Jane Zhu, M.D., Ph.D.
The bad news first: About 50% of children over the age of 18 months who are diagnosed with neuroblastoma already have metastases at the time of diagnosis. That means around half the children who learn they have this particular cancer also learn at the same time that it has already spread. Those children are at high risk of treatment failure and have a poor prognosis.
The good news: Your donations have helped fund innovative research on the mechanisms neuroblastoma cells use to spread. The results provide a crucial base for evaluating drugs that may prevent the metastases from occurring.
The even better news: The V-funded doctor leading the study has a sense of urgency matched only by the parents who hear that initial bad news. Fueled by that urgency, she has developed innovative tools to accelerate outcomes.
“I used to be a pediatrician. I always wanted to be a doctor. My dad was a surgeon, and he would come home and tell me the happy stories,” said Jane Zhu, M.D., Ph.D. “I can help patients, but I couldn’t help all of them. I watched some of them die, and that’s why I moved into the lab. People will be able to build on my work and find drugs to help these kids. So I decided to be a scientist and not just a physician,” she said.
For Zhu, gone are the days of lab rats and waiting weeks or months for answers. Following an instinct, and resolute in her determination to find answers, she used zebrafish as her model system in the lab.
“I always followed traditional guidance, but when I started my own lab, I had a gut feeling. My persistence paid off. I convinced them zebrafish were really good models,” she said.
The lure of zebrafish? They have no fur or hair, and you can see through them, making science happen in real time. They are most cost effective – 20 fit in one tank! One pair produces 200 babies. And, their anatomy has some similarities to human organs.
We have the ideal model system. We have huge amounts of sequencing data. We know which gene, when expressed at a higher rate, contributes to tumor growth. But the gene alone isn’t what is responsible for the tumor development. Zhu and her team suspected multiple genes were cooperating with each other to increase tumor growth and spreading. They engineered their fish to overexpress either the LMO1 gene or the MYCN gene and introduced highly visible, fluorescent proteins. They interbred the fish.
“We wanted to see: What causes the metastases? Are there interactions within the tumor cell? We saw the genes communicating,” Zhu said.
In her recently published paper, Zhu explains that in the offspring fish that expressed both genes, 60% developed multiple tumors.
We’re working as fast as we can. And the supporters are so generous. Without this support, we can’t do this. I just can’t appreciate it any more.
“This is the first evidence in an animal model that high levels of LMO1 expression promote metastasis of MYCN-induced neuroblastoma,” she said.
Zhu and her team have started to put together a significant part of the puzzle with their striking results. Their model helps scientists understand the mechanism of the disease. From here, the next step would be a collaboration with another lab that studies compounds. Their goal would be to test those compounds to see which has better tumor-stopping abilities. Remember – with transparent fish and the use of fluorescent proteins, those results will be seen in real time. Results could come faster than with other, more traditional models. Also, currently, there are no drug compounds to target the genes they found to be significant. Zhu’s team will look to see if other, already targetable genes can be looked at.
“We’re working as fast as we can. And the supporters are so generous. Without this support, we can’t do this. I just can’t appreciate it any more,” Zhu said.
As a V Scholar, Zhu presented cutting-edge ideas, and her lab pioneered a unique way to study neuroblastoma. The investment in her research has shown great promise for many children, in part because of a grant from the V Foundation that was made possible by support from people like you. Thank you for changing the course of pediatric cancer with us.