The Roberts Lab utilizes advanced mass spectrometry technologies to find and quantify biological molecules as disease biomarkers. Our lab focuses on the understanding of the biological impact of protein modifications, changes in lipid metabolism, metal cofactors, and post-translational modifications. We are curious in the impact of these modifications on diagnosis and treatment of neurodegenerative diseases.
Our primary research includes: quantitative biological approaches to understand neurodegeneration, blood biomarkers for neurodegenerative diseases, development and application of metalloproteomics to neurodegenerative diseases, and translation of basic research to commercial and clinical use.
The Roberts Lab has used bioanalytical skills to answer important questions on Alzheimer’s disease such as how much neurotoxic peptide amyloid beta is in a diseased brain and how long it took to accumulate. We were able to determine that only Ca. 5 mg of amyloid beta separates a person with Alzheimer’s from a cognitively normal individual using a combination of molecular imaging with post-mortem analysis. With this, there is hard therapeutic targets for drug trials that indicate that a subtle increase of 5-10% in the clearance of amyloid beta would prevent the onset disease. The quantitative approach to Alzheimer’s disease characterized the di-tyrosine cross-linked version (a minimal toxic unit) of the amyloid beta peptide. While characterizing this target, we also devised a general method for searching for di-tyrosine cross-linked peptides.
With this research, ACS selected our publication as the Editors’ Choice. We have discovered that more than 80% of amyloid beta is isomerized in AD brains, which is a modification missed with traditional mass spectrometry and was only made possible with applying ion mobility MS to allow us to distinguish the isomers with changes in shape.
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Considerable work has been done on the discovery and validation of blood-based biomarkers within the Roberts Lab, including the role of metalloproteins transferrin and ceruloplasmin blood as markers for Alzheimer’s disease. We have also investigated the bulk levels of Fe, Cu, and Zn. This research demonstrates the experience of the lab in identifying and validating blood-based biomarkers. In addition to measuring and characterizing metalloproteins, our lab has also investigated plasma levels of amyloid beta as biomarkers for AD.
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Our lab over the past couple years has worked to develop and apply proteomic techniques that allow the direct measurement of the proteins and metal cofactors. This is important to understanding the role of essential metals (Fe, Cu, and Zn) and the proteins that use them for biological function. We established mass spectrometric and analytical tools to develop techniques to directly measure metalloproteins from biological samples, which includes imaging. Using metalloproteomics tools, the mechanism of action for CuATSM, the potential therapeutic for AMS, was uncovered. Due to this work, this compound is currently being evaluated as a treatment for ASL and Parkinson’s in clinical trials.
Several technologies identified in the Roberts Lab from our basic research are being pursued as commercial products. This includes the blood-based biomarkers for Alzheimer’s and Parkinson’s disease. Work is also being done to develop commercial products from metalloproteomics analysis. The metalloproteomic workflows have directly contributed to CuATSM translation to an ALS clinical trial and Parkinson’s disease.
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