Dr. Zheng's research covers the neurotoxicology of heavy
metals with an emphasis on the role of brain barrier systems
in metal-induced neurotoxicity; biochemical and molecular
mechanisms of manganese (Mn)-induced neurodegenerative disorders;
and pharmacokinetics/toxicokinetics of drugs and toxic metals.
The concept of
a barrier between the blood and brain interface was originally
conceived in 1906. For nearly a century, researchers
have gradually come to realize that the brain barriers, namely
blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF)
barrier (BCB), not only act as the "gate-keeper" in
maintaining the chemical stability of the central nervous
system (CNS), but also actively participate in, among others,
brain ontogenesis, development, neuroendocrine regulation,
drug efflux and metabolism, as well as aging processes.
Dr. Zheng's laboratory at Columbia University has been conducting
the pioneer investigation in exploring contributions of brain
barriers in chemical-induced neurotoxicities.
His previous investigation indicates that the choroid plexus
avidly sequesters the toxic metal lead (Pb), manganese (Mn),
cadmium (Cd), and arsenic (As). Accumulation of Pb in the
blood-CSF barrier can lead to a decrease in CSF concentration
of transthyretin (TTR), which may, in turn, provoke lasting
neurodevelopmental deficits. Recent studies also suggest
that TTR plays an important role in amyloidogenesis, a key
step in pathogenesis of Alzheimer's disease.
Dr. Zheng has also conducted the studies on the mechanisms
of Mn-induced Parkinsonism, which has gradually become a
public health concern as Mn-containing organic compound is
currently used in gasoline for replacement of Pb in the US.
His work focuses on how Mn exposure alters brain Fe metabolism
by modulating the interaction between certain proteins and
mRNAs critical to Fe regulatory processes at blood-brain
barrier and blood-CSF barrier. The vigorous research led
by Dr. Zheng has helped create a new research field, which
is widely regarded as the Neurotoxicology of Brain Barriers.
With the continued support through the NIEHS RO1 mechanism,
Dr. Zheng has been able to establish the state-of-art facility
for brain barrier research in his laboratory, from in vivo
animal models to in vitro procedures and from in situ biophysiological
methods to molecular techniques.
More recently, Dr. Zheng's laboratory, by using a gene transfer
technique, has successfully innovated an immortal choroidal
epithelial cell line. Dr. Zheng's group aims to discover
the molecular mechanisms underlying toxic metal-induced neurotoxicity.
Dr. Zheng received his Ph.D. in Pharmacology/Toxicology
from University of Arizona with Dr. Vasken Aposhian in 1991.
He did his postdoctoral training with Dr. Glenn Sipes from
1991 to 1993. His original thesis research with Dr. Aposhian
at Arizona has led to his career in academia.
More interestingly, his rigorous training in Toxicology
with Glenn Sipes as well as the training program at Arizona
has made him the only Ph.D. in Toxicology at Columbia University
School of Public Health.
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