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Neuregulins Play Pivotal Role in Development and Disease

 

Dr. Loeb studies neuregulin expression.

 

When Jeffrey Loeb, MD, PhD, began studying neuregulins, he was simply interested in synapse formation in the brain.  What he discovered, however, were the multiple roles they play in everything from cardiac growth to spinal cord development, to ovarian and breast cancer, and a variety of neurological disorders, including epilepsy and multiple sclerosis.

Dr. Loeb studies the molecular events that regulate the formation of synapses in the developing nervous system.  “A synapse is the central node of communication between nerves,” explains Dr. Loeb.  “By looking at the neuregulins and other regulatory molecules that facilitate this communication, we can learn about the interactions between pre- and post-synaptic cells that make a synapse function properly.  This basic scientific knowledge will provide us with a better understanding of both normal neurological processes and diseases of the nervous system.”

Thanks to his dual roles as researcher and physician, Dr. Loeb understands the clinical implications of his laboratory work.  Because of his interest in the molecular mechanisms of the brain, he noticed altered neuregulin (NRG) levels in his patients with neurological diseases including multiple sclerosis (MS).   In the case of MS, he has been awarded a grant from the National Multiple Sclerosis Society to study this.  “Clearly, this molecule is important in both development and in remodeling the nervous system,” Dr. Loeb said.  Dr. Loeb was also awarded a grant from the Children’s’ Research Center of Michigan to study NRGs in motor neuron development and diseases of motor neurons such as ALS.

As it turns out, NRGs also figure prominently and are highly expressed in heart and spinal cord development.  Last year, Dr. Loeb co-authored a study in Developmental Biology showing that NRGs play a crucial role in cell interactions during cardiac development.  Intense expression was observed in the endothelial lining of major blood vessels suggesting a role in the development of endocardial cushions and heart valves.  In fact, when the NRGs are altered, the heart valves fail to form.

 

This figure shows that neuregulin is highly expressed in the developing chick spinal cord (left) and the early hippocampus in the developing mouse brain (right).

 

Another study in Development traced the expression and distribution of NRGs during the formation of the spinal cord and neuromuscular synapses in embryonic chicks and mice.  Dr. Loeb and his colleagues found NRGs present all along motor and sensory axons from the moment they formed.  In addition, the presence of NRGs decreased later during development, suggesting transient roles in the developing synapses.  Dr. Loeb’s recent appointment to the Karmanos Cancer Institute will establish new collaborations to study the association between NRGs and several forms of cancer where NRG receptors are over-expressed.

Dr. Loeb is an assistant professor in neurology and the Center for Molecular Medicine and Genetics.  He earned his MD and PhD at the University of Chicago and completed his neurology residency at Massachusetts General Hospital.  He performed brain development research at Harvard Medical School and practiced at Harvard’s Beth Israel Hospital Comprehensive Epilepsy Center before joining WSU in 1998.

 

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