Trainor Lab

Paul Trainor, Ph.D.

Investigator

Professor, Department of Anatomy & Cell Biology
  The University of Kansas School of Medicine

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Paul Trainor, Ph.D., spent his childhood at the beach, not playing with a chemistry set.

“I wasn’t a bug collector—I was too busy playing sports,” says Trainor, water lover and native of Sydney, Australia. But as a University of Sydney undergrad he developed what he calls a “morbid fascination with freaky animals” and an appreciation of the power of genetics after learning that Hox gene mutations could produce fruit flies with legs where antennae should be.


Migrating neural crest cells (shown in green) in a mouse embryo.

Image: Courtesy of Dr. Amanda Barlow, Trainor Lab

That curiosity fueled his present intense interest in how the vertebrate head and face is formed. Where better to acquire the tools necessary to pursue that interest than with renowned embryologist Patrick Tam, at the Children’s Medical Research Institute at the University of Sydney.

During his Ph.D. thesis work in Tam’s lab, Trainor learned cell labeling and manipulation techniques required to trace how embryonic cells migrate to form the head and face. In 1994 and 1995 Development papers he reported that in mouse neural crest cells—a population of cells streaming from the neural tube, the embryo’s precursor to the central nervous system—and adjacent mesodermal cells move toward common destinations in the head, suggesting that traveling “in tandem” is necessary for both cell types to direct formation of facial bone, cartilage, connective tissue, and peripheral neurons.

Awarded a Ph.D. in 1996, Trainor moved to London to postdoc with Robb Krumlauf at the National Institute of Medical Research (NIMR), a satisfying decision on multiple levels. “It is an Australian rite of passage to take time to travel through Europe,” he says, “I was highly motivated.” At that time Krumlauf was doing pioneering work on the molecular basis of how the hindbrain patterns facial structures, making his lab an ideal travel destination.

In the Krumlauf lab Trainor exploited transplantation techniques to transpose or swap neural crest precursors from various positions in the hindbrain. Using Hox gene expression as a read-out, he demonstrated that the fates of cranial neural crest cells are influenced by mesodermal tissues they encounter en route to the face. These studies challenged the idea that crest cells are pre-programmed to “know” what structures they will form and were reported back-to-back in Nature Cell Biology papers in 2000.


Craniofacial bone development in 18.5 day-old mouse embryo. Bone is shown in red, cartilage in blue.

Image: Courtesy of Dr. Natalie Jones


 

Trainor came to Stowers as assistant investigator in 2001 and became an associate in 2008. His respect for Krumlauf outweighs any hesitation one might have in working at a place led by your former advisor. (Robb Krumlauf is Stowers’ Scientific Director.)

“At NIMR, Krumlauf was the biggest cheerleader for his lab and gave us all so much credit,” says Trainor. “I knew he would do the same at Stowers, but on a bigger scale.”

Trainor has recently focused on pathologies emerging from neural crest defects, known collectively as neurocristopathies. “One of the first things an embryo does is start making a head,” he says. “Many cell types have to be integrated, so from an anatomical perspective there is a big likelihood of encountering problems.”

In fact, about one third of all birth defects are accompanied by craniofacial anomalies, most due to abnormal neural crest development or migration. One of interest to Trainor is Treacher Collins Syndrome (TCF), marked by jaw, palate and ear defects. In humans, TCF is caused by mutations in the Tcof1 gene, which encodes a nucleolar protein. To determine why its loss is so disastrous to neural crest cells Trainor has in recent years collaborated with Mike and Jill Dixon of the University of Manchester in the UK.


Bone development in 14.5 day-old mouse embryo. Bone is shown in red, cartilage in blue.

Image: Courtesy of Dr. Natalie Jones

In a 2006 PNAS study, they reported that in mice when Tcof1 is mutated, many neural stem cells die. Since neural stem cells are the precursors of neural crest cells, the embryo cannot produce enough neural crest cells to properly build the head and face. And 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 defects, not just repair them,” says Trainor. “And it’s great justification for basic research.” The March of Dimes agreed, awarding him a Basil O’Connor award in 2003.

His lab also conducted a mutagenesis screen in mouse searching for novel genes regulating cranial crest development. A 2011 Genesis study identified 10 novel mouse mutants showing differing craniofacial anomalies, 8 of which the lab has identified molecularly. 

One gene encodes Rdh10, an enzyme regulating vitamin A metabolism. The mice themselves—called trex mice—are severely deficient in the vitamin A metabolite retinoic acid (RA), a factor regulating multiple genes critical for embryogenesis—including some Hox genes. Trex mice also show limb and cardiac abnormalities. “Too much or too little RA is extremely detrimental to embryonic development,” says Trainor, citing the strong correlation between use of RA-containing anti-acne creams by pregnant women and birth defects.

The screen required concerted and intense effort by the entire lab and Trainor is happy not only about the outcome, but (sounding a little like his postdoctoral advisor) also the success it will bring to people in his lab. But Trainor encourages them to lead a balanced life, leading by example. He still cycles, does triathlons and plays water polo—anything, he says, to keep him outdoors.

“For our lab website I encouraged people not to use a picture of themselves in the lab,” says Trainor, no fan of the white coat profile pic. “It’s nice to see that people in labs are real people.” His apparently are—lab members are shown riding camels, working out (with snakes), smiling with their families, and even kissing! And the boss? He’s looking relaxed and happy in Sienna, Italy, still fulfilling his travel desires.