA binding proteins associate to form structures analogous to liquid droplets, which separate from surrounding aqueous medium.

The Wolozin laboratory has extended this work to explain the pathophysiology of Alzheimer's disease [9][10] Work from the Wolozin laboratory demonstrates that the pathology occurring in neurons (neurofibrillary tangles) is associated with RNA binding proteins.[11][12] This appears to occur because tau (the main building block of neurofibrillary tangles) stimulates stress granule formation.[13] Importantly, the converse is also true. Stress granules appear able to stimulate tau pathology, leading to the hypothesis that Alzheimer's disease occurs in part because of a hyperactive stress granule response stimulated by chronic diseases and/or genetic changes, which results in abundant tau pathology and subsequent neurodegeneration.[14]

The stress granule/LLPS hypothesis is important because it identifies new directions for therapeutic intervention for tauopathies and other neurodegenerative diseases. Dr. Wolozin has developed methods to analyze the pathological RNA granules and stress granules that accumulate in brain diseases. He has also developed a series of compounds that potently and effectively inhibit TDP-43 aggregation in multiple neuronal models. In 2014, Dr. Wolozin combined forces with Glenn Larsen, Ph.D. to co-found the biotechnology company, Aquinnah Pharmaceuticals. Aquinnah Pharmaceuticals Inc. is dedicated to developing novel medicines to treat neurodegenerative diseases, and using a technology platform that focuses on the roles of RNA binding proteins, RNA metabolism and stress granules in neurodegenerative diseases.

Benjamin co-authored with Katya Ravid the scientists' pledge.[15] The pledge provides the equivalent for scientists of the Hippocratic Oath and is recited at graduation at some schools.