MRC Developmental Neurobiology Unit, London, UK, Laboratory of Dr. Robert Balazs
Laboratory of Preclinical Pharmacology, NIMH, NIH, Laboratory of Dr. Erminio Costa,
Department of Pharmacology, University College London, London, UK, Laboratory of Dr. Stuart Cull-Candy
Laboratory of Developmental Neurobiology, NICHD, NIH, Laboratory of Dr. Andres Buonanno, Bethesda, MD
Vittorio Gallo, PhD, is an internationally recognized neuroscientist and developmental neurobiologist. He is director of the Center for Neuroscience Research at Children’s National Medical Center in Washington, DC, and the associate director of the Mental Retardation and Developmental Disabilities Research Center at Children’s National. He holds an Endowed Chair, the Wolf-Pack Chair in Neuroscience, and is professor of Pediatrics and Pharmacology at the George Washington University School of Medicine. Dr. Gallo joined the staff of Children’s National Medical Center in 2002. He came from the NIH, where he was chief of the Section on Molecular and Cellular Neurobiology at the National Institute of Child Health and Human Development. He obtained his PhD in Biochemistry and Neurobiology from the University of Rome, Italy, where he worked with Prof. Giulio Levi and with the Nobel Laureate Prof. Rita Levi-Montalcini. Dr. Gallo was then a Fellow of the European Molecular Biology Organization (EMBO) in London, UK, where he first worked at the Developmental Neurobiology Unit of the Medical Research Council, studying neuronal differentiation in the cerebellum. He then continued his postdoctoral training at the Department of Pharmacology, University College, where he demonstrated the existence of glutamate-gated ionic channels in glial cells. Dr. Gallo came to the United States as a NATO Fellow to work at the NICHD, NIH, on the molecular biology of glutamate receptors. In 1996, he became a tenured investigator and chief of the Section on Molecular and Cellular Neurobiology. Research in Dr. Gallo’s center focuses on brain development and developmental disabilities. Dr. Gallo’s research team works on the early postnatal development of the three major types of cells of the central nervous system, neurons, oligodendrocytes, and astrocytes. His laboratory is interested in: neurogenesis in the postnatal brain, and strategies of cell repair and regeneration based on the use of postnatal neural progenitors; intrinsic and extrinsic signals that regulate oligodendrocyte progenitor proliferation, migration and differentiation, and the process of myelination; astrocyte signaling, and extracellular factors that regulate astrocyte proliferation in the normal and injured brain.
EMBO Fellow (1979)
EMBO Fellow (1981)
ETP (European Training Program in Brain Research) Study Award (1981)
International Society for Neurochemistry Travel Award (1983)
Italian Society for Neuroscience Young Investigator Award (1985)
EMBO Fellow (1988)
EMBO Study and Travel Award (1989)
NATO Fellow (1990)
Adan Aguirre, PhD (senior postdoctoral fellow)
Ying Cheng, MSc (research assistant)
Li-Jin Chew, PhD (research assistant professor)
Ainoha Echeverria, PhD (postdoctoral fellow)
Ana Gadea, PhD (postdoctoral fellow)
Robert Gueth, BSc, MSc (graduate student)
Beata Jablonska, PhD (postdoctoral fellow)
Jean Marie Mangin, PhD (postdoctoral fellow)
Xiaotian Ming, PhD (postdoctoral fellow)
Masae Naruse, PhD (postdoctoral fellow)
Matthew Raymond, BSc (graduate student)
Joey Scafidi, MD (clinical research fellow)
Thomas Schmitz, MD (visiting scientist, clinical research fellow)
Weiping Shen, PhD (postdoctoral fellow)
Dr. Gallo’s current and future research interests are in the fields of developmental neuroscience and in nervous system disease. They include: i) neurogenesis and gliogenesis; ii) oligodendrocyte development and myelination; iii) glial signaling; and iv) regulation of glial ionic channels during brain development. Dr. Gallo’s laboratory uses an integrated, multidisciplinary approach that includes molecular biology and genetics, cellular neurobiology and electrophysiology. They are combining experiments performed in different types of neural cell cultures with studies performed in transgenic mice in vivo.
