Faculty Spotlight: Brian Chadwick

Brian Chadwick is an associate professor of biology in the Department of Biological Sciences, part of Florida State University’s College of Arts and Sciences. He earned his doctorate from University College London in 1997. Since then, he has conducted research on gene expression, specifically X chromosome inactivation, and how that can translate to gene silencing on all chromosomes.

Tell me about your background.

I was born and raised in Sutton, a small village located in the Norfolk countryside on the east coast of England. My high school was quite small with around 100 students per grade level. We specialize early in the U.K., so, when I attended sixth form college, I only studied three subjects: biology, chemistry and geography. As a country boy, I was a little afraid of big cities. I faced that fear by moving to London to pursue my bachelor’s at Imperial College and stayed in London for my Ph.D. at the Imperial Cancer Research Fund, or ICRF, now called Cancer Research U.K., and was affiliated with University College London.

When did you first become interested in biology?

I’ve always been interested in biology. Living in the countryside, I was surrounded by nature and loved to go pond dipping, look for crabs on the beach, watch birds, or walk through the woods. My real interest in biology took hold toward the end of my time at sixth form college when we started to learn about DNA. I was fascinated by DNA, but was equally enthusiastic about physical geography. At Imperial College in London, I was initially studying geology in the Royal College of Mines, but soon came to realize I was not as interested as I thought I might be and, for a moment, considered dropping out to return to the farm in Norfolk. My mum suggested seeing if I could switch to biochemistry. I was permitted to switch degrees and it was one of the best decisions I have ever made.

What are your current research interests?

For my degree and first postdoctoral, I worked on generating gene maps in regions of the genome where disease mutations were known to reside. I discovered and published numerous genes that had not been described before. For my second postdoctoral, I switched fields and began to work on epigenetics, with a particular emphasis on X chromosome inactivation, or XCI. XCI is the process that evolved in mammals to deal with the imbalance in the number of X chromosomes between males (who have an X and Y chromosome) and females (who have two copies of the X). If nothing was done, females would essentially have twice the amount of X-linked gene product per cell compared to males. For any of our other chromosomes, 1 through 22, gain or loss of part or a whole chromosome results in severe disease or early lethality in development.

With regards to the X chromosome, this problem is overcome by shutting down one of the two Xs early in female development. XCI is a classic example of epigenetics, the study of changes in organisms caused by modification of gene expression without actually changing the underlying DNA sequence. The inactive X chromosome, Xi, provides an excellent model to investigate how gene silencing is established and maintained. Currently my lab is focused on several aspects of XCI as well as investigating several chromatin proteins linked to the maintenance of Xi.

What would you like the public to know about your research and its importance?

In many ways, what we learn about how genes are silenced on the Xi directly translates to understanding gene silencing on a gene-by-gene basis throughout all chromosomes. Inappropriate gene expression is a common feature of many diseases and a hallmark of cancer. XCI research has contributed significantly to many areas of epigenetic and genomic research.

One of the major impacts of XCI research came from my former postdoctoral supervisor, Dr. Huntington Willard, in the early 1990s. His lab identified a gene in humans that was expressed exclusively from the chosen Xi named X-inactive specific transcript, XIST. Unlike the vast majority of genes that are first made into RNA, which then instructs synthesis of a protein, XIST functions solely at the RNA level. It was the founding member of genes now referred to as long-noncoding RNAs. Remarkably, XIST was found to reassociate with the Xi from which it is expressed and seems to act as a scaffold to recruit gene silencing machinery to the Xi. Other lncRNAs work in a similar manner and many of the proteins they recruit are drivers of cancer, if mutated.

Who are your role models? Are there certain people that have influenced you the most?

I don’t really have a role model per se; however, I have been influenced by numerous people throughout my life. Mrs. Newton, my middle school teacher, had a big influence on me. She was strict, but highly motivating. She pushed me to always give my best effort for everything I do.

On the scientific side, I was most influenced by Dr. Kevin O’Hare, a faculty member in the biochemistry department at Imperial College and expert in fruit fly genetics. In our final year of the degree, we were required to carry out a six-week research project. He showed me how dedicated and self-motivated you needed to be to pursue research. I spent most of my waking hours in the lab and have very fond memories of that time.

What brought you to FSU?

I moved to the U.S. in 1998 to pursue my first postdoc at Harvard Medical School and to continue mapping human genes. It was here that I met my future wife. When she was accepted at Case Western Reserve University to pursue a Ph.D. in mouse genetics, I decided to switch fields to epigenetics for my second postdoc. We both ended up in Dr. Willard’s lab. When he announced he was moving to Duke University Medical School, my wife and I decided to move too. There, I obtained my first faculty position as an assistant research professor. When I saw FSU was hiring a cluster of researchers with an interest in epigenetics, I knew I wanted that position.

What is the best part of your job?

I particularly enjoy teaching graduate students to perform research in the lab. Witnessing their development as young scientists is gratifying, as is seeing them go on to bigger, better things. Among the best parts of being a research scientist is seeing something for the first time and knowing nobody else has ever seen it before. It’s like being an explorer and there are few experiences as rewarding as those discovery moments. I also enjoy teaching genetics and molecular biology to undergraduates. Researching the material for class often drives me to learn new things, and I try to instill my enthusiasm in the topic to the students. Seeing those lightbulb moments when a student suddenly grasps a concept is really rewarding.

What is the most challenging part of your job?

Research funding is certainly one of the hardest aspects. Dealing with rejection is far more common than the exhilaration and relief that comes with the notice you’re getting the award. It’s also tough because you wear many hats in the lab. I’m a lecturer, a researcher, a lab manager, as well as a personnel and finance manager. When things are challenging in the lab, you must be the cheerleader, stay positive, and encourage people. You must also motivate them to forge on, even if inside you feel disheartened.

What do you like to do in your free time?

Pre-COVID, I loved spending time with my family visiting Universal Studios and very much look forward to a time when that might happen again!

If your students only learned one thing from you (of course, hopefully they learn much more than that), what would you hope it to be?

Don’t be afraid to fail, and try to see criticism as an opportunity to better oneself.