Mechanisms of neural stem cell self-renewal and differentiation in the brain and cancer
Neural stem cells are a group of cells that can reproduce themselves (self-renewal) and become other specialized neural cells such as neurons (differentiation). These two abilities of neural stem cells present the hope for replacing lost or damaged neural functions caused by disease or injury. In addition, genetic mutations in neural stem cells may be the cause of brain cancers. Therefore, one exciting outcome of neural stem cell study is the potential of finding treatments both for neurodegenerative diseases and nerve injury, as well as for brain cancers.
Two general strategies of neural stem cell therapy are being actively explored. One approach is to harness the potential of the existing neural stem cells in the brain to repair functional deficit. Another approach is to introduce neural stem cells cultured outside the body to replace lost or damaged function. For both approaches to work as we hope, we must learn more about how neural stem cells can be maintained in the stem cell state and how they can be guided to become a correct type of neurons to fulfill the specific function. A better knowledge of neural stem cell biology will help guide us to fully utilize the potential of neural stem cells (recovery of functions) but reduce the associated risk (tumor formation) in developing novel therapy.
The goal of our research is to better understand the biology of neural stem cells for the purpose of more effective use of their regenerative power. We have recently identified two cell signaling molecules, ephrin-B and Galpha, as critical players in regulating neural stem cell self-renewal and differentiation in the mouse brain. Specifically we have found that ephrin-B signaling is important for maintaining neural stem cells in the stem cell state, while Galpha signaling is important for promoting neural stem cells to become neurons. We propose to start from these two molecules to further identify the mechanisms controlling both normal and cancerous neural stem cells. A better knowledge of the mechanisms will provide more opportunities for developing stem cell therapeutics.
Neurodegenerative diseases and brain cancers affect tens of thousands of people in California, but there are no available cues or effective treatments. Neural stem cells carry the promise of providing treatments for neurodegenerative disease such as Parkinson's and Alzheimer's diseases, and they may also hold the key for understanding the cause of brain cancers. Our proposed study will bring benefit to people in California in several ways. First, our study on normal neural stem cells will yield important knowledge on how they are regulated by intrinsic and environmental factors. This knowledge will be useful for developing effective stem cell replacement therapy by providing insight on how to maintain and grow neural stem cells in culture and how to guide them to generate correct neuron types for a particular neurodegenerative disease. Second, our study on cancerous neural stem cells will lead to identification of novel drug targets and development of future treatments for brain cancers. Finally, a better knowledge of both normal and cancerous neural stem cells will be instrumental for developing a safe neural stem cell based replacement therapy.