Biography

Daryl Bosco received her Ph.D. (bio-organic chemistry) in 2003 from Brandeis University, where she used NMR spectroscopy to study enzyme dynamics.  From 2003-2005, Dr. Bosco was a post-doctoral fellow in the lab of Jeffery W. Kelly at the Scripps Research Institute, where she studied the effect of oxidative cholesterol metabolites on the mis-folding of alpha-synuclein, a Parkinson's disease-associated protein. Prior to joining the faculty at UMMS in 2008, Dr. Bosco was an Instructor of Neurology at Harvard Medical School and worked on various aspects of ALS in the Cecile B. Day lab directed by Dr. Robert H. Brown, Jr. at the Massachusetts General Hospital.

Research

Elucidating the factors involved in sporadic ALS

One focus of my lab is to elucidate the molecular mechanism(s) underlying sporadic forms of neurodegenerative diseases, with a focus on amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease.  Approximately 10% of ALS cases are inherited or familial in nature (FALS), whereas the vast majority (~90%) of cases have an unknown etiology and are thus classified as sporadic ALS (SALS).  The factors involved in SALS have yet to be identified; the challenge being that sporadic forms of neurodegenerative diseases are multifactorial, involving a complex interplay between genetics and environment.  Our goal is to develop relevant models to identify genetic and environmental factors involved in SALS pathogenesis.

Investigating the misfolding of SOD1 wild-type in sporadic ALS

Mutations in the gene encoding Cu, Zn-superoxide dismutase (SOD1) are known to cause FALS.  Recently, we found that misfolded forms of the wild-type (WT)-SOD1 protein are associated with SALS, and exert the same toxic effect on axonal transport as FALS-linked mutant SOD1 proteins.  We are currently investigating the post-translational modifications of WT-SOD1 that cause it to misfold in vivo, and are developing aberrantly modified WT-SOD1 proteins, such as oxidized SOD1 (SODox), to study in vitro.  The properties of these SOD1 proteins are being investigated in the context of various cell biological and biophysical assays.

Investigating the pathogenic mechanism of FUS/TLS in neurodegeneration

Genetic variants in the gene encoding FUS/TLS, a nuclear RNA binding protein, have recently been linked to FALS.  Moreover, FUS pathology in the form of cytoplasmic aggregates has been detected in a spectrum of neurodegenerative disorders.  It is not clear whether FUS pathogenesis stems from a loss of normal nuclear FUS function, or from a gain of toxic function in the cytoplasm, and thus we are exploring both possible mechanisms.  We are investigating the pathogenic role of FALS-linked FUS in the following processes i) transcription, ii) axonal transport, and iii) stress-response (e.g., pathways that involve the formation of stress-granules).

In our lab and in collaboration with others, we employ cell biology, biochemistry, structural biology (e.g., NMR and X-ray crystallography), and mass spectrometry approaches for the investigations described above.