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Suzie
Chen, PhD |
| Title: Professor |
| Affiliation: Rutgers, The State University of NJ |
| Department:
Chemical Biology |
| Research Interests:
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Molecular
mechanisms of melanoma development using a
transgenic mouse model system. Involvement
of Grm1, a G-protein-coupled receptor in
control of cell growth and cell
differentiation.
The main interest in my laboratory is to
study the molecular mechanisms of melanoma
development using a line of transgenic mice
(TG-3) generated in my lab several years
ago. From mapping studies, we have
determined that about 70 kb of host
sequences have been deleted by the insertion
of the transgene. The host DNA had been
deleted from a region of mouse chromosome
10, which is syntenic to the long arm of
human chromosome 6. This region of human
chromosome 6 is highly rearranged in a large
number of human nonfamilial malignant
melanomas. A combination of techniques was
utilized to identify intron 3 of
metabotropic glutamate receptor 1 (Grm1) as
the region disrupted by the insertion of the
transgene. The metabotropic glutamate
receptors (mGluRs) belong to a family of
seven transmembrane-domain, G-protein
coupled receptors (GPCRs).
Expression of mGluRs is usually restricted
to neuronal cells, but the signaling
pathways activated by these receptors are
widely distributed in both neural and
non-neural cells. In the TG-3 line, we
showed that Grm1 is expressed only in ear
tumors, but not normal ear as demonstrated
by semi-quantitative RT-PCR, Western
immunoblots, immunofluorescence and
immunohistochemistry. Based on these
results, a new transgenic line was generated
with targeted Grm1 expression to melanocytes,
by using Grm1 cDNA under the melanocyte-specific
Dct (dopachrome tautomerase) promoter. This
new transgenic line showed similar tumor
development/progression as those of TG-3.
These results provide the compelling
evidence suggesting the importance of Grm1
signaling in melanocytic neoplasia.
Together with Dr. J. Goydos at CINJ, we have
identified aberrant expression of GRM1 in a
subset of human melanoma biopsy samples
(40%). GRM1 expression was not detected in
benign nevi and normal skin samples.
Our future research interests include
studies on the molecular mechanisms in
deregulation of GRM1 expression in human
melanoma and explore the potential of using
GRM1 as a therapeutic target for the
treatment of late-stage melanoma.
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