Email

mirjana.maletic-savatic@bcm.edu

Positions

Associate Professor

Pediatrics
Neurology
Baylor College of Medicine
Houston, Texas United States

Investigator

Jan and Dan Duncan Neurological Research Institute
Texas Children’s Hospital
Houston, Texas United States

Director

Human Disease Cellular Model Core
Intellectual and Developmental Disabilities Research Center
Baylor College of Medicine
Houston, Texas United States

Cynthia and Antony Petrello Endowed Scholar

Texas Children’s Hospital
Houston, Texas United States

Member

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States

Education

Clinical Fellowship at Stony Brook University

06/2002 - Stony Brook, NY United States

MD-PhD from University Of Belgrade

11/1996 - Belgrade, Serbia

Postdoctoral Training at Cold Spring Harbor Laboratory

06/1998 - Cold Spring Harbor, New York United States

Residency at Stony Brook University

06/1999 - Stony Brook, New York United States

Honors & Awards

Texas Academy of Medicine, Engineering, and Science (TAMEST) Protégé Award

Mark A. Wallace Endowment Scholar Award

Women in Medicine Award

Harris Medical Society and Health Museum Houston

Fellow of American Academy of Pediatrics (F.A.A.P.)

Neuroscience of Brain Disorders Award

McKnight Foundation

Best Doctors in America

Phillip R. Dodge Young Investigator Award

Child Neurology Society

Breakthrough Publication of the Year runner-up

Science journal (1999)

Professional Interests

• Adult hippocampal neurogenesis
• Brain repair and regeneration
• Lipids as signaling molecules and cell architects

Professional Statement

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.

Our research has uncovered an early critical period of newborn cell survival in the adult hippocampal neurogenic niche highlighting the role of microglia and neuroinflammation in neurogenesis (Cell Stem Cell 2010), a new communication pathway between the neural stem cells and their daughter cells (eLife 2017), and identified a novel fate of both neural stem cells (Cell Stem Cell 2015) and microglia (PloS Biology 2016) in the neurogenic niche exposed to chronic epilepsy. Our most recent work identified oleic acid as a long-sought endogenous agonist ligand of a nuclear receptor Tlx/Nr2e1, the master regulator of neural stem cell self-renewal and neurogenesis (PNAS 2022). Further, we are actively engaged in developing new methodologies for analysis of nuclear magnetic resonance spectroscopy (NMR/MRS) and mass spectrometry data (Bioinformatics 2011, Stat Anal Data Mining 2013), important for biomarker discovery in both biofuids and tissues in vitro and in vivo. To translate our discoveries to clinic, we also developed analytical algorithms to detect and quantify human hippocampal neurogenesis (Science 2007). Altogether, this work now gives us an opportunity to not only begin to systematically study human neurogenesis in vivo but also to target it specifically, toward new therapies aimed to increase the population of hippocampal stem cells and the production of newborn neurons.

Overall, our studies 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.

Websites

Selected Publications

• 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 Nov 9;318(5852):980-5. Pubmed PMID: 17991865
• 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 Oct 8;7(4):483-95. Pubmed PMID: 20887954
• 31. Sierra A, Martín-Suárez S, Valcárcel-Martín R, Pascual-Brazo J, Aelvoet S-A, Abiega O, Deudero JJP, Brewster AL, Bernales A, Anderson AE, Baekelandt V, Maletić-Savatić M*, Encinas JM* "Neuronal Hyperactivity Accelerates Depletion of Neural Stem Cells and Impairs Hippocampal Neurogenesis.." Cell Stem Cell. 2015;16(5):488-503. Pubmed PMID: 25957904
• 44. Semerci F, Choi WT, Bajic A, Thakkar A, Encinas JM, Depreux F, Segil N, Groves AK, Maletic-Savatic M. "Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance.." eLife. 2017;e24660. Pubmed PMID: 28699891