Faculty / Research
Emily I. Chen, PhDAssistant Professor
Scientific Director: Proteomics Center of Stony Brook University School of Medicine
Ph.D., University of California, San Diego, School of Medicine
B.S., University of California, San Diego
(631) 444-3134 email@example.com
Cancer Metastasis: Mechanisms of Organ-Specific Metastasis in Human Breast Cancer and Protein Analysis: Shotgun Proteomics
Metastasis to distant organs is a highly specific process. The origin of the primary tumor seems to determine which distant organs will be colonized. For example, preferred organs for breast cancer metastasis are lymph nodes, bone, lung, brain, and liver. Typically, research on metastasis is performed based on in vivo assays in small animal models, as no single in vitro assay can recapitulate this process. Assays are normally divided into ones for experimental metastasis and ones for spontaneous metastasis. Experimental metastasis is analyzed by injecting tumor cells into the circulatory system and therefore measures only the last steps of the metastatic process, success in colonization of a secondary site. We have employed this assay to obtain brain, lung, and bone metastatic variant cancer cells derived from the original heterogeneous primary breast tumor cell line. Using this experimental metastasis model, we have found changes in the tumorigenecity of the cancer cells that successfully proliferate at sites of metastasis. Specifically, the genes and proteins expressed in those cells differ in part from those expressed by primary tumor cells. Moreover, the changes in expression differ accordingly to the individual metastatic site. These data indicate that the tumor cells are selected for or adapt to the new environments by initiating a unique program of transcriptional and translational regulation. Strikingly, we have found that this reprogramming of genes and protein expression includes factors that enable the cancer cells to respond to growth signals already present in the specific local environment of the secondary tissue.
Metastatic Cancer Stem Cells and Organ Specific Metastasis
Recent studies have described a small population of self-renewing and multipotent cells within tumors termed “cancer stem cells” that have been proposed to be the source of primary tumors and secondary metastases in many types of cancer. In my laboratory, studies are proposed to address two questions: i) is the phenotype of invasion and metastasis uniquely connected to the tumor stem cell phenotype? ii) does the tumor stromal niche act as a constituent of a feedback mechanism with tumor stem cells to control their growth? Ultimately, we hope to generate new molecular insights of the metastatic cancer stem cells and generate novel therapeutic approaches to eradicate the metastatic subpopulation of breast tumor.
Bridging the Gap between Biology and Mass Spectrometry-Based Proteomics
During the last decade, the field of proteomics has evolved rapidly to overcome technical limitations to improve the dynamic range and reproducibility of large-scale proteomic analyses. In particular, advances in mass spectrometry instrumentation and bioinformatics for “bottom-up” or “shotgun” proteomic approaches have been at the core of new developments to meet the challenge of biological complexity. These methods are striving to provide a more comprehensive view of the multi-factorial processes occurring during normal development or disease progression. Our laboratory and the SOM Proteomics Center have been focusing on developing mass spectrometry-based proteomics technology to measure changes in protein abundance, post-translational modifications, and protein-protein interactions at the proteome scale. Some of these technical advances developed in my laboratory include metabolic labeling of inbred laboratory mice using stable isotope (15N) for studying human diseases using transgenic mouse models, large-scale proteome profiling using FFPE human tissues for biomarker discovery, and mass spectrometry-compatible protein extraction procedures for global analysis of difficult to obtain biological samples. We also have active collaborations to characterize post-translational protein modifications such as phosphorylation, ubiquitinylation, acetylation, and etc. A list of mass spectrometers available in my laboratory and services provided by the SOM Proteomics Center can be found in the following website.
Dr. Chen received her Ph.D. degree from the Department of Molecular Pathology at the University of California, San Diego in 2002. Then, she pursued her postdoctoral training at the Scripps Research Institute in Dr. John Yates’ laboratory. Currently, she is a faculty member in the Department of Pharmacological Sciences and the Scientific Director of the Proteomics Center at the Stony Brook University School of Medicine. Using the cutting-edge mass spectrometry-based proteomic techniques, her current research focuses on elucidating mechanisms of tissue-specific breast cancer metastasis and identifying protein targets to eradicate the growth of distal breast cancer metastasis. Her laboratory is also developing new proteomics techniques to characterize post-translational modifications of proteins and to perform molecular analysis of archived FFPE tissues from human patients.
