Dhiman Ghosh (Sanofi)
Rapid, sensitive, reproducible, and accurate quantification of protein expression level in complex biological samples is critical to accelerate novel drug target identification and validation. Obtaining deeper proteome information can, therefore, help to gain insights into the biological complexities beyond noise and to connect cellular responses to pharmacological substance for drug mechanism of action (MOA) studies. In the past, comprehensive analysis of proteome has been attempted through limitless fractionation of digested proteins into less complex mixture of peptides that, however, provided little or no help in removing randomness from protein identification and quantification by label-free mass spectrometry. Additionally, extremely lower throughput in sample processing and data acquisition prevented even the analysis of a moderate size sample batches within a predicted time frame. On the contrary, singleshot label-independent DIA-MS (FAIMS/PASEF) platform can overcome many of the challenges associated with conventional proteomics. Applications of singleshot platform for global proteomics and phosphoproteomics along with target validation through FAIMS-PRM can be discussed.
Valesca Anschau (Biognosys)
Target identification is paramount in drug discovery as it ensures that a potential drug interacts specifically with its intended target in a biological system. Without proper target identification, a drug may not produce the desired therapeutic outcome or may have an off-target effect, leading to potential safety issues. Limited proteolysis (LiP-MS) emerges as a valuable tool in drug discovery pipelines for several reasons. It is an unbiased peptide-centric strategy that exploits 3D structural alterations and steric hindrance induced by drug binding to determine protein binding, estimate affinity (EC50), and predict binding sites from across the proteome. This provides a more realistic assessment of target engagement compared to traditional biochemical assays performed in vitro. This information is crucial for optimizing drug candidates to improve their efficacy and safety profiles. Also, LiP-MS can be used to identify potential off-target interactions of a drug candidate, which is important for predicting and mitigating potential side effects. To date, LiP-MS technology has been used extensively to characterize small molecules across species including data using a novel CDK9 inhibitor developed by AstraZeneca and a collaboration with Samsara Therapeutics, which enabled the efficient identification and validation of target proteins to understand biological systems in novel therapeutic development. By understating the full spectrum of protein interaction of a drug candidate, LiP-MS can provide valuable insights into target identification and help guide the development of novel therapeutics.
Short Bio Dhiman Ghosh:
Dhiman Ghosh is a Senior Principal Scientist and Lab Head in the Precision Medicine and Computational Biology (PMCB) division at Sanofi, in Cambridge, MA. With core expertise in mass spectrometry and proteomics, biomarkers, and bioanalysis he is spearheading a variety of efforts in exploratory research space requiring singleshot global and targeted proteomics platform development. Dr. Ghosh received his Ph.D. in Biochemistry and Medical Genetics from the University of Manitoba, Canada for his research work on the elucidation of membrane proteomes of lymphoid and myeloid precursors by mass spectrometry. During his postdoctoral work at the Institute for Systems Biology in Seattle, WA with Dr. Leroy Hood, he developed integrated multidimensional omics-based analytical platform to query disease-perturbed networks that revealed the identity of several blood circulating proteins with potentials in disease diagnosis. Dhiman held positions both in academia and industry and is passionate about the implementation of novel tools and technologies to advance the understanding of biology and drug discovery.
Short Bio Valesca Anschau:
Dr. Valesca Anschau is an Associate Scientific Director at Biognosys Inc. She holds a Ph.D. degree in Biochemistry from the University of Sao Paulo, Brazil, and completed her postdoctoral training in mass-spectrometry-based proteomics at the University of Valencia, Spain, SBP – Proteomics Department and Scripps Research in San Diego, California. With over a decade of experience working in several countries, Dr. Anschau has developed expertise in protein biochemistry, target-protein interactions, and mass-spectrometry-based proteomics. Her primary focus is to develop and optimize technologies for quantitative proteomics that can be applied in a drug discovery and development pipeline.
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