Nathalie Agar, Ph.D.
Director, Surgical Molecular Imaging Laboratory, Department of Neurosurgery, Brigham and Women’s Hospital
“Mass Spectrometry for Surgical Pathology and Drug Development”
Mass spectrometry provides a new tool for the direct profiling of tissue during neurosurgery, and can also provide significant insight in the development of drugs targeting tumors of the central nervous system.
Using desorption electrospray ionization mass spectrometry (DESI MS), we rapidly detect tumor metabolites from surgical tissue without complex or time-consuming preparation. The method was validated by correlating 2D mass spectrometry imaging of brain tumor specimens with histopathology, and used to detect tumor tissue within seconds to minutes. Imaging tissue sections with DESI MS shows that diagnostic molecular signatures overlap with areas of tumor, thereby indicating tumor margins. We have installed a mass spectrometer in our Advanced Multimodality Image Guided Operating (AMIGO) suite at Brigham and Women’s Hospital and demonstrate the molecular analysis of surgical tissue during brain and more recently breast cancer surgery.
Drug transit through the blood-brain barrier (BBB) is essential for therapeutic responses in brain tumors. Using matrix assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) in pre-clinical animal models and clinical trial samples, we visualize drug and metabolites penetration in brain tissue without molecular labeling. We validated heme as a simple and robust MALDI MSI marker of the vasculature and go on to provide examples of how MALDI MSI can provide chemical and biological insights into BBB penetrance and metabolism of small molecule inhibitors in the brain.
Ph.D. Chemistry (Dr. Justin Powlowski), Concordia University, Montreal, Canada, 2002
B.Sc. Biochemistry, Laval University, Quebec, Canada, 1997
Postdoctoral Fellow, Neurosurgery (Dr. Rolando Del Maestro), McGill University, Montreal, Canada, 2002-2005
Postdoctoral Fellow, Neurosurgery (Dr. Peter M. Black), Harvard Medical School, 2005-2007
Honors and Prizes:
Inorganic Biochemistry Summer Workshop (IBSW), Center for metalloenzymes studies (CMS), University of Georgia, Selected participant, 1998
Workshop on the Biosynthesis of Iron-Sulfur Clusters, Virginia Tech, Invited participant, Documented in Chemical and Engineering News from the American Chemical Society (Nov. 2001), 2000
First Course on Molecular Mechanisms in Brain Tumors, M.D. Anderson Cancer Center and the American Brain Tumor Association, Selected participant, , 2003
Brigham Leadership Program, Brigham and Women’s Hospital and Harvard Business School, Executive Education in Leadership, 2008-2009
Inducted to the Society of J.W. McConnell Awardees, J.W. McConnell Foundation, 2009-present
NIH Director’s New Innovator Award, National Institute of Health, National Institute of General Medical Sciences, 2010
2011 BWH Palmie Award, Brigham and Women’s Hospital, Recognition for innovative research and funding accomplishment
Date(s) - March 9, 2015
Emplacement / Location
Morris and Rosalind Goodman Agora