He’s Canadian, he plays hockey and he has had a brush with Olympic glory. That’s Gregory D. Longmore, MD, professor of medicine in the Division of Hematology.
No, he didn’t play on an Olympic hockey team. Longmore’s ice time is more recreational than professional, but he once conducted scientific research that cast new light on the athletic prowess of an Olympic gold medalist.
In the early 1990s as a postdoctoral researcher at the Massachusetts Institute of Technology, Longmore found a genetic mutation in a red blood cell hormone receptor that caused mice to produce extra red blood cells. Then, while in Finland to give a scientific presentation, he met a clinician who happened to be studying an extended family with many members having high red blood cell counts.
One of them was Eero Mäntyranta, a famous Finnish athlete who won a dozen or so Olympic and world championship medals in cross-country skiing in the 1960s. Longmore’s genetic discovery intrigued the clinician and a geneticist at the University of Helsinki, Finland, who decided they should look at the same gene in the skier and his kin.
When they ran their tests, they found that Mäntyranta and about 30 of his ancestors and relatives had nearly the same genetic mutation as Longmore’s mice. The skier had enough extra red blood cells to give him a metabolic advantage — and, unfortunately, to make him the target of doping allegations.
Longmore grew up in the mining town of Sudbury, Ontario, and earned an undergraduate degree in biochemistry from the University of Western Ontario, a school he picked because they offered him the chance to play on their football team. That’s right, football — not hockey.
“In Canada, there is kind of a joke, which is actually true in some cases — depending upon what season of the year they are born, kids learn to skate before they walk,” he says. “All the kids play hockey. When I was younger, Canadian youths who wanted to play hockey tried out for a pro farm team at age 14. Unfortunately, at that time, I was small for my age.
“Here’s how they do the tryouts: They put 60 guys on the ice and throw down one puck,” he says. “They say, ‘We’re going to make our first cut in 45 minutes.’ It’s just a bloodbath. I got crushed. After that, I said that I’m not playing hockey anymore. So I played football instead.”
At the university, Longmore took a lot of math and science courses because he considered them easy. He got hooked on research in his second year when he took an organic chemistry course that required him to identify an undisclosed substance.
“I took the night course — in part because I always thought it was cool to be on campus and see all the lights on and people working at night — and there weren’t a lot of students in the class, so I got to work on the problem alone, which gave me the chance to do all the experiments,” he says. “That’s what got me interested in doing laboratory science.”
Longmore graduated at the top of his class and was off to graduate school for a master’s degree in biochemistry at the University of Toronto. He enjoyed being in a lab doing research, but he noticed that the assistant professors looked stressed out and exhausted. Worried about the pressures of the job he was training for, he made a backup plan: medical school.
His choice for medical school was McGill University in Montreal, a city of diverse cultural attractions. After that, Longmore completed a residency in internal medicine and hematology-oncology at Harvard Medical School and then went on to complete postdoctoral training in cell biology at the Massachusetts Institute of Technology before joining the faculty at Washington University School of Medicine.
In addition to running his research laboratory, Longmore works one month per year at Barnes-Jewish Hospital in the hematology consult service, where he diagnoses and manages patients with blood disorders.
“Greg is a great mentor to junior faculty and trainees alike,” says Helen Piwnica-Worms, PhD, the Gerty T. Cori Professor of Cell Biology and Physiology. “He serves on the Medical Scientist Training Program Admissions Committee and is an active member of the Division of Biology and Biomedical Sciences graduate training program.”
The future’s so BRIGHT
Longmore and the members of his laboratory recently became one of five groups that make up the BRIGHT Institute, a part of the BioMed 21 initiative and partially supported by the Siteman Cancer Center. BRIGHT stands for Bridging Research with Imaging, Genomics and High-Throughput Technologies. The institute will use rapid screening methods to identify new anticancer agents.
Piwnica-Worms co-directs the BRIGHT Institute with David Piwnica-Worms, MD, PhD, professor of radiology and of developmental biology and director of the Molecular Imaging Center.
“Greg was asked to be one of the founding members of the BRIGHT Institute because of the high quality of his science, his commitment to mentorship and his collegiality,” Helen Piwnica-Worms says. “He is an outstanding physician-scientist. His medical training gives him a perspective that drives him to investigate problems relevant to cancer onset and metastasis.”
