Millions of people are affected by brain disorders ranging from age-dependent neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s disease to psychiatric disorders such as Schizophrenia, depression, and autism spectrum disorders. Rapid advances in two areas of biology provide new hope to better understand these complex disorders. First, advances in human genetics and genome sequencing have greatly accelerated the discovery of genetic mutations that either cause or enhance the risk for these disorders. Second, new tools to study the brain have vastly expanded our knowledge of how the brain controls behavior. However, translating such knowledge into new therapies to cure these diseases has been very slow. To bridge this gap, we need a fundamental understanding of the molecular and cellular networks that normally regulate brain function, and a precise knowledge of the genes that may cause these diseases. Such transformative advances in neuroscience are dependent on seamless collaboration among investigators from multiple disciplines such as biology, computer science and engineering.
Mutant huntingtin, the causal disease protein in Huntington's disease, forms pathological protein aggregates in a mouse model of HD.
The Yang Lab showed two distinct brain regions, the cortex and striatum (labeled yellow and purple respectively), have distinct and synergistic contribution to pathogenesis of Huntington's disease.
A single medium spiny neuron in the mouse striatum labeled using genetically directed Mosaicism with Repeat Frameshift (MORF) cell labeling technology.
UCLA Neuroscientist X. William Yang, MD, PhD, merges human genetic findings and clinical observations from patients with cutting-edge genetic tools to study a variety of brain disorders, including Huntington’s, Parkinson’s, and Alzheimer’s diseases. His laboratory pioneered new genetic tools to develop models that mimic neurodegenerative disorders. He used these models to study disease mechanisms and test drug targets that could lead to future treatments for these devastating disorders.
His laboratory also studies a group of brain circuits called the basal ganglia that are involved in motor performance, motor skill learning, and reinforcement learning. Their innovative research on this circuitry provides new insights into the behavioral impairment seen in opiate addiction and Tourette Syndrome.
Finally, Dr. Yang’s team is collaborating with researchers around the globe to map out the detailed molecular networks that go awry in Huntington’s disease, and to develop an unbiased pipeline to identify potential targets for future treatments.
