Parkinson’s Disease

Parkinson’s disease (PD), a severely debilitating adult-onset neurodegenerative condition, is characterized by a substantial depletion of a subset of midbrain dopamine neurons (mDA). This loss of mDA accounts for most motor deficits observed in this disease. Recent studies have revealed that specific subsets of mDA are lost in PD. This selective mDA neuron susceptibility in PD highlights heterogeneity of the mDA system. Thus, replacing specific subtypes of mDA, as opposed to generic mDA, has been highlighted as an important goal of stem cell based therapies for PD 15.
Our goal is to understand how different mDA subtypes are generated. Here, we propose experiments to define how in the embryo, midbrain progenitor cells are directed by specific gene/gene combinations to yield distinct mDA subtypes. To do so, we will indelibly label specific progenitor cell populations using conditional genetic techniques we and others have developed, and determine what subtypes of mDA are produced from distinct progenitor pools. These experiments will define the developmental basis for mDA diversity. Understanding the developmental cascades underlying mDA diversity will be critical for generating stem cell derived therapies or models of PD.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…