Cancer Related Publications:
- Chen E.I., Florens L, Axelrod F.T., Monosov E, Barbas CF 3rd, Yates J.R. III, Felding-Habermann B, Smith J.W. Maspin alters carcinoma proteome, (2005) The FASEB Journal, published online April 27, 2005.
- Blancafort P, Chen E.I., Gonzalez B, Bergquist S, Zijlstra A, Guthy D, Brachat A, Brakenhoff R.H, Quigley JP, Erdmann D, and Barbas CF 3rd. Genetic Reprogramming of tumor cells by zinc finger transcription factors, (2005) Proc Natl Acad Sci USA 102(33): 11716-21.
- Chen E.I. and Yates JR 3rd. Maspin and Tumor Metastasis, (2006) IUBMB Life, Jan; 58(1):25-9.
- Chen E.I., Hewel J, Krueger JS, Weber MR., Tiraby C, Kralli A, Becker K, Yates JR 3rd, Felding-Habermann B, Adaptation of Energy Metabolism in Breast Cancer Brain Metastasis, (2007) Cancer Research, Feb 15;67(4):1472-86.
- Chen E.I., Yates JR 3rd, Cancer Proteomics by Quantitative Shotgun Proteomics, (2007) Molecular Oncology, 1:144-159.
- Louie E., Nik S., Chen J.S., Schmidt M, Bo Song, Seonhye Park, Pacson C., Chen X.F., Jingfang Ju, and Chen E.I., Identification of a Stem-Like Cell Population By Exposing Metastatic Breast Cancer Cell Lines to Repetitive Cycles of Hypoxia and Reoxygenation, (2010), Breast Cancer Research, Nov; 12(6):R94.
- Beliveau A., Mott J.D., Lo A., Chen E.I., Koller A.A., Yaswen P., Muschler J., and Bissell M.J., Raf-induced MMP9 Disrupts Tissue Architecture of Human Breast Cells in Three-Dimensional Culture and is Necessary for Tumor Growth in vivo. (2010), Genes & Development, Dec 15;24(24):2800-11.
Proteomics Related Publications:
- Chen E.I., Hewel J, Felding-Habermann B., Yates JR 3rd. Large Scale Protein Profiling by Combination of Protein Fractionation and MudPIT, (2006) Molecular & Cellular Proteomics, Jan; 5(1):53-6.
- Chen E.I., Cociorva D., Norris J.L., Yates JR 3rd, Optimization of Mass Spectrometry Compatible Surfactants for Shotgun Proteomics, (2007) J of Proteome Res., Jul;6(7):2529-38.
- Chen E. I., McClatchy D., Park S.K., Yates JR3rd, Comparisons of Mass-Spectrometry Surfactants for Global Analysis of the Mammalian Brain Proteome, (2008) Analytical Chemistry, Nov;80(22):8694-701.
- Carvalho P.C., Fischer J.SG., Chen E.I., Yates JR 3rd , PatternLab for proteomics: a tool for differential shotgun proteomics, (2008), BMC Bioifnormatics, 9:316.
- Carvalho P.C., Fischer J.S., Chen E.I., Domont G.B., Carvalho M.G., Degrave W.M., Yates JR 2rd, Barbosa V.C., GO Explore: A gene-ontology tool to aid in the interpretation of shotgun proteomics data, (2009), Proteome Sci., Feb 24; 7:6.
- Nicholas M. Andronicos, Chen E.I., Nagyung Baik, Hongdong Bai, Mark P. Kamps, John R. Yates III, Robert J. Parmer, and Lindsey A. Miles, Proteomic-Based Discovery of A Novel, Structurally Unique, and Developmentally Regulated Transmembrane Plasminogen Receptor (2010), Blood, Feb 18; 115:1319-30.
Current Laboratory Members:
Graduate Student (Pharmacological Sciences) - Elizabeth Louie
Senior Research Assistant - Marlies Schmidt
Research Assistant - Alexandra Coomes, B.S., Xiu Fang Chen, B.S.
Undergraduate Students - Jennifer Ng, Kate Ke, Vivian Liang
Past Laboratory Members:
Sara Nik - master program at the Columbia University Graduate School of Arts and Sciences