Suzie Chen, Ph.D.
Rutgers – Ernest Mario School of PharmacyEOHSI – Toxicology
Work Lab for Cancer Research Room 213 164 Frelinghuysen Road Piscataway NJ 08854 work
Work Phone: 848-445-7243work
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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 has been shown to be highly rearranged in a large number of human nonfamilial malignant melanomas. A combination of techniques were used to identify intron 3 of metabotropic glutamate receptor 1 (Grm1) as the gene 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. Mice with null mutations in Grm1 display reductions in hippocampal long term potentiation, and abnormalities of motor coordination and associative learning. 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. Co-localization of Grm1 and the melanocyte-marker Tyrp-1 was detected only in tumors and not in the normal counterparts. 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. Founder of Dct-Grm1 exhibited melanotic tumors on the tail at 7.5 months of age. High levels of Grm1 expression were observed in tail tumors but not in normal tail. Histopathological analysis showed these tumors to be very similar to those of TG-3. These results provide the compelling evidence suggesting the improtance of Grm1 signaling in melanocytic neoplasia.
Together with Dr. J. Goydos at CINJ, we begin to explore the potential role of the aberrant expression of Grm1 in human melanoma development and progression. Our data on human melanoma biopsy samples (7/19) showed expression of Grm1. Grm1 expression was not detected in two benign nevi and one normal skin samples. Similar analyses were also done with 18 human melanoma cell lines, 12/18 of these cell lines showed Grm1 expression, these results were confirmed by immunofluorescence. Co-localization of Grm1 and Tyrp1 (a melanocyte-specific marker) was detected only in lines that also showed Grm1 expression.
- Melanoma research
- Melanoma research from bench to the clinic.
- 2014 – present Council member of PanAmerican Society for Pigment Cell Research
- 2011 – present VA Oncology Study Section
- 2004 – present Member, NCI Special Emphasis Panel
- 2000 – present Planning and Review Committee for the Annual Retreat on Cancer Research
- 2004-2010 National Institute of Health Grant
- 2007-2012 National Institute of Health Grant
- 2009-2011 State of New Jersey Commission on Cancer Research Grant
- Eddy, K, Chen, S. Glutamatergic Signaling a Therapeutic Vulnerability in Melanoma. Cancers (Basel). 2021;13 (15):. doi: 10.3390/cancers13153874. PubMed PMID:34359771 PubMed Central PMC8345431
- Eddy, K, Shah, R, Chen, S. Decoding Melanoma Development and Progression: Identification of Therapeutic Vulnerabilities. Front Oncol. 2020;10 :626129. doi: 10.3389/fonc.2020.626129. PubMed PMID:33614507 PubMed Central PMC7891057
- Prokopi, A, Tripp, CH, Tummers, B, Hornsteiner, F, Spoeck, S, Crawford, JC, Clements, DR, Efremova, M, Hutter, K, Bellmann, L et al.. Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy. J Immunother Cancer. 2021;9 (1):. doi: 10.1136/jitc-2020-000832. PubMed PMID:33408092 PubMed Central PMC7789456
- Eddy, K, Chen, S. Overcoming Immune Evasion in Melanoma. Int J Mol Sci. 2020;21 (23):. doi: 10.3390/ijms21238984. PubMed PMID:33256089 PubMed Central PMC7730443
- Shah, R, Chen, S. Metabolic Signaling Cascades Prompted by Glutaminolysis in Cancer. Cancers (Basel). 2020;12 (9):. doi: 10.3390/cancers12092624. PubMed PMID:32937954 PubMed Central PMC7565600
- Bernard, A, Chevrier, S, Beltjens, F, Dosset, M, Viltard, E, Lagrange, A, Derangère, V, Oudot, A, Ghiringhelli, F, Collin, B et al.. Cleaved Caspase-3 Transcriptionally Regulates Angiogenesis-Promoting Chemotherapy Resistance. Cancer Res. 2019;79 (23):5958-5970. doi: 10.1158/0008-5472.CAN-19-0840. PubMed PMID:31611309
- Khan, AJ, LaCava, S, Mehta, M, Schiff, D, Thandoni, A, Jhawar, S, Danish, S, Haffty, BG, Chen, S. The glutamate release inhibitor riluzole increases DNA damage and enhances cytotoxicity in human glioma cells, in vitro and in vivo. Oncotarget. 2019;10 (29):2824-2834. doi: 10.18632/oncotarget.26854. PubMed PMID:31073373 PubMed Central PMC6497458
- Shah, R, Singh, SJ, Eddy, K, Filipp, FV, Chen, S. Concurrent Targeting of Glutaminolysis and Metabotropic Glutamate Receptor 1 (GRM1) Reduces Glutamate Bioavailability in GRM1+ Melanoma. Cancer Res. 2019;79 (8):1799-1809. doi: 10.1158/0008-5472.CAN-18-1500. PubMed PMID:30987979 PubMed Central PMC6469683
- Shin, SS, Jeong, BS, Wall, BA, Li, J, Shan, NL, Wen, Y, Goydos, JS, Chen, S. Participation of xCT in melanoma cell proliferation in vitro and tumorigenesis in vivo. Oncogenesis. 2018;7 (11):86. doi: 10.1038/s41389-018-0098-7. PubMed PMID:30425240 PubMed Central PMC6234219
- Filipp, FV, Birlea, S, Bosenberg, MW, Brash, D, Cassidy, PB, Chen, S, D’Orazio, JA, Fujita, M, Goh, BK, Herlyn, M et al.. Frontiers in pigment cell and melanoma research. Pigment Cell Melanoma Res. 2018;31 (6):728-735. doi: 10.1111/pcmr.12728. PubMed PMID:30281213 PubMed Central PMC6701837
Categories: Faculty, Toxicology, Member, Tox Member
Updated 9 months ago.