Dr. Rosario has published pivotal papers using the novel bioinformatics pipeline she developed to determine which of 114 metabolic pathways are transcriptionally dysregulated between any two conditions.
This pipeline has been utilized to identify novel points of metabolic leverage in several different cancer settings including prostate and ovarian cancer, among others.
The metabolic pipeline
- RNA sequencing data is obtained from biomaterials (A) from multiple conditions (e.g., tumor and normal tissue across multiple cancer types).
- Differential transcriptomics analysis (B) is then utilized to highlight disregulated metabolic pathways, by assigning metabolic scores (C) that can be visualized between all conditions (D), integrated with other types of -omics data (E) and modeled within a pathway (F).
- This information can then be utilized for informing new, more targeted sequencing (H) and -omics approaches.
A recent publication has highlighted a novel and critical role for IDO1 inhibition and tryptophan/kynurenine metabolism in ovarian cancer immunology, and many of these principles have been translated to recently submitted papers or papers in revision, which detail critical metabolic pathways of interest in different disease sites.
Immune function in obese cancer patients
Recently published work from Dr. Rosario’s group, along with her collaborators, focuses on the metabolic etiology that underlies immune function in obese cancer patients, specifically in regulatory T cell populations in lung cancer and macrophages/monocytes in gastrointestinal cancer, further mediating uninhibited tumor cell growth.
Preliminary data generated have implied that much of this biology hinges on the preferential shunting of Acetyl CoA metabolism and tryptophan metabolism, respectively. The differences in these two sites further assert the need for pipelines to assess, integrate and build metabolic pathways in a personalized way.
Cancer Moonshot: Immuno-Oncology Translational Network
Mechanistically, Dr. Rosario and her collaborators in the Immuno-Oncology Translational Network (IOTN) and Acquired Resistance to Therapy Network (ARTNet) have been working to integrate genomic, transcriptomic, proteomic and metabolomics data to better understand the metabolic pathway alterations involved in different disease states, including those induced by racial differences, and those altered specifically in immune cell populations.
Further, in Dr. Rosario’s role with the Bioanalytics, Metabolomic and Pharmacokinetics Shared Resource, she has contributed to the development and understanding of numerous assays, including the related metabolites.
Connect with the Rosario Lab
Email: Spencer.Rosario@RoswellPark.org
Phone: 716-845-1300 ext. 6271
Department of Biostatistics and Bioinformatics
Roswell Park Comprehensive Cancer Center
Elm and Carlton Streets
Buffalo, NY 14263