Blaine Roberts, PhD
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Associate Professor, Department of Biochemistry, School of Medicine
Scientific Director, Molecular Interactions, Emory Glycomics and Molecular Interactions Core, School of Medicine
Graduate Programs
- Full Member - Biochemistry, Cell and Developmental Biology
- Full Member - Neuroscience
Education
PhD, Oregon State University, 2007BS, Montana State University, 2002
Contact Information
Email: blaine.roberts@emory.edu
Phone: 404-727-6007
Address:
O. Wayne Rollins Research Center, Room G223
1510 Clifton Road NE
Atlanta, GA 30322
Nearly everything we study in biology and disease is the product of protein function. Whether it is normal enzymatic function or aberrant functions, proteins have a central role in the manifestation of the pathologies and phenotypes. The goal of my research program is to apply cutting-edge analytical technology and mass spectrometry to assist in the early diagnosis and treatment of neurodegenerative diseases. Specifically, we work to understand the mechanism of action for the toxic effects of neurological proteins (e.g. Amyloid-beta, alpha-synuclein, Cu, Zn-superoxide dismutase) and to translate this information into clinical outcomes. To do this we have developed and applied advanced analytical mass spectrometry tools to discover and measure metalloproteins (metalloproteomics). We have applied these tools to amyotrophic lateral sclerosis, and this has contributed to a first-in-class clinical trial for ALS and Parkinson's disease (NCT02870634 & NCT03204929). Our ongoing research aims to investigate; (1) the role of metalloproteins in biology (2) how post-translation modifications of proteins (e.g. dityrosine, nitrotyrosine, metal cofactors) contribute to protein function (3) the natural history of Ab and APOE in Alzheimer's disease (4) blood-based diagnostics for neurodegenerative diseases. As detailed below a major focus in my lab is to utilize the advanced mass spectrometry technologies to discover, validate and qualify biological molecules (e.g. proteins, metals) as disease biomarkers.
Our Alzheimer research aims to answer some basic questions about the role of amyloid beta in the disease. Our work, and others, demonstrate that the neurotoxic peptide amyloid beta accumulates in the brain for 20 years before someone develops clinical symptoms. We have shown that the reason for the accumulation of the peptide is due to a reduction in the clearance of the peptide from the brain. We reasoned that a post translational modification of the peptide could be the reason for amyloid accumulation. To investigate this, we applied ion mobility mass spectrometry to compare the amyloid beta peptides in AD brain to controls. Ion mobility mass spectrometry measures the shape of a molecule in addition to the standard mass spectrometry information (e.g. m/z, peptide sequence). We discovered that over 60% of the amyloid beta peptide in AD brain was isomerized making it the predominate form of the peptide in AD brain. The isomerization of amyloid beta reults in a peptide with a different shape and handedness this has implications for ability of proteases to clear the peptide and for antibody therapies that target amyloid beta to recognize the peptide. Currently, we aim to determine the biochemical consequences of isomerization in AD brain.
Neurodegenerative disease has a long history that implicates a role of copper, iron and zinc in the pathophysiology of Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. However, most of the investigations have relied on measurement of the total amount of metal in disease tissue vs control tissues. Although informative, it does not yield mechanistic detail on the pathways or proteins that directly use the metals as cofactors. We have developed proteomic techniques that allow the direct measurement of the proteins and metal cofactor. These techniques are being used to unlock the mechanistic link between changes in bulk levels of trace elements (e.g. Fe, Cu, Zn) to specific proteins and metabolic pathways. We are one of the few laboratories in the world dedicated to the measurement and characterization of metalloproteins in neurodegenerative disease. In particular we are excited to understand the role of metalloproteins in biology and disease.
The results from are investigations in metalloproteins and mechanism of neurotoxic proteins in neurodegeneration are often useful for detection and diagnosis of disease. We use a range of bioanalytical techniques from the next generation ELISA systems (e.g. Quanterix SIMOA) and quantitative mass spectrometry to translate our findings into clinically relevant biomarkers. Our goal is to improve the outcomes for those suffering from neurodegenerative diseases.
