Mirjana Maletic-Savatic, MD, PhD
Department or Service
- Texas Medical Center
|University Of Belgrade||PhD||Doctor of Philosophy||1996|
|University Of Belgrade||medical school||Doctor of Medicine||1985|
The brain has a remarkable ability to generate new neurons in our center of learning and memory, throughout our lifespan. The rate of neurogenesis can be affected by many factors, from metabolism to physical and social activity. I focus on understanding the mechanisms of adult neurogenesis and the factors that affect it, using the tools of chemistry, genetics, computational and systems neurobiology, and neuroimaging. My ultimate goal is to develop regenerative therapies, i.e., to stimulate birth and survival of new neurons in a targeted and controlled manner to enable safe treatment of a variety of disorders that affect memory and mood.
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 the 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.
• Imaging metabolomics
Sierra A, Encinas JM, Maletic-Savatic M. "Adult human neurogenesis: from microscopy to magnetic resonance imaging.." Front Neurosci 2011;5:47. Pubmed PMID: 21519376.
Ma LH, Li Y, Djuric PM, Maletic-Savatic M. "Systems biology approach to imaging of neural stem cells.." Methods Mol. Biol. 2011;711:421-34. Pubmed PMID: 21279615.
Allen GI, Maletic-Savatic M. "Sparse non-negative generalized PCA with applications to metabolomics.." Bioinformatics 2011 November 1;27(21):3029-35. Pubmed PMID: 21930672.
Sierra A, Encinas JM, Deudero JJ, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, Tsirka SE, Maletic-Savatic M. "Microglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis.." Cell Stem Cell 2010 October 8;7(4):483-95. Pubmed PMID: 20887954.
Maletic-Savatic M, Vingara LK, Manganas LN, Li Y, Zhang S, Sierra A, Hazel R, Smith D, Wagshul ME, Henn F, Krupp L, Enikolopov G, Benveniste H, Djuric PM, Pelczer I. "Metabolomics of neural progenitor cells: a novel approach to biomarker discovery.." Cold Spring Harb. Symp. Quant. Biol.. 2008;73:389-401. Pubmed PMID: 19022759.
Manganas LN, Zhang X, Li Y, Hazel RD, Smith SD, Wagshul ME, Henn F, Benveniste H, Djuric PM, Enikolopov G, Maletic-Savatic M. "Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain.." Science 2007 November 9;318(5852):980-5. Pubmed PMID: 17991865.
Mignone JL, Roig-Lopez JL, Fedtsova N, Schones DE, Manganas LN, Maletic-Savatic M, Keyes WM, Mills AA, Gleiberman A, Zhang MQ, Enikolopov G. "Neural potential of a stem cell population in the hair follicle.." Cell Cycle 2007 September 1;6(17):2161-70. Pubmed PMID: 17873521.