Section: Research

Daryl Bosco, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Neurology

Other Affiliation(s):
   Biochemistry and Molecular Pharmacology

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 an emphasis on amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease.  Approximately 10% of ALS cases are inherited through Mendelian genetics, whereas the vast majority (~90%) of cases are 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 sporadic ALS (sALS) pathogenesis.

Investigating protein mis-function associated with neurodegenerative disease

Mutations in the gene encoding Cu, Zn-superoxide dismutase (SOD1) are known to cause inherited, or familial, forms of ALS (fALS). We are currently investigating the hypothesis that post-translational modifications to the wild type SOD1 protein cause it to adapt a conformation similar to the mutant SOD1 proteins, and that this process is involved in some sporadic forms of the disease.  For example, oxidation of SOD1 WT (SODox) causes this protein to mimic the fALS-associated mutants.  The effect of SODox compared to mutant SOD is being studied in the context of various biological assays, including axonal transport and programmed cell death.  In addition, we are employing biophysical methods to i. structurally characterize SODox, and ii. identify small molecules that can stabilize oxidized SOD1.

Although several genes involved in fALS have been identified, many more gene variants are awaiting discovery. In collaboration with the genetics group in the Cecil B. Day laboratory directed by Dr. Robert H. Brown, Jr., we are characterizing fALS associated gene variants at the protein level. Investigation of these ALS-associated protein mutations, both in vivo and in vitro, continues to be instrumental to the field’s understanding of ALS pathogenesis.

We routinely employ molecular biology, cell biology, biochemical, and biophysical techniques for the investigations described above.

Office: LRB 603
Phone: 508-334-3035
E-mail: Daryl.Bosco@umassmed.edu
Keywords: Biophysics, Biochemistry, ALS, protein chemistry, sporadic neurodegeneration

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