BSc, Genetics and Biochemistry, University of Sydney, Australia
PhD, Developmental Biology, Children’s Medical Research Institute, University of Sydney, Australia
Today Paul Trainor, PhD, is regarded as a leader in the fields of craniofacial, neural crest cell, and developmental biology by his peers in the international scientific community. Growing up in Australia, as a University of Sydney undergrad, Trainor learned that genetic manipulation could produce fruit flies with too many wings or misplaced antenna. He’s been hooked on genetics and embryology ever since.
After graduating with his BS in genetics and biochemistry, Trainor did his PhD thesis work in the lab of renowned embryologist Patrick Tam, PhD, at the Children’s Medical Research Institute of Sydney. There he became interested in how the vertebrate head and face are formed—the focus of his research today. Awarded a PhD in 1996, Trainor moved to London to postdoc at the National Institute of Medical Research with Robb Krumlauf, PhD (now a Stowers investigator and scientific director emeritus). Krumlauf was a pioneer in how part of the brain, called the hindbrain, patterns facial structures, making his lab an ideal place for Trainor to launch his work. Trainor joined the Stowers Institute in 2001.
While he’s dedicated to his research, living a well-rounded life is important to Trainor. In his spare time, he enjoys spending time traveling, swimming and cycling with his family, and playing water polo with a team in Kansas City. During the summer, he also participates in triathlons. Trainor encourages his team members to follow his example and take frequent breaks from the lab. Not a fan of the white lab coat photo, his lab’s website features snapshots of his team in their favorite places, doing activities they love. Trainor explains that research is like reading a long and engrossing book – when you get to an end of a chapter, sometimes you need to put it down, take a break, and do something else fun for a while.
“I believe that even individuals who are very passionate about their work need to recharge, take a break, and refresh. It’s all about balance,” he says.
The Trainor Lab studies neural crest cells, a population of cells born early during embryonic development, in laboratory animals, including mouse, zebrafish and chameleons. They migrate from the primitive embryonic brain and spinal cord to help form the face, heart, and gut. Neural crest cells generate much of the bone, cartilage, and connective tissue of the head and face as well as neurons and glia in the peripheral nervous system—contributing to nearly every organ in the body.
Abnormalities in neural crest cell development can lead to congenital birth defects including craniofacial anomalies such as Treacher Collins syndrome (TCS), cardiac defects such as persistent truncus arteriosus and gastrointestinal tract malformations such as Hirschsprung’s disease (HD).
Trainor and his team have identified many genes and molecular mechanisms important to craniofacial development. Much of the Trainor Lab’s work has focused on TCS. The developmental disorder, characterized by malformation of the ears, eyelids, cheekbones, and jawbones, rose to prominence with the book and movie Wonder, in which the main character has TCS. Children with this condition often face years of reconstructive surgery that is never fully corrective. In a 2006 PNAS study, the Trainor Lab discovered that when the gene Tcof1 is mutated in mice, many neural stem cells die, preventing the embryo from producing enough neural crest cells to properly build the head and face. Then in a 2008 Nature Medicine paper, they showed that blocking the p53 gene, which promotes cell death, restores neural crest cells and rescues craniofacial abnormalities in Tcof1-deficient mice. “This work shows that we can intervene and prevent birth defects, not just repair them,” says Trainor. “And it’s great justification for basic research.”
The Trainor Lab also studies neural crest cells and formation of the enteric nervous system which is responsible for gastrointestinal function. In two studies published in Human Molecular Genetics in 2012 and 2013, they demonstrated that the microenvironment of the embryonic gut is critically important for proper enteric nervous system formation, and then identified two genetic modifiers of neural crest cell development and Hirschsprung’s disease in an animal model. More recently, Trainor and his team are investigating the importance of gene-environment interactions in embryo development. In 2007 in Genes and Development they reported the identification of the Rdh10 gene as being essential for vitamin A metabolism and subsequently showed in follow-up publications that vitamin A is essential for proper lip, palate, ear, heart, limb and gastrointestinal development.
The Trainor Lab often attends retreats for individuals with Treacher Collins syndrome and their families to discuss their latest findings and explain the genetics behind the disorder, and to listen to parents share their stories and challenges. Meeting the parents motivates the team to do their best research.
“Our ultimate goal is to determine why specific birth defects occur in the first place and to identify the genes and the environmental factors or agents that cause them,” Trainor says. “If we can understand the origin and development of congenital disorders in enough depth, we may be able to come up with creative ways to prevent them from occurring.”