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Fred H. Gage

 

Fred H. Gage

Fred H. Gage

Professor and Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases
Laboratory of Genetics

"How the adult central nervous system adapts to environmental stimulation may hold the key to new therapies that replace or enhance damaged brain and spinal cord tissues. That's why our lab is so intent on pursuing the mechanisms behind this process."

Each generation has to carve out its own place, whether it's a young stag challenging the patriarch of the herd or a recent college graduate seeking a job. In time, the old invariably gives way to the young, and the cycle begins all over. Gage and his team discovered that a similar drama plays out in the brain, where newborn neurons ingratiate themselves into existing neuronal circuits and eventually edge the older nerve cells out.

Using high-tech imaging technology and electron tomography, they tracked the process behind the passing of the neurological baton. At the age of three to four weeks, newborn neurons send out tiny feelers that probe the environment in search of synapses already connected to other neurons. As the neurons mature, the feelers' tips fill out and start to monopolize the synaptic connections, elbowing the mature neurons out of the way. Their behavior suggests that, like herd animals in the wild, their fate may depend on their ability first to connect to an existing neural circuit and then to compete successfully with the older neurons.

Altering, not fulfilling, destiny lies behind another recent discovery in the Gage laboratory. While scientists have become adept at coaxing adult neural stem cells, the progenitors of all cell types in the brain, to change their lineage in a Petri dish, it had been thought that within the brain itself, their destiny was pretty much fixed. By introducing a single gene into neural stem cells in a mouse brain, however, Gage and his colleagues were able to induce those preordained to become neurons to switch teams, becoming glial, or support, cells instead. Specifically, they grew up into oligodendrocytes, specialized cells that form myelin, a fatty insulation layer that speeds up electrical signals traveling along axons.

While this finding has great significance for stem cell research in general, it is of particular interest to patients with multiple sclerosis. In that disease, the immune system attacks oligodendrocytes, thinning the myelin layer. By directing neural stem cells to differentiate into oligodendrocytes, scientists may someday be able to alleviate the symptoms of this perplexing and debilitating condition.

Lab Photo

Left to right:
Back row: Dane Clemenson, Nicole Coufal, Hoonkyo Suh, Tatjana Singer, Brian Feng, David Olivera, Stefan Aigner, Justin Arnold, Koji Shimozaki, Alysson Muotri Middle row: Beate Winner, Anthony Vu, Kristen Brennand, Wei Deng, Brad Aimone, Xinwei Cao, Kim McIntyre, Eunice Mejia, Jonathan Scolnick, Stephane enoud, Carol Marchetto, Bobbi Miller, Sherry Christenson, Ruth Keithly, Ahmet Denli Front row: Lara Rangel, Yangling Mu, Gene Yeo, Jaso Ray, Lisa Wolf, Grace Peng, Fred H. Gage, Lynne Moore, Yan Li, John Jepsen, Chunmei Zhao, Tiffany Liang

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Fred H. Gage

Fred H. Gage

Professor and Vi and John Adler Chair for Research on Age-Related Neurodegenerative Diseases
Laboratory of Genetics

Fred H. Gage, a professor in the Laboratory of Genetics, concentrates on the adult central nervous system and unexpected plasticity and adaptability to environmental stimulation that remains throughout the life of all mammals. His work may lead to methods of replacing or enhancing brain and spinal cord tissues lost or damaged due to Neurodegenerative disease or trauma.

Gage's lab showed that, contrary to accepted dogma, human beings are capable of growing new nerve cells throughout life. Small populations of immature nerve cells are found in the adult mammalian brain, a process called Neurogenesis. Gage is working to understand how these cells can be induced to become mature functioning nerve cells in the adult brain and spinal cord. They showed that environmental enrichment and physical exercise can enhance the growth of new brain cells and they are studying the underlying cellular and molecular mechanisms, that may be harnessed to repair the aged and damaged brain and spinal cord.

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