Two recent publications selected from 55 peer reviewed articles published since 2015:
1. McAllum, E.J., Hare, D.J., Voltakis, I., McLean, C.A., Finkelstein, D.I., Roberts, B.R. Regional iron distribution and ferroprotein profiles in healthy human brain. Progress in Neurobiology (2020) Mar;186:101744
2. Mukherjee, S., Fang, M., Kok, W.M., Kapp, E.A., Thombare, V., Huguet, R., Hutton, C.A., Reid, G., Roberts, B.R. Establishing Signature Fragments for Identification and Sequencing of Dityrosine Cross-linked Peptides using Ultraviolet Photodissociation Mass Spectrometry. Analytical Chemistry (2019) 91, 19, 12129-12133
Our Alzheimer research aims to answer some basic questions about the role of amyloid beta in the disease. Our work, and others, demonstrate that the neurotoxic peptide amyloid beta accumulates in the brain for 20 years before someone develops clinical symptoms. We have shown that the reason for the accumulation of the peptide is due to a reduction in the clearance of the peptide from the brain. We reasoned that a post translational modification of the peptide could be the reason for amyloid accumulation. To investigate this, we applied ion mobility mass spectrometry to compare the amyloid beta peptides in AD brain to controls. Ion mobility mass spectrometry measures the shape of a molecule in addition to the standard mass spectrometry information (e.g. m/z, peptide sequence). We discovered that over 60% of the amyloid beta peptide in AD brain was isomerized making it the predominate form of the peptide in AD brain. The isomerization of amyloid beta reults in a peptide with a different shape and handedness this has implications for ability of proteases to clear the peptide and for antibody therapies that target amyloid beta to recognize the peptide. Currently, we aim to determine the biochemical consequences of isomerization in AD brain.
Neurodegenerative disease has a long history that implicates a role of copper, iron and zinc in the pathophysiology of Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. However, most of the investigations have relied on measurement of the total amount of metal in disease tissue vs control tissues. Although informative, it does not yield mechanistic detail on the pathways or proteins that directly use the metals as cofactors. We have developed proteomic techniques that allow the direct measurement of the proteins and metal cofactor. These techniques are being used to unlock the mechanistic link between changes in bulk levels of trace elements (e.g. Fe, Cu, Zn) to specific proteins and metabolic pathways. We are one of the few laboratories in the world dedicated to the measurement and characterization of metalloproteins in neurodegenerative disease. In particular we are excited to understand the role of metalloproteins in biology and disease.
The results from are investigations in metalloproteins and mechanism of neurotoxic proteins in neurodegeneration are often useful for detection and diagnosis of disease. We use a range of bioanalytical techniques from the next generation ELISA systems (e.g. Quanterix SIMOA) and quantitative mass spectrometry to translate our findings into clinically relevant biomarkers. Our goal is to improve the outcomes for those suffering from neurodegenerative diseases.
Two recent publications selected from 55 peer reviewed articles published since 2015:
1. McAllum, E.J., Hare, D.J., Voltakis, I., McLean, C.A., Finkelstein, D.I., Roberts, B.R. Regional iron distribution and ferroprotein profiles in healthy human brain. Progress in Neurobiology (2020) Mar;186:101744
2. Mukherjee, S., Fang, M., Kok, W.M., Kapp, E.A., Thombare, V., Huguet, R., Hutton, C.A., Reid, G., Roberts, B.R. Establishing Signature Fragments for Identification and Sequencing of Dityrosine Cross-linked Peptides using Ultraviolet Photodissociation Mass Spectrometry. Analytical Chemistry (2019) 91, 19, 12129-12133
Diversity: Inclusion in the Modern Workplace, 2021
Lester Manly (he/him)
Molecular and Systems Pharmacology
Entrance Year: 2021
Topic: Utilization of mass spectrometry to investigate the pathophysiology of ALS.