At the BRIGHT Institute, Longmore’s lab will home in on genes that affect cancer’s spread and set up assays to identify compounds that effectively will intervene to stop metastasis.
“Let’s say scientists found out that 10 percent of patients with breast cancer have certain genetic alterations, but we don’t know what the changes mean,” Longmore says. “At the BRIGHT Institute, we can recreate the genetic alterations in our assay systems and find out their effects. Then, using a rapid, unbiased approach, we can look for any proteins, chemicals or drugs that modify those effects.”
Longmore has dual Canadian and American citizenship, and how that came about makes for some good tales.
The Longmore family: (from left) Elizabeth (Bess) Baker, Greg, son Schuyler and daughter Hannah.
“Greg’s a great storyteller, and some of his most entertaining stories are about before he became an American citizen, when he was experiencing the hospitality of the INS (Immigration and Naturalization Service),” says friend and colleague Raphael Kopan, PhD, professor of developmental biology and of medicine in the Division of Dermatology.
“He had the misfortune of losing his green card and ended up in some of those little rooms in which the INS questions people to catch potential terrorists,” Kopan says.
Longmore says that his green card was stolen — twice. As a result, his name was flagged, and he was stopped every time he returned from an overseas trip.
“Imagine you’ve been on a plane for 10 hours and, instead of getting to go home once you land, you’re thrown in a back room for four hours,” he says. “So recently, I obtained American citizenship, and now I can travel on my American passport.”
Another source of tales is Longmore’s hometown, which lies north of Lake Huron and is situated on an ancient meteorite impact crater. During the Apollo program, NASA astronauts trained near Sudbury. Longmore likes to say it was because the landscape was as barren as the surface of the moon, although NASA says it was so the astronauts could learn about shatter cones, a rare rock formation connected with meteorite impacts.
As Longmore describes the area around Sudbury, it’s easy to understand why it might stand in for the moon’s surface. He says that for at least a century, the smelting operations of the town’s mines had discharged sulfur that contributed to acid rain in the region. When combined with the extensive logging of the forests, this greatly diminished the area’s vegetation and exposed its bedrock.
“I’ve hiked in the area,” Longmore says. “There’s not a living thing — not a spider, nothing. The lakes have pHs of about 5.0. You burn your arm if you put it in the water.”
From EPO to metastasis
The mutation in mice that Longmore discovered in the 1990s affects the receptor for the hormone erythropoietin, or EPO (sometimes used illegally by athletes as a performance-enhancing drug). The mutant receptor intensifies signals for red blood cell production.
When he started his research career, Longmore investigated how this receptor regulated red blood cell development and influenced leukemia, and the research gradually evolved to its present focus.
“People in academics are really lucky,” Longmore says. “We can pursue questions for the sake of the pursuit. You want your research to have applicability, but a lot of major discoveries still come from people just asking very basic questions without a practical aim. Sometimes we stumble onto something really important.”
While researching the erythropoietin receptor, he “stumbled” onto a group of proteins that help cells move around. That led to investigations of how cancer cells break away from the primary tumor and spread to other parts of the body.
“Greg’s really a great problem-solver, both in the clinic and on the bench,” Kopan says. “He has the hallmark of a true scientist — he will adopt whatever system necessary to address the question he’s interested in.”
Longmore says that there are many ways to go about scientific research, and it’s important to be open-minded.
“I never had a plan,” he says. “And Washington University really allows flexibility. I was fortunate — I got to do whatever I liked, and it worked out.”
Fast facts about Gregory D. Longmore
Titles: Professor of medicine in the Division of Hematology and professor of cell biology and physiology
Family: Partner Elizabeth (Bess) Baker, PhD, director of the Division of Behavioral Science and Health Education and professor of public health at Saint Louis University; and children Hannah, 20, a junior at Washington University majoring in history in Arts & Sciences, and Schuyler, 18, a senior at Clayton High School who will be a freshman at Kenyon College in the fall
Pastimes: Playing hockey, travel, vacations at the family’s house in the Languedoc region of southern France, and camping on a remote lake in northern Ontario