scientist profiles

Holly Cline

Innovative Approaches to Developmental Neurological Disorders

For centuries, scientists and philosophers have wondered how the brain develops so that we can think, respond to events in our world and carry on a conversation. Most studies on brain development are indirect because it is difficult to make direct observations of the generation of new cells in the brain and the establishment of brain connections. Recent technological advances allow scientists to observe directly the growth of cells in the brain and how they respond to changes in the environment. These direct observations can give us key information on brain development, under healthy and disease conditions - Scripps Research Professor Holly Cline is taking advantage of these technological advances in pioneering ways.

Sensory experience is required for normal brain development. The goal of Holly's research is to determine the mechanisms by which sensory experience affects the development of brain structures and function. It involves studies that investigate which genes and proteins are required for enhanced neuronal activity, and could have relevance to a variety of developmental neurological disorders such as Fragile X Syndrome, Rett's Syndrome, autism spectrum disorders, and schizophrenia - which are the result of errors in the development of brain circuitry.

"Neuronal activity enhances development of the parts of the brain involved in that activity via a positive-feedback loop," Holly explains, "just as practicing a musical instrument enables musicians to perfect their performance."

"Sensory input can promote circuit development, so the brain is better equipped to process that information," she says. "This is a fundamental phenomenon in brain development, and also in brain plasticity - the way the brain changes in response to new experiences - and why sometimes it doesn't."

Holly came to Scripps Research from Cold Spring Harbor Laboratory where she was a Professor of Neuroscience for 14 years. She has brought 10 of her 14 international lab team members with her to Scripps Research! At Cold Spring Harbor, she made major contributions to the understanding of brain development and function.

She is particularly proud of her National Institutes of Health Director's Pioneer Award, which she received in 2005 to launch a large-scale project to understand the architecture, development, and plasticity of brain circuits. She was one of only 13 scientists to receive this annual award, which recognizes scientists who have far-ranging ideas that hold the potential to make truly extraordinary contributions to many fields of medical research.

The award supports the research of exceptionally creative scientists who take innovative approaches to major challenges in biomedical research. It is intended to give recipients the intellectual freedom to pursue groundbreaking new research with high potential impact that, due to their novelty, also have inherently high risks of failure. Holly received $2.5 million in direct costs for research, which she is still utilizing in her research here.

Holly's approach is indeed unique - it involves using in vivo imaging methods to watch the brain develop. "We're essentially taking movies of cells in the brains of living animals," she says. "We know that certain genes and proteins are important for brain development. We can increase or decrease the expression of these genes in our quest to find potential drug targets."

"One of the main reasons I came to Scripps Research is its fantastic reputation for taking gene and protein level experience to the next level of therapeutics," says Holly. She has been impressed in her time here. "We have an interactive and vibrant group of neuroscientists."

In one of her research projects at Cold Spring Harbor, Holly and her team demonstrated for the first time in living animals that insulin receptors in the brain can initiate signaling that regulates both the structure and function of neural circuits. The finding suggests a significant role for this class of receptors and perhaps for insulin, not only in brain development, but also in cognition and in pathological processes in which cognition is impaired, as in Alzheimer's disease, for example.

Holly received her Bachelor's degree from Bryn Mawr College, a small women's college, in 1977. After a few years as a technician at the Memorial Sloan-Kettering Cancer Center, Holly attended graduate school at the University of California, Berkeley, where she received her Ph.D. in 1985. Her thesis adviser, Gunther Stent, encouraged her interest in the plasticity of the visual system. She then went on to Yale University and Stanford University as a postdoctoral fellow, and later became an assistant professor at the University of Iowa.

Holly's daughter, Rose, is in her first semester at Georgia Tech University - she hopes to become an engineer.

"I'm driven by a basic curiosity," says Holly. "I am fascinated by events in brain development and want to understand them better."

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“One of the main reasons I came to Scripps Research is its fantastic reputation for taking gene and protein level experience to the next level of therapeutics," says Professor Hollis (“Holly”) Cline.