Aging
Stress and Memory
Why does memory decline with Aging?
How does stress affect memory?
Our goal is to prevent age related cellular decline and
restore function.
Research
Interest
Polyphenolic
neutraceuticals
Cylic polyphenols, such as the compounds Fisetin,
Resverotrol, Curcumin and Proanthocyanidin, may impact
directly on the glucocorticoid stress response pathway
and that this accounts for many of the wide range of
activities attributed to these compounds.
Polyphenolic neutraceuticals have been demonstrated to
be neuroprotective and enhance cognition. These
compounds modulate multiple cellular pathways and
activities. Many of these compounds exhibit antioxidant
activity and maintain mitochondrial function under
oxidative stress. These compounds also exhibit
anti-inflammatory activity, anti-apoptotic, reduce
edema and enhance neurogenesis.
Our laboratory was the first to demonstrated that
curcumin can increase hippocampal neurogenesis, counter
impaired cognition and increase neural plasticity.
We have also identified additional compounds that
appear to behave similarly to curcumin in the brain,
trans-resveratrol and low molecular weight
proanthocyanidins. It is anticipated that these
compounds will exhibit similar affects on neurogenesis,
cognitive enhancement and increased neural plasticity.
Based on the structures of these three compounds an
additional three lead compounds are currently being
tested in an anti-depression model. It should be
emphasized that all of these compounds are capable of
activating or inhibiting multiple cellular pathways.
Molecular
Computational Modeling
We are
developing computation models that integrate with our
in vivo and in vitro experimental systems. We have
built an improved model for the signaling molecule
Sonic hedgehog (Shh). Sonic hedgehog is a well-studied
signaling protein involved in vertebrate organogenesis,
particularly brain and limb organization, and more
recently implicated in the development of cancerous
tumors and neurogenesis. Our model incorporates both
the established functionality of pathway components,
such as Shh acting as a ligand for the membrane protein
Patched, as well as recent experimental results
indicating novel pathway interactions, such as vitamin
D3 transport and its binding to the membrane protein
Smoothened. The result is that our model reflects the
most current understanding of the dynamics of the Shh
system and predicts pathway behavior that is supported
by recent models of morphogen signal transduction and
neurogenesis.
Biological Engineering
Protein
Engineering
Optogenetics
Optical
Therapeutics
We are
currently moving into the area of optogenetics for the
control of epilepsy and into an area that we term
optical therapeutics with the creation of chimeric
receptors that can be used to isolate, monitor and
experiment on G protein coupled receptor pathways, our
initial project will focus on the estrogen receptors
and the cross talk between the rapid (G-protein coupled
receptor) and the genomic (nuclear hormone receptor)
signaling pathway. The objective of the proposed
research is to show that our understanding of the
dynamic interaction between signaling pathways can be
dramatically expanded through the use of biological
engineering and computational modeling.
Stress Hormones and
Neural Progenitors
Modulating the glucocorticoid proliferative response of
neural progenitors in vivo. Glucocorticoids inhibit
neural progenitor proliferation and play an unknown
role in the determination of cell fate. This is an
ongoing project where we are using engineered proteins
to modulate the glucocorticoid response in neural
progenitor cells.
