Background & Research Interests:

Dan earned a B.S. in Behavioral Neuroscience from Northeastern University in 2012, graduating summa cum laude from the College of Science Honor’s Program. Prior to beginning his graduate work in the Biomolecular Pharmacology Ph.D. program at Boston University, Dan worked as a research assistant at Biogen Idec where he studied mechanisms of axonal regeneration and remyelination in animal and cell culture models of Multiple Sclerosis and Amyotrophic Lateral Sclerosis. Dan’s long term research interests focus on the discovery and development of disease modifying therapies for the treatment of neurodegenerative disorders.

Thesis Research at BU:

RNA binding proteins have diverse regulatory roles in the transcription, splicing, transport, translation, and stability of mRNA transcripts. Notably, RNA binding proteins are particularly crucial in neuronal cells which require extensive transport of mRNAs to synapses in order to facilitate the local regulation of activity-dependent protein synthesis required for the synaptic plasticity that underlies learning and memory. RNA binding proteins also mediate the reversible aggregation of stress granules, which are cytoplasmic inclusions of mRNA and protein that form transiently in response to stress-induced inhibition of global protein synthesis. Our lab has discovered that stress granules colocalize with the intraneuronal pathological tau inclusions that are characteristic of Alzheimer’s disease (AD), suggesting that tau aggregation in AD and related tauopathies might be regulated by the same processes controlling the reversible aggregation of stress granules. In AD tissue, tau directly associates with the RNA binding proteins that nucleate stress granule assembly, while stimulation of stress granule formation promotes tau pathology and neurotoxicity in primary cultured neurons. These findings identify a novel aspect of disease pathophysiology and suggest a mechanism whereby the excessive recruitment of RNA binding proteins to stress granules in disease would inhibit the normal function of RNA binding proteins in mediating mRNA splicing, transport, and translation at the synapse leading to neurodegeneration. Current aims of the project include: 1) identification of the proteins associated with pathological tau stress granules; 2) to determine how mRNA splicing and transport are modulated by chronic stress granule formation in the presence and absence of tau; 3) to determine whether inhibition of stress granule formation ameliorates disease progression in P301L tau transgenic AD mice; and 4) to elucidate the cellular stress pathways responsible for inducing pathological tau stress granules and the role of tau phosphorylation in regulating this process.