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oai:dspace.mit.edu:1721.1/1393182022-01-15T03:26:03Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022

White, Forest M. Stopfer, Lauren Elizabeth Massachusetts Institute of Technology. Department of Biological Engineering 2022-01-14T15:03:43Z 2022-01-14T15:03:43Z 2021-06 2021-10-27T16:33:59.544Z https://hdl.handle.net/1721.1/139318 Significant advancements in proteome-based analyses stem from innovations in the field of mass spectrometry (MS), an analytical method which allows for the sequencing, identification, and quantification of peptides and proteins in complex biological mixtures. MS enables a molecular and systems-wide understanding of the cell state, capturing post-translational modifications, protein turnover rates, protein-protein interactions, and other measurements that genetics cannot assess. Still, MS-based methods often require a compromise between reproducibility, quantitative accuracy, sensitivity, and depth of coverage, limiting their utility in research and translational settings alike. Here, I present a collection of MS-based platforms for targeted tyrosine phosphorylation signaling measurements and quantitative immunopeptidomics profiling, enabling novel biological findings in the field of cancer research. I describe how targeted tyrosine signaling assays can be leveraged to identify activated signaling pathways and assess immune infiltration in colorectal cancer. I also demonstrate how small molecules alter the peptide major histocompatibility complex repertoire in melanoma, and report copies-per-cell estimates of select treatment-modulated antigens using targeted MS, informing the development of targeted immunotherapies. Together, these findings highlight how innovations in MS-based methods can be used to advance a basic biology understanding of cancer and serve to demonstrate the clinical utility of using such assays to inform cancer therapy. Ph.D. Massachusetts Institute of Technology In Copyright - Educational Use Permitted Copyright MIT http://rightsstatements.org/page/InC-EDU/1.0/ Quantitative mass spectrometry-based approaches for characterizing the immunopeptidome and tyrosine phosphoproteome in cancer Thesis application/pdf Doctoral Doctor of Philosophy Publication unknown unknown <Publication xmlns="https://www.openaire.eu/cerif-profile/1.1/" id="9da28093-a092-4342-b010-271028304beb"> <Type xmlns="https://www.openaire.eu/cerif-profile/vocab/COAR_Publication_Types">http://purl.org/coar/resource_type/c_1843</Type> <Title>Quantitative mass spectrometry-based approaches for characterizing the immunopeptidome and tyrosine phosphoproteome in cancer</Title> <PublishedIn> <Publication> </Publication> </PublishedIn> <PublicationDate>2021-06</PublicationDate> <Authors> <Author> <DisplayName>Stopfer, Lauren Elizabeth</DisplayName> <Affiliation> <OrgUnit> </OrgUnit> </Affiliation> </Author> </Authors> <Editors> </Editors> <Publishers> <Publisher> <DisplayName>Massachusetts Institute of Technology</DisplayName> <OrgUnit /> </Publisher> </Publishers> <License>http://rightsstatements.org/page/InC-EDU/1.0/</License> <Abstract>Significant advancements in proteome-based analyses stem from innovations in the field of mass spectrometry (MS), an analytical method which allows for the sequencing, identification, and quantification of peptides and proteins in complex biological mixtures. MS enables a molecular and systems-wide understanding of the cell state, capturing post-translational modifications, protein turnover rates, protein-protein interactions, and other measurements that genetics cannot assess. Still, MS-based methods often require a compromise between reproducibility, quantitative accuracy, sensitivity, and depth of coverage, limiting their utility in research and translational settings alike. Here, I present a collection of MS-based platforms for targeted tyrosine phosphorylation signaling measurements and quantitative immunopeptidomics profiling, enabling novel biological findings in the field of cancer research. I describe how targeted tyrosine signaling assays can be leveraged to identify activated signaling pathways and assess immune infiltration in colorectal cancer. I also demonstrate how small molecules alter the peptide major histocompatibility complex repertoire in melanoma, and report copies-per-cell estimates of select treatment-modulated antigens using targeted MS, informing the development of targeted immunotherapies. Together, these findings highlight how innovations in MS-based methods can be used to advance a basic biology understanding of cancer and serve to demonstrate the clinical utility of using such assays to inform cancer therapy.</Abstract> <Access xmlns="http://purl.org/coar/access_right" > </Access> </Publication>