Wei-Hua Lee, M.D., Ph.D.
Associate Professor
Office:
(317) 274-7116
Email:
whlee@iupui.edu
My main interest is to
understand the role of neurotrophic factors during brain development. The
development of a mammalian brain is among the most remarkable feats accomplished
during embryogenesis. In humans, immature neural cells are formed as early as
two weeks after conception. Thereafter, these cells proliferate, differentiate
and migrate to their final destinations, while forming synaptic networks that
pave ways for the functional maturity of the brain. To date, we do not know how
the structures and functions of the brain develop. We do know, however, that
brain development requires growth factors which play leading roles in the timing
and organization of brain cells. The main interest of our laboratory, therefore,
is to study how these growth factors interact with brain cells during their
structural and functional maturation. In particular, we have focused on the role
of insulin-like growth factor I (IGF-I) in brain development, acute injury and
chronic neurodegeneration.
Following research projects are currently underway in our laboratory:
The functional role of IGF-I during CNS development. We are investigating the
biological effects of IGF-I on the proliferation, differentiation, function, and
survival. We are also interested in the signaling mechanisms that mediate
IGF-I’s pleiotrophic activity in response to a variety of stimuli. Information
derived this basic research offers us valuable clues for future use of growth
factors in treat neuronal injury and neurodegeneration.
Can IGF-I protect young neurons from hypoxic-ischemic neuronal injury? Cerebral
hypoxia-ischemia (HIE) remains a leading cause of severe brain damage in
newborns, which often results in devastating disabilities, such as cerebral
palsy, mental retardation, and epilepsy. To date, no treatment is yet available
to help the damaged brain and improve the prognosis and well being of these
children. IGF-I reduced neuronal loss and improved somatosensory functional
recovery in animal models of HIE. Currently, we are studying the molecular and
cellular mechanisms of IGF-I’s neuroprotection against hypoxic-ischemic injury
in vitro using primary neuronal culture and in vivo using a rodent model of HIE.
Can IGF-I promote mature neurons to survive neurodegeneration? IGF-I is also an
excellent candidate in rescuing neurons from degeneration in genetic diseases,
such as cerebellar ataxia, motor neuron diseases and Alzheimer’s disease.
Currently, we are investigating the molecular mechanisms as well as the
therapeutic potential of IGF-I in the treatment of hereditary cerebellar ataxia.
Publications:
Wang X-H, Jixian Deng, Jin Zhong, and Lee W-H. (2003) Activation of
Hypoxia-Inducible Factor-I in the Rat Brain after Hypoxia Preconditioning:
Potential Role of Insulin-Like Growth Factor-1 in Hypoxia Tolerance. Pediatric
Research (in press)
Zhong J, Deng J-X, Ghetti B. Lee W-H. (2002) Inhibition of Insulin-Like Growth
Factor I’s Activity Contributes to the Premature Apoptosis of Cerebellar Granule
Neuron in Weaver Mutant Mice: An In Vitro Analysis. Journal of Neuroscience
Research 70:36-45
Shen W-H, Yang X-L, Boyle D.W., Lee W-H, and Liechty E.A. (2001) Effects of
intravenous insulin-like growth factor-I and insulin administration on
insulin-like growth factor binding proteins in the ovine fetus. J Endocrinology
171:143-151
Cheng CM, Reinhardt RR, Lee W-H, Joncas G, Patel SC and Bondy CA (1999) IGF-I
regulates developing brain glucose metabolism. PNAS 97(18):10236-10241
Zhang W., Ghetti B., Yanglin Yang and Lee W.-H. (1999) Alteration of IGF system
gene expression during the postnatal development of pcd mice. Journal of
Endocrinology 163:191-198
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