Department of Chemistry & Biomolecular Sciences, Faculty of Science
University of Ottawa Heart Institute
University of Ottawa
Title: Forging sensitive tools to map inflammation by translational molecular imaging
Abstract: Inflammation underlies the earliest local tissue response to stress, contributing to the progression of a range of diseases and injuries including heart disease and concussion. At the biochemical level, inflammation occurs through a number of signalling pathways that result in innate immune activation and can lead to permanent alterations such as fibrosis or scarring. Our interest lies in the initiators of inflammation and the earliest biochemical markers predictive of inflammatory outcomes, and in the generation of imaging agents capable of mapping these markers with imaging modalities used in the clinic. This goal has guided our work generating imaging diagnostics for concussion by Magnetic Resonance Imaging (MRI), and for early heart disease by intravascular Optical Coherence Tomography (IV-OCT). During this seminar, our aldehyde-responsive contrast agent capable of mapping brain injury in a mouse model of concussion will be described, which provides a first-in-class objective imaging diagnostic of this prevalent injury. Our work developing a novel class of gold nanoassembly targeted to P-selectin will also be presented, opening up IV-OCT to molecular imaging and enabling personalized interventions not previously possible in cardiology. By targeting early initiators of inflammation, our novel chemical and nano-based imaging tools push the limits of our diagnostic capability with the goal of advancing our standard of medical care.
Bio: Adam became a Canada Research Chair in Chemical Biology and Assistant Professor at the University of Ottawa in 2015. He has received numerous accolades for his work, including the John Polanyi Prize in Chemistry from the Government of Ontario and the Young Investigator Award from the Radiopharmaceutical Sciences Council of the Society for Nuclear Medicine and Molecular Imaging. In 2023, he also received a Research Fellowship from the Killam Trust.
Adam and his research group continue to innovate and develop chemical tools to probe the chemical cues produced by cells at the earliest signs of disease or injury, with a broadened scope of practice beyond molecular imaging to encompass biomedical sensing. Their research focuses on problems ranging from imaging-based concussion diagnosis to developing home-based diagnostic tools for individuals. Adam also founded Ekidna Sensing, Inc., which produces rapid chemotyping tests for cannabinoid content analysis in the cannabis industry.
Aside from his research, Adam is also passionate about science communication and outreach efforts. He serves as the CEO of the Partnership Group for Science and Engineering, a position that allows him to advocate for the Canadian Science and Engineering communities to decision makers in the Canadian Government. Additionally, he is involved in the Indigenous Mentorship Program of Let’s Talk Science, which aims to create and deliver scientific activities to local and remote communities in Canada.
Université de Montréal
Title: Spinal cord remodeling across seven mouse mutant strains monitored by mass spectrometry imaging
Authors: *Rachel Pryce1, Hooman Bagheri2, Alan C. Peterson2 and Pierre Chaurand1
(1) Department of Chemistry, Université de Montréal, Montreal, Quebec, Canada
(2) Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
Abstract: Mass spectrometry imaging (MSI) is a powerful technique used to determine the localization of analytes in a sample. Matrix-assisted laser desorption ionization (MALDI) MSI is most often used to look at tissue sections where analytes of interest can be matched to specific histological regions. MALDI MSI is herein being used to look at a cohort of mice mutated in the enhancer region of myelin basic protein (MBP).
Myelin basic protein (MBP) is the basic structural protein of myelin and is responsible for connecting the lipid layers of the myelin sheath. Demyelination is involved in several neurodegenerative diseases, including multiple sclerosis. By researching the effects of demyelination in mouse models, it may be possible to glean further insight into these disorders.
Spinal cord MBP protein levels were measured using mass spectrometry imaging (MSI) to differentiate between the grey and white matter. Sections were first digested with trypsin before MALDI MSI analysis. A reporter peptide was used to measure relative MBP abundance. In 90-day-old mice, MBP levels were seen to vary from 120-5% of the wild-type abundance, showing a high correlation with mRNA levels.
As MBP is a major component of myelin, other changes in molecular composition across all mutants were suspected. Most notably, lipidomic variations were expected, especially for cholesterol, as it makes up 44% of the lipid component of myelin. From MSI measurements, cholesterol levels remained stable for the single-knockout mutants but decreased up to 30% in the triple-knockout mutant. Phospholipid abundance varied significantly across the cohort. For example, PC42:4 was observed 3.2-fold more abundant in wild-type mice with respect to the triple-knockout mutants, whereas PC40:1 and PC32:0 increased 4.4 and 3.0-fold, respectively, in the triple-knockout mutant with respect to wild-type mice.
The sum of these MSI results indicates major molecular remodeling of the myelin sheath with decreasing MBP levels.
Bio: Rachel Pryce is a second-year chemistry PhD student in the Department of Chemistry at the Université de Montréal. Her research is focused on the development of novel methods and protocols for mass spectrometry imaging of clinical and biological samples. Rachel completed her undergraduate studies in Biochemistry at the University of Waterloo.