My research group studies fundamental processes in cell biology that drive age-related
neurodegenerative disorders. We employ a multi-system approach to rapidly identify, test,
and validate hypotheses. Early discovery takes place in
Drosophila, a model organism that is well-suited for investigating
issues of causality in disease processes. We complement our
Drosophila work with comparative
analyses in postmortem human brain to ensure that our findings are relevant to
focus of the laboratory is on tauopathy. Tauopathies, including Alzheimer’s
disease, are characterized by the deposition of tau protein aggregates in the
brains of affected individuals. Motivated by my previous work, which identified
relaxation of heterochromatic DNA as a novel disease mechanism in Alzheimer’s
disease and related tauopathies, we are currently investigating:
of nucleoplasmic reticulum expansion (Figure 1) in tauopathy in regard to
nucleocytoplasmic transport and nuclear calcium signaling
element and piRNA misregulation as a consequence of heterochromatin relaxation
Frost B, Bardai FH, Feany MB (2015) Lamin dysfunction mediates neurodegeneration
Current Biology, In press.
Frost B, Gotz J, Feany M (2015) Connecting the dots between tau dysfunction and neurodegeneration. Trends in Cell Biology, 25(1):46-53.
Frost B, Peng S, Yang Y, Park P,
Feany M (2014)
p53 prevents neurodegeneration by regulating synaptic genes. PNAS, 111(50):18055-60. PMCID:
Frost B, Hemberg M, Lewis J,
Feany M (2014)
Tau promotes neurodegeneration through global chromatin relaxation. Nature Neuroscience,
17(3):357-66. PMCID: PMC4012297. (See also accompanying News and Views in same
Frost B, Diamond MI (2010) Prion-like mechanisms in neurodegenerative diseases. Nature Reviews Neuroscience, 11(3)155-9. PMCID: PMC3648341.
Frost B, Diamond MI (2009) The expanding realm of prion phenomena in neurodegenerative disease. Prion, 3(2)74-7. PMCID: PMC2712602.
Frost B, Jacks RL, Diamond MI
Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem., 284(19):12845-52. PMCID:
Frost B, Ollesch J, Wille H,
Diamond MI (2009)
Conformational diversity of wild-type Tau fibrils specified by templated conformation change. J Biol
., 284(6):3546-51. PMCID: PMC2635036.