Assistant Professor, Baylor College of Medicine
M.D., University of Belgrade, Serbia, 1985
M. Sci., University of Belgrade, Serbia, 1988
Ph.D., University of Belgrade, Serbia, 1996
Postdoc, Cold Spring Harbor Laboratory, New York, 1999
Child Neurology Residency, Stony Brook University, New York, 2002
Imaging and metabolomics and neurogenesis
The long-term goals of my lab are to define and characterize the mechanisms that participate in the homeostasis of hippocampal neurogenesis and to develop imaging tools that would enable us to study neurogenesis in the live human brain. To achieve these goals, we utilize a variety of biochemical, molecular, imaging, and signal processing techniques.
We are specifically interested in mechanisms that increase the production and the survival of newly born neurons in the dentate gyrus. We study the role of electrical activity on the birth of new neurons, and the role of microglia, an innate immune cell in the brain, on their apoptotic death. We utilize transgenic mice in which neural stem/progenitor cells, neuroblasts, or microglia are labeled with fluorescent proteins, and we use a variety of primary culture and slice culture systems, confocal and multi-photon microscopy techniques, biochemical assays, and behavioral paradigms.
We also aim to translate our basic science research to clinical studies. To achieve this, we investigate the metabolic fingerprints of cells of interest, both in vitro (using NMR) and in vivo (using nMRI), and develop signal processing methodologies that enable detection of these fingerprints in the live human brain. Thus, we have developed a both cellular and systems metabolomics strategy that allows for identification and quantification of specific metabolites as well as sets of metabolites that are impaired in certain disease conditions. Once a specific fingerprint is determined and validated in cellular and animal models, we can apply it for human brain imaging, using MRI spectroscopy. We have already discovered a biomarker enriched in neural stem/progenitor cells, which enables detection of these cells in the human hippocampus. Using the same approach, we are now investigating the metabolic fingerprints of microglia.
Overall, our studies should provide critical insights into the basic principles involved in the maintenance of neurogenesis in both normal and abnormal conditions. In addition, our ability to image different cell types and metabolites in both animal models and the human brain using MRI techniques, enables us to readily translate our basic science knowledge to clinical studies of a variety of human diseases where neurogenesis might be important.
Manganas LN, Maletic-Savatic M (2005) Stem cell therapy for central nervous system demyelinating disease. Current Neurology and Neuroscience Report 5:225-231.
Mignone JL, Roig-Lopez JL, Fedtsova N, Schones DE, Manganas LN, Maletic-Savatic M, Keyes WM, Mills AA, Gleiberman A, Zhang MQ, Enikolopov G (2007) Neural potential of a stem cell population in the hair follicle. Cell Cycle 6:2161-2170.
Manganas LN, Zhang X, Li Y, Hazel RD, Smith SD, Wagshul ME, Henn F, Benveniste H, Djuric PM, Enikolopov G, Maletic-Savatic M (2007) Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318:980-985.
Maletic-Savatic M, Vingara LK, Manganas LM, Li Y, Zhang S, Sierra A, Hazel A, Smith D, Wagshul ME, Henn F, Krupp L, Enikolopov G, Benveniste H, Djuric PM, Pelczer I (2008) Metabolomics of neural progenitor cells: a novel approach to biomarker discovery. Cold Spring Harbor Symposia on Quantitative Biology 73:159-172.
Sierra A, Encinas JM, Deudero JJ, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, Tsirka SE, Maletic-Savatic M (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7:483-495.
Allen GI, Maletic-Savatic M (2011) Sparse non-negative generalized PCA with applications to metabolomics. Bioinformatics 27:3029-3035.
Ma LH, Li Y, Djuric PM, Maletic-Savatic M (2011) Systems biology approach to imaging of neural stem cells. Methods in Molecular Biology 711:421-434.
Sierra A, Encinas JM, Maletic-Savatic M (2011) Adult human neurogenesis: from microscopy to magnetic resonance imaging. Frontiers in Neuroscience 5:47.
Mirjana Maletic-Savatic, M.D., Ph.D.
Department of Pediatrics – Neurology
Baylor College of Medicine
1250 Moursund St. – NRI, Suite N1250.16
Houston, Texas 77030, U.S.A.
Tel: (832) 824-8807
Fax: (832) 825-1249