Veronica Anania (Presenter)
Genentech, Inc.
Bio: I joined Genentech in 2011 as a postdoctoral researcher to investigate post-translational modifications and to identify biomarkers of cell death using mass spectrometry (MS) based methods. In 2014 I was hired as a Scientist in Biomarker Development to lead a group focused on applying MS-based approaches to interrogate biomarker hypotheses in our clinical programs. Currently my group is utilizing targeted and discovery MS approaches to develop multiplexed panels of peptide or lipid biomarkers to measure changes in disease. We aim to identify noninvasive biomarkers to help inform treatment decisions and to monitor disease activity and progression. We hope these analytical approaches will allow us to make clear decisions regarding therapeutics currently in the clinic and lead to the development of better, more efficacious medicine for our patients.
Authorship: Veronica G. Anania (1), Qingling Li (1), Wyne P. Lee (2), Alessia Balestrini (2), Lorena Riol Blanco (2), Tracy L. Staton (1), W. Rodney Mathews (1)
(1) Department of Biomarker Development, (2) Department of Immunology, Genentech, Inc., South San Francisco, CA 94080, USA.
| Short Abstract Although it is recognized that mast cells are important in asthma, biomarkers to measure mast cell activity in clinical samples are lacking. Additionally, bioactive lipids produced by mast cells play an important role in airway inflammation, yet these lipids are not measured in clinical trials due to lack of robust assays. To address this issue, we developed a multiplexed mass spectrometry assay to quantify bioactive lipids in several biological sample types including bronchoalveolar lavage (BAL) fluid, nasal mucosal lining fluid, and urine. Based on this in vitro and in vivo data, urinary lipids have been included as exploratory biomarkers in several ongoing asthma clinical studies. In conclusion, our study indicates that bioactive lipids represent a novel class of clinical pharmacodynamic biomarkers that can be utilized to assess mast cell activity in the context of a clinical trial. |
Long Abstract
Asthma is a heterogeneous, chronic disorder of the lungs characterized by narrowing of the airways that results in bronchoconstriction, swelling and edema of the airway lining, and increased mucus production. Many of the clinical characteristics of asthma are initiated by mast cell activation which results in secretion of preformed and rapidly synthesized inflammatory mediators. These mediators include proteases, histamine, and inflammatory bioactive lipid molecules, some of which are targets of current asthma therapeutics and molecules in clinical development. Although it is recognized that mast cells are important for the early asthmatic response, biomarkers to measure mast cell activity in clinical samples are lacking. Moreover, it is well established that inflammatory bioactive lipids produced by mast cells (such as eicosanoids) play an important role in airway inflammation, yet these lipids are typically not measured in clinical trials due to lack of robust assays. To address this issue, we have developed a multiplexed mass spectrometry based method to quantify bioactive lipid molecules in biological samples including bronchoalveolar lavage (BAL) fluid, nasal mucosal lining fluid, and urine. Our method contains 19 isotopically labeled standards to perform absolute quantitation on >100 bioactive lipid metabolites in a single LC-MS/MS method. Using this approach we profiled the kinetics of eicosanoid production by mast cells in culture. Additionally, we were able to detect mast cell-produced eicosanoids in BAL fluid from a preclinical allergen challenge model. To assess utility of eicosanoids in samples that can be easily collected in the clinic, we measured urinary bioactive lipid metabolites in urine samples collected from moderate to severe asthmatics. Based on this data, urinary eicosanoids are being included as exploratory biomarkers in several ongoing asthma clinical studies. In conclusion, our study indicates that mast cell-produced eicosanoids represent a novel class of clinical pharmacodynamic biomarkers that can be utilized to assess mast cell activity in vivo in the context of a clinical trial.
References & Acknowledgements:
| Description | Y/N | Source |
| Grants | no | |
| Salary | yes | Genentech |
| Board Member | no | |
| Stock | yes | Roche |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | no |