The 15^th International Symposium on Proteomics in the Life Sciences

Ashok Dongre, Ph.D., Senior Director and Head of Proteomics, Bristol-Myers Squibb, Boston, MA, USA

Scaling Proteomics: Transforming Biopharmaceutical Discovery and Translational Research​

Proteomics has matured significantly over the past three decades and is now experiencing a renaissance, driven by advances in both reagent-based profiling and mass spectrometry (MS), the gold standard in the field. As LC-MS platforms have evolved, proteomics has reached a new level of productivity, though it still faces adoption barriers compared to genomics.

 

This presentation explores how recent breakthroughs in LC-MS technology, combined with enterprise-scale deep learning analytics, are delivering timely, actionable insights across the drug discovery and translational research continuum.

 

In early discovery, integrating high-throughput screening with proteomic profiling enables unbiased identification of compound hits, target modulation, and pathway engagement. When paired with high-content imaging and other -omics data, these approaches offer a systems-level view of pharmacology.

 

As programs advance, proteomics supports structure-activity relationship (SAR) studies and deepens understanding of mechanisms of action (MoA), enabling early detection of off-target effects and improving compound selection. Chemical proteomics, combined with chemical biology, also facilitates target deconvolution from phenotypic screens.

 

AI and machine learning further enhance this process by predicting compound success based on MoA relevance in preclinical and clinical datasets. In translational research, proteomics enables assessment of target engagement, pharmacodynamics, and safety markers in preclinical models, while clinical findings can be reverse-translated for validation.

 

Unbiased proteomics is now central to discovering pharmacodynamic biomarkers, stratifying patients, projecting human doses, and guiding early clinical trials. These capabilities are reshaping how therapies are developed and translated to the clinic.

 

To borrow from Winston Churchill, this may be “the end of the beginning” for proteomics. The future holds immense promise for innovation that drives breakthrough therapies and transforms patient care.

Judith Steen, Ph.D., Associate Professor of Neurology, Harvard Medical School, Director of the Neuroproteomics Laboratory, Kirby Center, Boston Children's Hospital, Boston, MA, USA

To FLEX or not to FLEX?

Neurodegenerative disorders, such as Alzheimer's Disease, Frontotemporal Degeneration, Parkinson's Disease, and Amyotrophic Lateral Sclerosis, share a common pathological signature: the aggregation of specific proteins, including tau, TDP-43, and alpha-synuclein. These proteopathies represent a critical juncture where normal proteins transform into pathological entities, associated with neuronal dysfunction and death. Despite decades of research, the precise molecular mechanisms governing this transformation remain elusive.

 

To address this fundamental gap, we developed the innovative FLEXI Platform based on mass spectrometry proteomics, which provides unprecedented sensitivity and specificity for characterizing disease-associated protein modifications. Our approaches comprehensively map and quantify post-translational modifications on pathological protein aggregates extracted from human patients and animal models across disease progression timelines. By analyzing these "molecular fingerprints" in large patient cohorts, we have revealed distinct modification patterns that define disease stages, patient subtypes, and predict clinical trajectories.

 

Our studies have uncovered the sequential accumulation of tau modifications during Alzheimer's pathogenesis and identified specific chemical alterations that enhance tau's propensity to aggregate and propagate between neurons. Importantly, these precise molecular characterizations distinguish pathological protein species from their healthy counterparts, enabling the development of highly selective therapeutic strategies that target disease-driving protein forms while preserving essential physiological functions.

 

This presentation will highlight how quantitative proteomics has transformed our understanding of proteopathies and demonstrate how these insights create new paradigms for early diagnosis and precision therapeutics in neurodegenerative diseases.