Rare Cell Studies Earn Researcher Prestigious Mass Spectrometry Award
by Matthew Pavlovich
Alexander R. Ivanov, research associate professor in the Barnett Institute of Chemical and Biological Analysis, has received a research award from the American Society for Mass Spectrometry. The award, one of only two given each year, provides a financial grant to young scientists to promote academic research in mass spectrometry. Professor Ivanov was presented with the award, sponsored by the Waters Corporation, in a plenary session of the 2015 ASMS annual conference in St. Louis, which more than 7,000 people attended.
Professor Ivanov’s research focuses on the advancement of mass spectrometry-based proteomic techniques for challenging biomedical applications. The main topics that Professor Ivanov is currently interested in include the development of ultra-low flow liquid phase separation techniques and interfacing them with advanced mass spectrometry for high-sensitivity proteomic profiling of biological samples and analysis of proteins and protein complexes in their native non-denatured states. Dr. Ivanov uses similar techniques for detailed characterization of isoforms and post-translational modifications of biologically active proteins, including biopharmaceuticals. Another rapidly emerging area that he studies using mass spectrometry-based proteomics is characterization of extracellular vesicles, including circulating exosomes and microparticles, as potential sources of biomarkers for disease diagnostics. Professor Ivanov has been also actively involved in national and international initiatives to develop standards for proteomic research.
The particular bioanalytical problem that Professor Ivanov proposed as part of the application process for the ASMS Research Award was the deep proteomic characterization of “rare cells,” which he describes as cells of limited availability that are difficult to obtain, including circulating tumor cells, stem cells and other progenitor cells. In the awarded proposal, Professor Ivanov designs new techniques to process and analyze limited populations of circulating rare cells and potentially individual single cells. The proposed research is largely based on his earlier results, published as the cover article in the June 2015 issue of the journal Molecular & Cellular Proteomics.
In this article, he takes a collaborative, multi-disciplinary approach to rare-cell proteomics, which starts by capturing and isolating individually selected cells using a microfluidic device developed by Shashi Murthy, a professor in the Department of Chemical Engineering, and his colleagues. A novel cell lysis process that Professor Ivanov developed then breaks apart the cells without using any chemicals, which enables accessing the cellular proteins with minimal losses. Finally, those proteins are characterized by advanced separation and mass spectrometry techniques in collaboration with the research group of Professor Barry Karger, director of the Barnett Institute. The paper describes the applications of the developed approach to the analysis of limited populations of cancer cells, hematopoietic stem cells, and endothelial progenitor cells in small volumes of whole blood.
Professor Ivanov hopes that the cover article, along with the ASMS research award, will further spur interest in the biomedical community and among funding agencies regarding the exciting new analytical approaches he has been developing and the interdisciplinary research that he and his colleagues at the Barnett Institute are conducting. The medical implications of this research include tracking disease progression by profiling small populations of tumor cells or individual brain neurons, which could enable personalized treatments for patients; characterizing the biology of cells in their microenvironments; and better understanding the differentiation of stem cells for developing new regenerative therapies.