Meet a Whitehead Postdoc: Xin Tang

Xin Tang is a postdoc in Whitehead Institute Member Rudolf Jaenisch’s lab investigating brain disease and developing approaches to discover new therapies. We sat down with Tang to learn more about him and his experiences in and out of the lab.

What do you investigate?

My research interest is in brain disease, in getting a better mechanistic understanding of the brain and discovering drugs to help with treatment. The two main challenges that I see to treating brain diseases are, first, that we don’t know enough about the brain. We don’t know what the target genes are for which we can develop drugs. The second challenge is, once we’ve found those genes, we don’t have the therapeutic agents to target them efficiently to treat the disease. Since my PhD training, I have been using human stem cells to tackle these challenges. Stem cells are a great investigation tool because they can be derived from humans and can be differentiated into specific brain cell types, so they provide the right cellular signaling context to model brain disease. That helps to address the first challenge. However, my work at Whitehead Institute focuses on the second challenge, developing therapeutic agents, by using stem cells as a discovery tool to develop a robust high-throughput drug screening platform. With the platform, we can screen hundreds of drugs and find the ones that are able to regulate the expression of genes of interest in the types of cells relevant to the disease.

My recent work has focused on a gene called KCC2 that gets silenced in many brain diseases. We found the first group of drugs that can activate KCC2 gene expression in neurons and we tested the therapeutic efficacy of a variety of these drugs on models of a neurodevelopmental disorder called Rett syndrome. We saw amazing results in human cells and a mouse model, so now we're really eager to find out more about how these drugs work and how we could apply them to treat other brain diseases.

What is your scientific background and how did you end up at Whitehead Institute?

I got my undergraduate and master’s degrees in biomedical engineering, from Huazhong University of Science and Technology and Yale University, respectively. At the time, I wanted to use an engineering approach to study the brain, to essentially reverse engineer it, but then I realized that we don’t know enough about the brain for that to work. It is mostly a black box to us. I didn’t have much biology background at that time, so I decided my entry point into the brain, for my PhD, would be the interface between engineering and biology, and I chose to do electrophysiology. You can record electric signals from brain cells, and electric signals were something I knew very well. Then during my PhD, I started collaborating with a group that uses stem cells to model developmental dysfunction. I began to realize that stem cells held a lot of potential: virtually unlimited amount of human brain cells can be grown in culture dishes to model disease. I figured if I could edit the DNA source code of these cells, they would become even more powerful discovery tools. That's what drove me to apply to Rudolf's lab for my postdoc, he's a leading expert in this line of research. And I want to stay true to my physiologist background, so I have chosen a second advisor, a professor in the Picower Institute across the street, Mriganka Sur, and I have benefited tremendously from working with both of them.

What has been your experience interacting with patients affected by the brain disorders and diseases that you are working on?

The particular disorder that I have been studying is called Rett syndrome. It's a very severe type of neurodevelopmental disorder. We got funding support from a couple of Rett syndrome and autism research foundations, and throughout the last couple of years I’ve had the chance to go to their organized events to give talks, and I attend some of the local Rett syndrome patient events. When you meet the patients, the research work goes from being abstract to suddenly becoming very real. You feel the responsibility on your shoulders, and you get renewed energy to help those kids by doing solid and innovative science. You also get a sense of urgency because the kids you meet have suffered so much already—they are born with this genetic disorder—and there are always new kids being born with Rett syndrome, and there is no effective drug available for them. You feel the need to push for solutions not ten or twenty years from now, but as quickly as possible.

What is it like being in Rudolf’s lab?

Rudolf himself is a terrific mentor. He strikes a very good balance between giving people freedom to pursue what they want and giving them help when they need it—sometimes even when you don’t realize you need it. It's an art to balance those two. I also feel that he genuinely cares about the people in his lab. That's something I will carry to my own lab, giving my trainees both freedom and help, and really caring about their well-being and their success. 

In terms of my fellow researchers in the lab, what I find most interesting is that our lab has people from very diverse backgrounds, studying many different things, like diabetes, Zika virus, and various types of brain disorders. They are all top people in their respective fields. When I entered the lab, I was kind of humbled, because for my first month of lab meetings, half of the stuff I didn't understand. Now I've been in the lab for more than five years, and sat in enough lab meetings, that if, for example, I go to a meeting and talk to people who study diabetes or Zika virus, they would think I'm an insider of their field. You pick up so many different perspectives and understandings, and that has been so enriching.

Do you think that being in a lab with people investigating diverse topics has helped you when it comes to finding or engaging with collaborators?

I believe so. Inside Rudolf's lab, I learned many new research skills by working with other people in the lab. We have many past and ongoing collaborations. Also, since I have a second mentor across the street, and I go to their lab meetings every week, I get to experience that diversity as well. The labs have two different cultures and two different areas of expertise, and by experiencing both over the years I’ve become scientifically bilingual, so to speak. You start to look at the same question from different perspectives, and you become able to talk to different people using the language that's most efficient to communicate with them. It's a good skill to have. That’s even more true as a scientist working with clinicians. Learning to speak their language—it’s even more different, as is their culture. I’ve learned a lot through the process of talking with clinicians to understand their needs and convey my passion about the science I’m doing to them, and I look forward to more of those collaborations.

What are some of your hobbies?

I have a toddler daughter named Liyan at home, so most of my time is spent with her and my wife, Zaoli. Before we had a kid, I had two hobbies, gardening and crabbing. Gardening is almost like raising kids. You cannot control the environment, but rather you support your plants in that environment and you guide them as they grow on their own. You want to unleash their inner life energy, so you find ways to be a good supporter. That’s what I learned from gardening. Catching crabs, meanwhile, is almost like wrestling with nature. You need the right tool and the right experience, and there are no guarantees but if you are lucky you can get a big catch. For both of my hobbies, you get to eat what you harvest with friends and family at the end of the day, so that makes me very happy too.

When did you get into crabbing?

I started in Boston. I've always been a fishing guy. Growing up I did a lot of fishing. In Chongqing, China, we fished in the Yangtze river, in the ponds. Then at Penn State during my PhD we fished in a reservoir. When I came to Boston, I tried fishing in the sea but it's hard; it's a different game. Then I saw people catching crabs with just nets and I was fascinated, so I started doing that. 

What is one of your favorite non-work-related memories at Whitehead Institute?

A fond memory I have at Whitehead Institute is watching Rudolf and Rick Young [another Whitehead Institute Member]’s friendship. They not only write papers and grants together, but are also lifelong buddies. They travel the world together and tell stories about their journeys to us. Science can be a competitive profession, but if you can also connect with other scientists on a personal level and be yourself among your peers, then I think that’s great. That’s another lesson I’m taking away from working in Rudolf’s lab.

Where do you see yourself in ten years?

I am leaving Whitehead Institute to become a faculty member at Boston Children's Hospital starting in January 2021, where I plan to lead a group of really talented people who will strive to understand the basic mechanisms of brain disease and develop potential therapeutics. I really want us to push the boundaries of technology development because I think that innovative tools drive a lot of biology questions. Also, I will be in a clinical department, so I'll work closely with the clinicians to identify unmet medical needs, and then we’ll work together to develop appropriate technologies so that we can deliver feasible solutions that can help with diagnosis and treatment. I’d like to use my core strength in technology development, tailored to the specific needs of the clinic, to help improve patients' quality of life. If in ten years, we have advanced to somewhere near that goal, that would make me very, very happy.