Neurogenesis and gliogenesis: NG2-expressing progenitors are stem cells in the postnatal and adult brain. Dr. Gallo’s team is currently studying the NG2-expressing progenitor cells in perinatal and adult brain. These cells represent the largest population of postnatal progenitors in the brain. They are characterizing these cells in the postnatal and adult subventricular zone (SVZ), and analyzing the cellular and physiological properties of NG2+ cells in white and gray matter regions. Gallo is particularly interested in the developmental relationship between NG2+ cells and other cell types previously characterized in the SVZ. He will also continue to explore the type of neural progeny generated by NG2+ cells in the perinatal and adult brain using stem cell culture assays and by grafting NG2+ cells in vivo. Gallo’s data indicates that NG2+ cells display stem cell properties and generate GABAergic interneurons in the hippocampus, but can also give rise to oligodendrocytes in white matter and cerebral cortex. Future experiments will define whether intrinsic or extrinsic cues are responsible for distinct NG2+ cell differentiation pathways. For example, do differences between the white matter vs. gray matter environment contribute to lineage determination of these progenitors? Dr. Gallo will also continue to use transplantation techniques to determine whether NG2+ progenitors can be used for cell repair and regeneration purposes in epilepsy mouse models.
Oligodendrocyte development and myelination: Physiology and pathology. Gallo and his team are studying the effects of ETs on OPC development. They have found that ET-1 does not affect OPC proliferation but strongly promotes OPC migration and prevents differentiation to mature myelinating oligodendrocytes. They are currently analyzing ET-receptor B knock-out mutants to determine which ET receptor subtype is involved in the biological effects observed. We are also using two-photon live imaging in CNP-GFP tissue sections to study OPC migration and the effects of ET-1 in situ. The identification of a novel regulator of OPC migration will open new perspectives to the possibility of promoting migration of these progenitors in models of demyelinating diseases. Gallo is also studying the effects of interferon gamma (IFN?) on OPCs. The presence of activated T-cells around demyelinating lesions suggests the influence of inflammatory cytokines on demyelination and remyelination. IFN? is known to downregulate the expression of myelin genes in OPCs, but the molecular mechanism(s) underlying this phenomenon remains to be elucidated. Gallo’s team has observed that IFN? blocked the downregulation of cell proliferation that normally precedes terminal oligodendrocyte differentiation. IFN? increased OPC proliferation and attenuated myelin basic protein expression. Finally, IFN? significantly downregulated expression of transcription factors involved in OPC differentiation. These studies suggest that IFN? may contribute to the failure of remyelination by directly interfering with the physiological regulation of intracellular factors involved in OPC proliferation and differentiation.
Glial signaling: Endothelins and their receptors in astrocytes. Differently from OPCs, in astrocytes ET-1 promotes cell proliferation. We are currently determining the molecular mechanism, at the cell cycle level, that mediates the effect of ET-1. Dr. Gallo is also defining the relationship between activation of the c-jun pathway and regulation of astrocyte proliferation by ET-1. Finally, he is using microarrays to investigate genes that are regulated by ET-receptor activation in astrocytes. It is known that both ET-1 synthesis and ET-receptor levels are significantly upregulated in “reactive” astrocytes after lesion, therefore these studies will be important to define the role of ETs in astrocyte pathophysiology.
Regulation of ionic channels during development: Voltage-activated K+ channels and glutamate-activated channels in glia. My group is conducting in vivo and in vitro transgenic studies to further characterize glial receptors and channels. Dr. Gallo is analyzing the consequence of manipulating receptor and channel function on oligodendrocyte development and physiology by using a molecular, cellular and physiological approach. Dr. Gallo’s lab team is currently overexpressing different Shaker K+ channel subunits in OPCs in culture and in vivo, to determine their role in oligodendrocyte development. They are particularly interested in KV1.3, since they have previously demonstrated that blocking outward K+ channels with KV1.3-specific blockers affects OPC development. Dr. Gallo has also generated transgenic mouse lines in which the glutamate receptor subunit GluR1 is selectively silenced in OPCs by a loss-of-function mutation. Future studies will define the consequence of this loss-of-function on OPC development in vivo and in vitro.