Benjamin L. Wolozin, MD, PhD

Biography

Dr. Wolozin has extensive research experience in the field of neurodegenerative disease. His research investigates the pathophysiology of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis.

His research examines molecular and cellular aspects of disease, and he has extensive experience in molecular neuropathology. His work utilizes studies of human tissues as well as a variety of transgenic models including mice, primary neurons and cell lines. Dr. Wolozin has extensive experience in cell culture, including iPSCs, primary cultures of hippocampal and cortical neurons and cell lines. The lab has increasingly worked with iPSCs particularly focusing on development and application of the human 3D iPS-Neuron/Astrocyte assembloids that rapidly develop Alzheimer pathology.

Dr. Wolozin’s research on the role of stress granules in neurodegenerative diseases is a major focus of his laboratory. A growing body of evidence, including work from the Wolozin laboratory, increasingly highlights the important contributions of RNA binding proteins (RBPs) and translational regulation in the pathophysiology of neurodegenerative disease. This field of research has occupied a correspondingly increasing footprint on the Wolozin laboratory research portfolio. This work has prompted concepts that are changing our understanding of protein association and disease processes; terms such as “regulated protein aggregation”, “membraneless organelles” or “liquid-liquid phase separation”, provide a theoretical framework for understanding the biology of neurodegenerative disease, as well as new directions for therapeutic intervention for tauopathies and other neurodegenerative diseases. RBPs are regulated through formation of membraneless organelles, which brings aggregation prone proteins together at high concentrations. The process is designed to respond to transient stresses in a transient, dynamic manner. The membraneless organelles that for during transient stress are termed “stress granules”. Chronic metabolic or environmental stress (and aging) lead to persistence of these stress granules, allowing time for protein aggregation to occur, which then drives disease. These persistent stress granules (as well as other persistent membraneless organelles) ultimately serve as the nidus for formation of the pathology present in diseases such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis.

The Wolozin Lab has developed methods to analyze the pathological RNA granules and stress granules that accumulate in brain diseases. Through his research we have demonstrated an important role for RNA binding proteins in the pathophysiology of Alzheimer’s disease, demonstrating that reducing the RNA binding proteins, such as TIA1 or HNRNPA2B1, block the accumulation of a type of pathology that accumulates in neuron in the Alzheimer’s disease brain. Recently, Dr. Wolozin’s laboratory has focused on the role played by post-transcriptional modifications of RNA in the translational stress response and the pathophysiology of neurodegenerative diseases. The studies led to identification of major increases in RNA methylation in AD & ADRD, and are leading to investigation of novel disease-linked functions of RBPs that regulate methylated mRNA, termed m6A, as well as the many ncRNAs that are preferentially methylated in disease. Dr. Wolozin’s laboratory has also been studying noncoding RNAs in collaboration with Dr. Xiaoling Zhang. We recently identified disease-linked changes in circRNA levels, and are determining the functional attributes of these circRNA.