Research in the Chen laboratory mainly focuses on three areas:
(1) Mechanisms of Metastasis
Metastasis accounts for more than 90% of cancer-related deaths and yet remains one of the least understood aspects in cancer biology. One objective in our research is to identify mechanisms of metastasis and vulnerability of metastatic cells. We are among few groups that generate mouse models of metastatic prostate cancer based on prostate epithelium-specific inactivation of Pten. By performing integrative omics analyses of tumors from localized and metastatic mouse models, we aim to reveal transcriptional, translational and metabolic mechanisms that drive metastatic disease. Additionally, by conducting preclinical studies of drugs targeting vulnerability of metastatic cells, we hope we can find new strategies to prevent or slow the cancer spread in mice, and maybe eventually translate into the clinic.
(2) Lipid Metabolism and Cancer
Cancer cells are known to undergo metabolic reprogramming to support their rapid proliferation and growth. One of the most frequently dysregulated metabolic pathways in cancer is the activation of de novo lipogenesis. Our recent studies suggest that co-activation of the PI3K/AKT and MAPK pathways converges their oncogenic functions through SREBP-dependent lipogenic program, and that lipids obtained through de novo lipogenesis or dietary uptake may provide a cell-intrinsic signal promoting the aggressiveness of cancer. A current focus in the lab is to identify key genes and pathways that mediate lipid-driven tumorigenesis and to establish the molecular mechanisms connecting obesity and aggressive cancer.
(3) PTEN/PI3K/AKT and MAPK Signaling in Cancer
PTEN/PI3K/AKT and MAPK signaling pathways govern a variety of biological processes, including cell survival, proliferation, growth and metabolism. They are the most commonly altered pathways in human cancer and their cross-talk is also of key importance in the regulation of tumorigenesis. We have recently revealed a PP1α-PML molecular network that is genetically altered in human cancer towards aberrant MAPK activation in PTEN loss/PI3K-AKT driven cancers. Our studies are now focused on developing optimal combinatorial therapies that target different components of the pathway to combat human cancer.
- Mendez, L, Chen, M, and Pandolfi, PP. "Molecular Genetics of APL." In Acute Promyelocytic Leukemia A Clinical Guide, 41-53.: Springer, April 25, 2018. (Chapter)
- Yeh, S, Chen, M, Ni, J, Yin, Y, Chang, E, Zhang, M, and Wen, X. "Functions of estrogen receptor in prostate and prostate cancer." In Prostate Cancer Basic Mechanisms and Therapeutic Approaches, 293-313.: World Scientific, 2005. (Chapter)
- Chen, M, Huang, J "The Expanded Role of Fatty Acid Metabolism in Cancer: New Aspects and Targets." Precision Clinical Medicine2019 Sep;2(3):183-191
- Lee YR, Chen M, Lee JD, Zhang J, Lin SY, Fu TM, Chen H, Ishikawa T, Chiang SY, Katon J, Zhang Y, Shulga YV, Bester AC, Fung J, Monteleone E, Wan L, Shen C, Hsu CH, Papa A, Clohessy JG, Teruya-Feldstein J, Jain S, Wu H, Matesic L, Chen RH, Wei W, Pandolfi PP.Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway.Science 2019 May 17;364(6441) doi: 10.1126/science aau0159. PubMed PMID: 31097636
- Chen M, Zhang J, Berger AH, Diolombi MS, Ng C, Fung J, Bronson RT, Castillo-Martin M, Thin TH, Cordon-Cardo C, Plevin R, Pandolfi PP.Compound haploinsufficiency of Dok2 and Dusp4 promotes lung tumorigenesis.J Clin Invest 2019 Jan 2 129 (1) 215-222 doi: 10.1172/JCI99699. Epub 2018 Nov 26. PubMed PMID: 30475228; PubMed Central PMCID: PMC6307955.
- Lee, Y-R, Chen, M, and Pandolfi, PP. "The functions and regulation of the PTEN tumour suppressor: new modes and prospects." Nature Reviews. Molecular Cell Biology 19, no. 9 (September 2018): 547-562. (Review)
- Chen M, Zhang J, Sampieri K, Clohessy JG, Mendez L, Gonzalez-Billalabeitia E, Liu XS, Lee YR, Fung J, Katon JM, Menon AV, Webster KA, Ng C, Palumbieri MD, Diolombi MS, Breitkopf SB, Teruya-Feldstein J, Signoretti S, Bronson RT, Asara JM, Castillo-Martin M, Cordon-Cardo C, Pandolfi PP.An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer. Nat Genet. 2018 Feb;50(2):206-218. doi: 10.1038/s41588-017-0027-2. Epub 2018 Jan 15. PubMed PMID: 29335545.
- Chen, M, and Pandolfi, PP. "Preclinical and Coclinical Studies in Prostate Cancer." Cold Spring Harbor Perspectives in Medicine 8, no. 4 (April 2, 2018). (Review)