Sep 29, 2017 2:00 PM

Author: Alyssa Geisler

The Engel Lab: Helene Lucente, David McClellan, Mattie Casey, Diana Bareyan, and Michael Engel. (Not pictured: Wenxiang Sun and Chris Ours)

“As a physician-scientist, the patients I’ve treated who haven’t made it are always in the back of my mind, moving my laboratory work forward,” says Michael Engel, MD, PhD, an associate professor in the division of pediatric hematology/oncology and the department of oncological sciences at the University of Utah, and a Huntsman Cancer Institute (HCI) investigator.

Unfortunately, pediatric cancer research is not funded at the level of many adult cancers.

“Our capacity for solving medical problems, like cancer in a kid, is no longer limited by knowledge, or passion, or commitment, or energy,” Engel continues. “It’s limited by resources. Children with cancer need us to be their voice, and to encourage the federal and private funding that can eradicate these diseases. At HCI and the University of Utah, we are taking the lead to really focus on these.”

By bringing an equal focus to pediatric cancers, Engel believes medical research can make significant advances in understanding and treating childhood cancer.

The patients Engel has treated for childhood leukemia are a driving force for his scientific work. His lab studies the molecular details that lead to the development of leukemias and then leverages that information to combat them.

“Our cells are really smart. They’re hard-wired to obey certain rules, and generally only divide when they are given permission. This keeps them from expanding out of control,” Engel says. Cancer cells, however, have learned how to break those rules.

When a growth signal is constantly turned on that would normally only be on for a brief period of time, normal cells interpret that as a problem and will self-destruct. In essence, the malfunctioning cell dies so that the whole organism will survive. But cancer cells find ways to adapt to these irregular signals. They stay alive when they shouldn’t, and eventually can lead to cancer.

“We call these pro-survival adaptations,” Engel explains. “They are like a cancer’s Achilles’ heel.” If scientists can understand the pro-survival adaptations that allow cancer cells to survive, they can change the signal that supports the cancer cell into the thing driving its death.

Engel’s lab has found that a signaling pathway called Notch malfunctions in T-cell acute lymphoblastic leukemia (T-ALL). Notch hijacks a pro-survival mechanism comprised of two proteins, GFI1 and LSD1, that work together to enable T-ALL cell survival. They are now developing a new drug, in collaboration with Sunil Sharma’s group, that blocks the pro-survival function of the GFI1—LSD1 partnership.

“T-cell leukemia cells are exquisitely sensitive to this drug. It’s like a bomb goes off when you treat them,” he says.

Engel says this type of collaboration is what cancer centers are for. “The whole building is filled with people who see the same problem through different lenses. When you meet in the elevator or sit down over lunch, you tend to develop new partnerships that enable you to do things as a group that you could never do as an individual.”

Now, his lab is working hard to move the drug they’re testing into the clinical space.

“You probably get one or two shots in your whole career to take something from an idea floating around in your brain and see that potentially influence patients’ lives in a positive way,” he says. “And do be able to do that for children... it doesn’t get any better than that.”

Alyssa Geisler

Huntsman Cancer Institute

childhood cancer aya cancer leukemia cancer research

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