No journey too large or too small

Sheila Stewart enjoys treks through microscopes and mountains

Whether she’s following a tantalizing thread of scientific evidence in the laboratory or trekking to remote corners of the world with her husband, Jake, Sheila Stewart loves epic journeys.

Stewart, Ph.D., assistant professor of cell biology and physiology, speaks with equal enthusiasm of her studies of molecular structures on the ends of DNA and of the time she had to confront a “bird spider whose body was bigger than the size of my head.”

Sheila Stewart, Ph.D., and Lionel Guittat, Ph.D., a postdoctoral student in her laboratory, discuss a readout of protein expression in cancer cells.
Sheila Stewart, Ph.D., and Lionel Guittat, Ph.D., a postdoctoral student in her laboratory, discuss a readout of protein expression in cancer cells.

The former effort may lay the groundwork for opening up new fronts in the war on cancer; the latter proved to be unavoidable as she and her husband hiked to what they had heard would be excellent scuba diving territory off the north end of the Japanese island of Okinawa.

“Jake and I will go to any length to get to a cool dive spot, and while he was stationed at Okinawa, we had heard that best scuba diving was only accessible on foot through the northern jungle,” says Stewart, 37.

After a mile-and-a-half of hauling two tanks and all their dive gear through the steamy tropical landscape, Stewart heard the ocean in the distance.

“I just happened to look up, and above my head and the only path to the ocean through the jungle was a bird spider,” she remembers. “And this guy was on his web hovering about 10 feet over where I had to walk, and that made me hesitate, but only for a moment.”

She went through and enjoyed an amazing dive. Other travel highlights have included a trip to Peru to visit the ruins of Machu Picchu; seeing the sights in Vietnam; bungee jumping in Costa Rica; and hiking to the top of the world’s tallest freestanding mountain, Mount Kilimanjaro in Tanzania, Africa.

Sheila Stewart and her husband, Jake, atop the summit of Mount Kilimanjaro in Tanzania, Africa.
Sheila Stewart and her husband, Jake, atop the summit of Mount Kilimanjaro in Tanzania, Africa.

“They begin the final ascent at midnight so you reach the peak of Kilimanjaro right at sunrise,” Stewart recalls. “That was the most amazing sunrise I’ve ever seen in my life.”

Despite the remarkable travel history she’s already accumulated, Stewart notes, she still has a lot of journeying to do to catch up to her father-in-law, Zeke, a newspaper editor who has served as a foreign correspondent and as the editor of the travel section.

“Zeke’s been to many, many exotic places, and it seems like no matter where we go he always has some useful advice to offer us,” Stewart says.

Life in the lab has biological concepts and conundrums as its landmarks, but they’re still just as fascinating to Stewart, who often speaks of her joy in being able to “follow the science” wherever it leads.

“It’s not that what I discover today is going to save someone’s life tomorrow,” Stewart says. “But I have positioned my lab in such a way that I can both get into the nuts and bolts of really understanding how something works and know that the questions we answer will one day have an impact on human health.”

Stewart came to Washington University in 2003 and quickly won notice by becoming the University’s first faculty member to win a Kimmel Scholar Award. The awards are presented annually to a handful of the nation’s most promising young cancer re-searchers by the Sidney Kimmel Foundation for Cancer Research.

“The Kimmel Scholar award is a very prestigious award, and Sheila has been a tremendous addition to the department and the University,” says Helen Piwnica-Worms, Ph.D., professor of cell biology and physiology. “She has so much energy and passion for her science and is a wonderful mentor to her students.”

As a graduate student at the University of California, Los Angeles, Stewart studied HIV and other retroviruses. But she became interested in the extraordinary properties of cancer cells during her postdoctoral studies at the Whitehead Institute for Biomedical Research in Massachusetts. Much of her research is now focused on how cancer cells beat a built-in limitation on the number of times most cells can reproduce. That limitation is linked to cap-like structures on the ends of DNA known as telomeres.

“As the chromosomes are replicated when a cell reproduces, the telomere gets a little teeny bit shorter,” Stewart explains. “And eventually it gets a little too short, and that’s when the cell is forced to stop reproducing. We call such cells senescent cells.”

Scientists think this limitation may be a built-in anti-tumor mechanism: if an incipient cancer cell tries to reproduce too quickly and too often, it depletes the telomeres and is forced to stop dividing. However, an estimated 90 percent of all cancer cells activate telomerase, a DNA repair enzyme that helps maintain the telomeres during DNA replication. Because their telomeres are regularly repaired, these cancer cells can continue to reproduce indefinitely.

Sheila Stewart

Title: Assistant professor of cell biology and physiology

Years at University: Three

Hobbies: Scuba diving, traveling, cooking

Stewart’s lab has been working to better understand telomere structure, how telomerase functions, and how telomere dissolution shuts down cell replication. She hopes to provide the information necessary to develop new cancer treatments that inhibit the effects of telomerase.

“Cancer is the result of numerous mutations, and to effectively treat it you want to simultaneously attack it on as many fronts as possible,” Stewart explains. “Inhibiting telomerase probably won’t ever be used by itself as a tumor therapy, but it does have the potential to augment the effects of more traditional treatments such as chemotherapy.”

Senescent cells have also recently begun showing up in another potential new front in the war on cancer. Cancer specialists have begun to theorize that cells halfway between normal and cancerous may get a final boost toward becoming cancers from their interactions with nearby normal cells. Early evidence suggests that senescent cells may be among the normal cells whose interactions with precancerous cells supply that final boost toward cancer.

“We’re going to be looking into whether we can prove this and identify the key interactions between senescent cells and precancerous cells,” Stewart says.

Stewart doesn’t converse so much as she verbally spars — she loves to say daring and provocative things, but always with good-natured glimmers of amusement clearly visible on her face. She begins a conversation about her research program, for example, by asking, “So, you want to hear about how we’re trying take over the world?”

Heather True-Krob, Ph.D., assistant professor of cell biology and physiology, came to the department the same year as Stewart. She jokes that her colleague and friend’s energy levels are so high she “would rather go to the gym than sleep.”

“Until you get to know her and realize that she is very focused, what stands out the most about Sheila is that she has so much energy,” True-Krob says. “One of her greatest qualities, though, is that she is a very generous person who would never say no to a friend or acquaintance needing help.”

Piwnica-Worms notes that Stewart is a “fabulous cook.” As they traveled the globe, Stewart and her husband, a former Marine Harrier pilot who now helps design flight training systems for Boeing, became interested in cooking world cuisine when they returned home.

Under the heading “fun stuff,” Stewart’s Web site includes recipes for the Indian dishes aloo gobi, sag paneer and chole.

“Cooking’s a nice break from the precision of the lab,” Stewart says. “In the lab, every measurement has to be exact, but in the kitchen you have a little more license to say, throw in an extra tablespoon or two of a favorite ingredient.”

Favorite cuisines at the Stewart household include sushi, Indian food, seafood and a Spanish rice dish called paella. Stewart boasts that they recently purchased a “fire ring,” a large grill-like device with two independently controllable ring-shaped burners. The device is seen as an essential cooking tool by paella connoisseurs.

Stewart has her sights set on the southern tip of South America as the next exotic vacation destination but may have to postpone that for a bit because she is expecting her first child in May.

Noting that her pregnancy has kept her from scuba diving, Stewart jokes, “As soon as our baby can swim, I think we’re going to get it a scuba diving regulator.”