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Stephen F. Heinemann

 

Stephen F. Heinemann

Stephen F. Heinemann

Professor
The Salk Institute Council Endowed Chair in Genetics
Molecular Neurobiology Laboratory

"The work in our laboratory is focused on the molecular mechanism by which nerve cells communicate with each other at specialized connections, or synapses. Recent work in the laboratory has supported the idea that many diseases of the brain result from deficits in communication between nerve cells or synapses."

Before senile plaques and neurofibrillary tangles, the hallmark of Alzheimer's disease, ravage the brains of its victims, the condition is marked by memory deficits and the loss of connections between brain cells. What this suggests is that communication between nerve cells is severely hampered long before the aggregate form of beta amyloid, which makes up the plaques, appears to interrupt the connections and ultimately cause neuronal death.

This finding prompted Heinemann to ask new questions about the disease: What if Alzheimer's disease is caused by defective synapses—the specialized communication interfaces between neurons—and dying brain cells are just the results of gummed-up connections? Using a mouse model engineered to overproduce a mutant form of the human amyloid precursor protein (APP) from which a number of smaller fragments, including the infamous beta amyloid, are cleaved off, Heinemann and his team studied the communication between nerve cells.

What they discovered is that the transmission of signals between brain cells in these mice is compromised long before neurons start to wither, and the interrupted cell-to-cell communication could explain the loss of memory that is apparent in earlier stages of the disease. On closer inspection, they discovered a possible culprit: a short, C-terminal APP fragment. When the formation of the fragment was blocked, the mouse was protected from the loss of synaptic transmission: Communication and memory were normal, and brain atrophy was eliminated, suggesting a new strategy to develop drugs to treat Alzheimer's disease.

In related work, Heinemann has examined the role of synapses in another common and debilitating condition: depression. He and his team studied patients diagnosed with major depression and linked the disorder to a specific brain receptor discovered in his laboratory. This receptor was shown to regulate the communication between nerve cells at the synapse—a discovery that may lead to new drugs to treat this widespread, perplexing malady.

Lab Photo

Left to right:
Standing: Ruadhan O'Flanagan, Corinne Teeter, Sunhwa Lee, Juan Pina-Crespo, Joe Snider, Mikio Suzuki, Conny Maron, Hosuk Lee, Jennifer Greenhall, Tresa McGranahan, Kacee Jones, Ed Han Seated: Jane Jenerette, Chuck Stevens, Steve Heinemann

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Stephen F. Heinemann

Faculty

Stephen F. Heinemann

Stephen F. Heinemann

Professor
The Salk Institute Council Endowed Chair in Genetics
Molecular Neurobiology Laboratory

Stephen F. Heinemann, a professor in the Molecular Neurobiology Laboratory, studies the molecular details of communication among brain cells. The synapse plays a key role in communicating information between brain cells and it is likely that biochemical changes at the synapse underlie some aspects of higher brain function. Most plausible theories of learning and memory depend upon changes in the efficiency of chemical synapses, which probably involves changes in receptors, ion channels and neurotransmitter release. It is also now known that these molecules can be directly involved in human disease. Most drugs that are used to treat mental illness are known to work either on the receptors or the metabolism of the transmitters at the synapse. The work in the laboratory is focused on the molecular biology and physiology of the glutamate and nicotinic receptors expressed in the brain. A major goal is to understand the regulation of synaptic function and the molecular biology of learning.

Among other notable achievements, his lab has isolated a gene containing the blueprints for a receptor critical to learning and memory, and identified the receptors that respond to nicotine. Since neurological ailments, such as Alzheimer's and Parkinson's; drug addiction; and mental disorders, such as depression and schizophrenia, are fundamentally disorders of brain cell communication, this research will provide new insights into the treatment of these disorders. Discoveries in Heinemann's lab are currently being used by pharmaceutical and biotechnology companies to develop drugs for stroke, epilepsy, Parkinson's and Alzheimer's diseases, as well as mental conditions, such as nicotine addiction, depression and schizophrenia.

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