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I was born in the countryside in China. We were very poor, so we had to be very self-sufficient. We grew our own crops and raised farm animals such as chickens and pigs for food. I think I naturally became interested in biology because I was exposed to animals and living things from such an early age.

When I was a master’s student in China, I came to Japan as an exchange student between universities. I enjoyed it so much that I applied for a scholarship from the Japanese government and came to Japan for my Ph.D. I later pursued post-doctoral work in the United States, but I missed my husband in Japan, so I returned here after my post-doc and joined Dr. Harada’s lab at TMIMS, since I enjoy working on visual systems and neurodegenerative diseases.

In 2010, we published a paper on the role of ASK1 in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. MS is an inflammatory autoimmune disease characterized by demyelination of neurons. EAE is a classic model for MS that is generated by injecting a myelin basic protein peptide into mice to generate an autoimmune response to myelin. Similar to MS, EAE induces demyelination of neurons, severe neuroinflammation, and neuronal death. We found that knocking out ASK1 decreases EAE symptoms, but we didn’t know exactly why this happened. We didn’t know the cell types where ASK1 was activated, and we didn’t know the pathway through which ASK1 affects the severity of EAE. ASK1 is also involved in other neurodegenerative diseases including glaucoma, amyotrophic lateral sclerosis, Alzheimer’s disease, and Parkinson’s disease, so understanding how ASK1 induces inflammation should be important for developing treatments for many diseases.

In our current paper, we worked to understand the cells and pathways that are activated by ASK1 to increase disease symptoms. Various types of immune cells are known to be involved in neuroinflammation, including T-cells, dendritic cells, microglia, macrophages, and astrocytes. We made conditional knockouts of ASK1 in each of these cell types to understand which cells need to express ASK1 to induce neuroinflammation. Altogether we found that ASK1 is needed in microglia early during EAE to start the inflammatory process, and then it’s later needed in astrocytes to maintain inflammation. To start inflammation, many proinflammatory cytokine/chemokine signaling genes need to be expressed, and ASK1 in microglia is needed for this to occur. Activation of microglia in turn, activates astrocytes which are needed to maintain inflammation. We found that this interaction between microglia and astrocytes also requires ASK1 in both microglia and astrocytes. Without ASK1 in both cell types, activation of astrocytes doesn’t occur. Altogether, we identified different cell interactions and molecular interactions through which ASK1 causes and maintains neuroinflammation. We hope to use this information to devise future strategies for treating neurodegenerative diseases.

We’re interested in developing novel treatments for glaucoma and MS. To do this, we’re pursuing three strategies. First, we’re collaborating with a pharmaceutical company to evaluate the effects of ASK1 inhibitor treatments on MS and other diseases. Second, we’re pursuing gene therapy approaches. In MS, myelin in oligodendrocytes is destroyed by autoimmune reactions. Using gene therapy, we plan to increase amounts of activated TrkB in oligodendrocytes to see if this induces remyelination. Third, we’re examining cell replacement strategies using stem cells. I just came back from Kobe Eye Center, where I learned how to make retinal ganglion cells from stem cells. We plan on making retinal ganglion cells and oligodendrocytes from stem cells to determine whether addition of these cells may reduce disease symptoms. MS is an extremely painful disease for both patients and their families. My hope is to contribute to the development of new, good therapies to help these patients.