Sucharita Dutta (Presenter)
EVMS
Bio: I am currently employed with Eastern Virginia Medical School. I manage the mass spectrometry facility at the Leroy T. Canoles Cancer Research Center. As part of the cancer center, I perform OMICS experiments including proteomics, lipidomics and metabolomics on a high resolution accurate mass platform.My research component at EVMS involves employing a translational research workflow on high resolution accurate mass instrumentation for detection of pathogen induced cancer in a human T-cell leukemia virus type 1 disease model.
Authorship: Sucharita M. Dutta1, Scott Peterman2, Amol Prakash3, Arjun Poddar1, John Semmes1
1Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, Virginia, U.S.A. 2Thermo Fisher Scientific, San Jose, CA 3Optys Technologies, Boston, MA
| Short Abstract Exosomes are micro vesicles secreted by the cell membrane and their contents could be used as an effective means to detect many different cancers. By profiling the Exosome cargo from blood samples of patients from different stages of Leukemia we are exploring for Leukemia specific biomarkers that are secreted into the blood. An integrated profiling of the microRNA, messengerRNA and protein content of the exosome would lead to unique signatures that make exosomes ideal for cancer detection. Here, we review the unique proteomic contents of exosomes originating from Leukemia cancer cells as well as their functional effects to promote tumor progression. |
Long Abstract
The Human T-Cell Leukemia Virus Type 1 (HTLV-1) is the causative factor for the development of an aggressive lymphoma, Adult T-cell Leukemia (ATL). The diversity in clinical features and significant differences in outcome have led to the sub-classification of ATL differentiated into aggressive form of the disease on one end of the spectrum (with extremely poor prognosis) to the asymptomatic version of the disease. We capitalized on two aspects of ATL biology to identify biomarkers for early detection and diagnosis based on 1) HTLV-1 infected cells have developed mechanisms to avoid immune clearance and 2) fractionate out circulating exosomes from the serum samples that serve as repositories for infection/tumor immunity and can be used to enrich for ATL disease specific biomarkers. Exosomes are a specific class of extracellular vesicles that are emerging as major players in cell-cell communication with noted impact on immune regulation and cancer progression.
Our translational workflow involved standard DDA experiments followed by more in-depth pSMART data acquisition methodologies for the most comprehensive global profiling of proteins from exosome samples to exhaustively mine for proteins that show functional significance via pathway analysis. In our approach we use novel algorithms developed by Optys Technologies to study differential expression for several candidate biomarker proteins and their differential post-translational modifications to increase our confidence in feature selection. We have employed both unbiased and directed strategies to identify an entire panel of proteins for disease stratification. In addition to providing unprecedented analysis of glycosylation and other post-translational modifications; we are currently testing application of our protein panels to serum versus exosomes to facilitate the development of more effective diagnostic and therapeutic strategies to ATL.
References & Acknowledgements:
1) Saba, J.; Dutta, S.M.; Hemenway, E.; Viner, R. “Increasing the Productivity of Glycopeptides Using Higher Energy Collision Dissociation-Accurate Mass Product Dependent-Electron Transfer Dissociation” Int. Journal of Proteomics. 2012 Volume 2012, Article ID 560391
2) Scott, N. E.; Kinsella, R. L.; Edwards, A. V.; Larsen, M. R.; Dutta, S.; Saba, J.; Foster, L. J.; Feldman M. F. “Diversity Within the O-linked Protein Glycosylation Systems of Acinobacter Species” Mol Cell Proteomics. 2014 Sep;13(9):2354-70. doi: 10.1074/mcp.M114.038315.
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