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Alice Y.-C. Liu
Professor
Rutgers University
Cell Biology and Neuroscience
Nelson Labs Room B303
Rutgers University
Piscataway. NJ 08855
(732) 445-2730
FAX - 5870
liu@biology.rutgers.edu |
Stress. aging. and molecular chaperones
Our primary research interest is to better
understand the biology of aging and age-related decrease in stress resistance.
While aging is a complex process with multiple environmental and genetic inputs. there is nevertheless good evidence that oxidation and oxidative damage
contribute to the aging process and that genes and cell physiology that confer
stress resistance. including resistance to oxidative stress. prolong life-span.
One of the major
cellular effect of stress is activation of the heat shock transcription factor 1
(HSF1) and induction of the heat shock transcriptional response. In our
research. we showed that induction of the heat shock response (from the
activation of HSF1 to the production of HSPs) becomes attenuated in aging human
diploid fibroblasts. An attenuated response to stress has also observed in
aging animal model systems and in cell culture systems derived from them.To
better understand the mechanism of the age-dependent dysfunction of HSF1. we
evaluated the role of oxidation-reduction in the regulation of HSF1.Experiments done in vitro provided clear and convincing evidence that
that redox is an important mechanism in regulating the structure and function of
HSF1. and that oxidation and disulfide crosslinking of cysteines is an
off-switch for the activation and trimerization of hHSF1. Our current research
effort includes: (1) the use of HSF1 minus cells (immortalized murine embryo
fibroblasts derived from hsf1 knockout animals) to test for regulation and
function of the wild type and cysteine-site-specific mutants of HSF1 in a
cellular context. (ii) analysis of the effects of redox modifiers in the
cellular regulation and function of HSF1. and (iii) determining the
pathophysiologiclal changes of HSF1 in cell aging and upon oxidative stress. Our long range goal is to better understand the relationship of redox-dependent
protein modification. transcription factor regulation. and the molecular basis
of transcription factor dysfunction under a variety of physiological and
pathophysiological conditions including aging. In so doing. we are hopeful
that our work will contribute to the emerging concept of redox as a versatile
epigenetic mechanism by which cells regulate important biological processes.
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