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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 maintainance 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 varity of human diseases where
neurogenesis might be important.
Selected Publications
Maletic-Savatic M, Lenn NJ, Trimmer JS (1995) Differential spatiotemporal expression of K+ channel polypeptides in rat
hippocampal neurons developing in situ and in vitro. Journal of Neuroscience 15:3840-3851.
Maletic-Savatic M, Malinow R (1998) Calcium-evoked dendritic exocytosis in cultured hippocampal neurons. Part I: trans-Golgi
network-derived organelles undergo regulated exocytosis. Journal of Neuroscience 18:6803-6813.
Maletic-Savatic M, Koothan T, Malinow R (1998) Calcium-evoked dendritic exocytosis in cultured hippocampal neurons. Part II:
mediation by calcium/calmodulin-dependent protein kinase II. Journal of Neuroscience 18:6814-6821.
Maletic-Savatic M, Malinow R, Svoboda K (1999) Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic
activity. Science 283:1923-1927.
Mainen ZF, Maletic-Savatic M, Shi SH, Hayashi Y, Malinow R, Svoboda K (1999) Two-photon imaging in living brain slices.
Methods 18:231-239.
Nasr JT, Gabis L, Maletic-Savatic M, Andriola MR (2001) The electroencephalogram in children with developmental dysphasia. Epilepsy
and Behavior 2:115-118.
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.
Contact Information
- Mirjana Maletic-Savatic, M.D., Ph.D.
- Department of Pediatrics
- Section of Child Neurology
- Texas Children's Hospital
- Baylor College of Medicine
- One Baylor Plaza 919E - MS: BCM320
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-7340
- Fax: (713) 798-4744
- E-mail: maletics@bcm.edu
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