Dizon Laboratory
Mission Statement
My vision for the lab is one
of an industrious/good-natured/creative workspace for the biological problem of
perinatal hypoxia-ischemia-induced white matter injury, with the goal of
ultimately developing therapies for this important clinical problem. Members
should have goals for themselves regardless of whether their membership is
transient or more permanent in nature.
General Information
The brain of preterm babies
is particularly susceptible to white matter injury. Although the etiology of
preterm brain injury is multifactorial, hypoxia-ischemia dominates as a
mechanism. Oligodendroglial cells that are responsible for the production of
white matter are particularly susceptible to this mechanism of injury. The
clinical manifestation of white matter injury is cerebral palsy. Currently there
is no specific medical therapy to prevent cerebral palsy. Our goal is to better
understand how this cell lineage responds to hypoxia-ischemia, to identify
endogenous reparative responses by this cell lineage and to augment these
responses both in order to protect white matter from hypoxic-ischemic injury as
well as to regenerate lost white matter. Our approach is to combine a
well-accepted injury model with mouse transgenics. Our recent work focuses on
manipulation of the BMP signaling pathway as a potential therapeutic target.
Current Projects
Downregulation of Bone
Morphogenetic Signaling
Bone morphogenetic proteins
(BMPs) negatively regulate oligodendroglial fate choice by uncommitted neural
progenitors. Thus, we are currently investigating whether downregulation of BMP
signaling can protect and/or regenerate white matter in mice that have been
subjected to hypoxia-ischemia, by increasing commitment of progenitors to the
oligodendroglial fate and thus increasing white matter production. We use a variety
of transgenic mice in these experiments, including BMP antagonist
overexpressors, BMP receptor sub-type knock-outs, as well as BMP receptor
sub-type conditional inducible knock-outs.
Selected References
Dizon M, Maa T, Kessler JA.
(2011) The bone morphogenetic protein antagonist noggin protects white matter
after perinatal hypoxia-ischemia. Neurobiology of Disease 42:318-326.
Dizon M, Szele F, Kessler JA. (2010) Hypoxia-ischemia
induces an endogenous reparative response by local neural progenitors in the
postnatal mouse telencephalon. Developmental Neuroscience 32:173-183.
Ocbina PJ, Shin L, Dizon ML, Szele FG. (2006)
Doublecortin is necessary for the migration of adult subventricular zone cells
from neurospheres. Molecular and Cellular Neuroscience 33:126-135.
Dizon ML, Shin L,
Sundholm-Peters NL, Kang E, Szele FG. (2006) Subventricular zone cells remain
stable in vitro after brain injury. Neuroscience 142:717-725.
Dizon ML, Szele FG. (2005)
The subventricular zone responds dynamically to mechanical brain injuries. In:
Mammalian Subventricular Zones: Their Roles in Brain Development, Cell
Replacement and Disease. Levison SW, Editor. New York: Springer.
Romanko MJ, Radoslaw R, Fike
JR, Szele FG, Dizon ML, Felling RP, Van Guilder H, Brazel CY, Levison SW.
(2004) Roles of the mammalian subventricular zone in cell replacement after
brain injury. Progress in Neurobiology 74:77-99.
Dizon ML, Brown LA, Black
SM. (2004) Brain nitric oxide synthase levels increase in response to antenatal
ethanol exposure. Alcohol and
Alcoholism 39:101-105.
Wainwright MS, Brennan LA,
Dizon ML, Black SM. (2003) p21ras Activation following
hypoxia-ischemia in the newborn rat brain is dependent on nitric oxide synthase
activity but p21ras does not contribute to neurologic injury. Brain
Research 146:79-85.
People
Present
Maria Dizon, MD
Division of Neonatology,
Department of Pediatrics
Feinberg School of Medicine
Northwestern University
Prentice Women’s Hospital
250 E. Superior St. Suite
5-2144
Chicago, IL 60611
Tel (312) 472-4323
m-dizon@northwestern.edu
Derin Birch
Northwestern University
Department of Neurology
303 E. Chicago St.
Ward 10-233
Chicago, IL 60611
Tel (312) 503-2795
derinbirch2013@u.northwestern.edu
Past
Nikki Sundholm-Peters
Laura Shin
Jade Morris
Jill Toms