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Lori White,
PhD |
| Title: Assistant Professor |
| Affiliation: Rutgers, The State University of NJ |
| Department:
Biochemistry & Microbiology |
| Research Interests:
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The focus of my laboratory is
to investigate the molecular mechanisms of
xenobiotic exposure and to link these
molecular changes to xenobiotic-induced
pathologies. The polycyclic aromatic
hydrocarbon (PAH)
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
is a byproduct of industrial combustion
processes. Exposure results in a variety of
pathologies in humans, including alterations
in the immune and neurological systems,
liver dysfunction, and increases in bladder
and skin cancer. It is believed that these
pathologies are mediated by TCDD binding to
the AhR (aryl hydrocarbon receptor) which
heterodimerizes with Arnt to function as a
transcription factor and alter gene
expression. Although this pathway has been
well characterized, it is unclear how TCDD
activation of the AhR pathway results in the
pathological effects of exposure. Using skin
as a model system, we aim to identify the
molecular pathways that are involved in
mediating PAH-induced pathologies, and to
better understand the role these chemicals
play in skin carcinogenesis. One area of
interest is to identify biologically
relevant targets of the AhR/Arnt pathway. To
this end, we have shown that exposure to
TCDD results in an increase in expression
and activity of matrix metalloproteinases in
normal human keratinocytes. These enzymes
mediate the degradation of the extracellular
matrix and basement membrane proteins during
processes of tissue remodeling and cell
migration, and inappropriate expression of
these enzymes is associated with tumor
metastasis. Another project is aimed at
understanding the regulation of an AhR
responsive gene, cytochrome p-450 1B1
(CYP1B1). CYP1B1 is a monoxygenase that
metabolizes xenobiotic compounds and
endogenous steroids to carcinogenic
compounds. We have recently found that
expression of this gene is influenced by
cell-cell interactions in murine
keratinocytes. By utilizing both human and
mouse model systems, we aim to gain a better
understanding of the molecular mechanisms
that are important for PAH-induced
carcinogenesis in skin. |
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