Brain Research Funded

UCLA brain research receives a boost from the Paul G. Allen Family Foundation
Tuesday, May 5, 2015

Research could one day aid the development of treatments for neurological diseases such as autism, Alzheimer’s disease, Parkinson’s disease, and others

Four researchers from UCLA have been selected for two of six awards recently announced by the Paul G. Allen Family Foundation. The awards will support work at the frontier of one of the most challenging roadblocks in neuroscience: growing mature human brain cells in the laboratory. The projects are funded at a total of $7.5 million over three years, with UCLA awards totaling $2.5 million. The new Allen Distinguished Investigators from UCLA are: Daniel Geschwind, Steve Horvath, William Lowry and Kathrin Plath. Geschwind, Lowry and Plath are also members of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

“This new cohort of Allen Distinguished Investigators and their research is especially significant because the field of neuronal maturation is at the leading edge of bioscience,” says Tom Skalak, Ph.D., Executive Director for Science and Technology for the Paul G. Allen Family Foundation. “The awardees’ broad talents and areas of expertise are what we need to explore this beckoning undiscovered territory.”

The Allen Foundation provides awards to leading investigators who are seeking innovations and world-changing breakthroughs. The four UCLA Allen Distinguished Investigators will explore ways to more efficiently and effectively create neurons, the core cellular components of the nervous system, which includes the brain, spinal cord and the nerves that reach throughout the body. Diseases of this system include autism, Alzheimer’s disease, Parkinson’s Disease, epilepsy and many other conditions.

Using mathematical models and an epigenetic clock to study neuronal maturation
Daniel Geschwind, M.D., Ph.D., and Steve Horvath, Ph.D., Sc.D., received an award totaling $1.2 million to create a better environment in which to grow mature neurons. One of the major obstacles to using human stem cells in the laboratory is that even the best systems yield immature or inconsistent cells. Geschwind, a professor of neurology and psychiatry and Horvath, a professor of human genetics and biostatistics, will use mathematical predictions to identify factors that drive neuronal maturation in the human brain but that are absent in neurons grown from stem cells in a petri dish cell culture. They will use these factors to create more stable cells that are similar to functioning neurons in the brain. These models can be used to identify therapies that could have potential benefits for patients by modifying the genetics of the cells or testing drugs on the cells while they’re in the petri dish, called ‘disease in a dish.’ Horvath has also identified an aging clock based on genetic measurements from thousands of cells and tissues; he and Geschwind will use similar methods to mimic the effects of aging in the laboratory.

Developing methods to improve the quality of neurons born in culture
William Lowry, Ph.D., and Kathrin Plath, Ph.D., received an award totaling $1.3 million to devise a model system to isolate and identify very specific types of neurons, which they can use to create neurons that are more like those found in the adult nervous system. Lowry, an associate professor of molecular, cell and developmental biology in the life sciences and Plath, a professor of biological chemistry, seek to overcome the obstacle of creating useful, pure pluripotent stem cells, since it is nearly impossible to create pure populations of particular subtypes of neurons or glia (the cells that protect neurons). Currently, neurons and glia generated in the lab are more similar to those found during early fetal development as opposed to the mature cells that are needed clinically. Their research, which focuses on particular types of neurons thought to be dysfunctional in various disorders including autism, Alzheimer’s disease and schizophrenia, could dramatically deepen fundamental biological understanding of the diseases and facilitate the eventual treatment of these devastating disorders.

“Driving basic scientific discovery to the clinic is a difficult and expensive process,” said Owen Witte, M.D., professor of microbiology, immunology and molecular genetics and director of the Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research. “We thank the Paul G. Allen Family Foundation for these awards and for their forward-thinking vision that is so critical to achieving our goal of developing therapies and cures for disease.”

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