Associate Professor (also with Neurology); Ph.D., 1987, M.D.,
1989, Chicago. Developmental neuroscience; molecular
mechanisms in synapse formation; neuroregulins and
neurotrophins in synaptic development; functional genomic
study of the pathogenesis of epilepsy.
Reasearch Interests
Our Laboratory has two main focuses. The
first is to understand the early molecular events regulating
the formation of synapses in the developing nervous system.
Our analysis centers on how soluble regulatory factors
such as the neuregulins and neurotrophins are modulated by
neuronal activity to orchestrate neuromuscular synapse
formation. Studies underway are examining how neuregulins
themselves are regulated during development through their
transcription, post‑translational processing and
association with the evolving extracellular matrix and the
functional consequences of this regulation on the expression
of acetylcholine receptors.
Much of what we have learned at the developing synapse
is relevant to interactions between neuronal axons and the
glia that surround them since the same signaling proteins are
used there as well. For
our studies, we use both the chicken embryo and transgenic
mouse models for in vivo studies that include electroporation
to modulate gene expression, as well as many in vitro studies
that includes real-time image analysis of living neurons in
culture. One of
our missions is to take the principles we have learned from
early development and apply these toward understanding and
treating diseases of the nervous system including multiple
sclerosis, where problems in axoglial communication are
present.
The
second major focus of the laboratory is to understand what
leads to the excessive neuronal activity in the human brain
that leads to seizures.
In this project we are examining human brain tissue
that is carefully mapped during epilepsy surgery in order to
determine what makes focal regions of human brain epileptic.
We are taking a functional genomic approach using
sophisticated microarray and bioinformatic technologies to map
gene expression patterns to the electrical abnormalities in
human epileptic tissues removed during epilepsy surgery.
We are identifying a common set of Aactivity-dependent@
human epilepsy genes that will develop new directions to
understand and treat this disease.
Selected Publications
Li Q, Loeb JA (2001) Neuregulin-HSPG interactions produce sustained ErbB receptor activation required for the induction of AChRs in muscle. J Biol. Chem. 276:38068-38075.
Loeb JA, Hmadcha A, Fischbach GD, Land SJ, and Zakarian VL (2002) Neuregulin Expression at Neuromuscular Synapses is Modulated by Synaptic Activity and Neurotrophic Factors , J. Neurosci. 22:2206-2214.
Loeb JA (2003) Neuregulin: An Activity-Dependent Synaptic Modulator at the Neuromuscular Junction. J Neurocytol. 32:649-664.
Li Q, Esper RM, and Loeb JA (2004) Synergistic Effects of Neuregulin and Agrin on Muscle Acetylcholine Receptor Expression. Mol. Cell. Neurosci. 26:558-69.
Esper RM and Loeb JA (2004) Rapid axoglial signaling mediated by neuregulin and neurotrophic factors. J. Neurosci. 24:6218-27.
Yao B, Rakhade SN, Li Q, Ahmed A, Krauss R, Draghici S, and Loeb JA (2004) Accuracy of cDNA microarray methods to detect small gene expression changes induced by neuregulin on breast epithelial cells BMC Bioinformatics 2004, 5:99
Li Q, Ahmed S, and Loeb JA (2004) Development of a proliferative autocrine neuregulin signaling loop during the malignant transformation of human breast epithelial cells . Cancer Research 64:7078-85
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