Discovering cancer's molecular switches

David Walterhouse and Ben Xu

Each year, cancer claims the lives of more than 2,200 children in the U.S. At Children’s Memorial Research Center, scientists are working on a number of projects aimed at uncovering the basis of cancer and developing new and more effective therapies to treat it. One of the more intriguing areas being studied by investigators like physician-scientist David Walterhouse, MD, is how normal cells receive “signals” that cause them to turn into cancer cells.

Walterhouse, an attending physician in Children's Memorial Hospital’s Division of Hematology, Oncology and Stem Cell Transplantation and an associate professor of pediatrics at Northwestern University's Feinberg School of Medicine, is studying the Sonic Hedgehog-GLI gene pathway. The gene pathway is so named because fruit flies, where the pathway was first discovered, carrying mutations in this gene pathway develop projections over their backs resembling a hedgehog’s quills.

This signal transduction pathway begins outside of the cell but signals the inside of the cell and gives it specific instructions on what to do, says Walterhouse, who collaborates closely with Philip Iannaconne, MD, director of Developmental Biology at the research center and the George M. Eisenberg Professor in Developmental Systems Biology.

Walterhouse is trying to better understand the role this pathway plays in specific types of cancer, including brain tumors, skin cancer, kidney tumors and sarcomas. Normally this pathway functions during embryonic development, and becomes inactive after birth. But sometimes those signals become reactivated during childhood or later in life, resulting in the development of cancer cells. By finding out which genes are specifically activated by this process, how the gene pathway flips “molecular switches” to turn a normal cell into a cancer cell, and how it causes a tumor to spread, Walterhouse hopes new therapies may be discovered to inhibit cancer development.

“It’s a basic science question as well as a developmental biology question,” says Walterhouse, the George M. Eisenberg Research Scholar in Developmental Systems Biology. “I’m an oncologist, and my interest in developmental biology is that all childhood cancers are really developmental defects at a cellular level. We have to understand how these pathways work together to “signal” cells to grow, stop growing or turn into something else. Only if we can accomplish this and understand how these pathways work normally can we recognize what goes wrong in cancer, which may ultimately lead to the development of treatments for certain forms of cancer.”

Such research studies are expensive, though, and in a climate where federal funding is ever shrinking, Walterhouse says public support is essential. “Philanthropy plays such a crucial role in sustaining labs such as mine, and I’m so grateful to all who support our work,” he says.

Walterhouse is also an expert on rhabdomyosarcoma (RMS), a cancerous tumor that originates in the soft tissues of the body and is the most common type of sarcoma in children. He serves as a study chair for the RMS Committee of the Children’s Oncology Group, consults on patients and conducts seminars around the world on the disease.

Another of Walterhouse’s priorities is the training of tomorrow’s physician-scientists. He is the director of the fellowship program for the hospital’s Division of Hematology, Oncology and Stem Cell Transplantation for fourth-, fifth- and sixth-year clinician residents.

“Training young physicians is very important, because they are the future,” he says. “Pediatric oncology is a very research-oriented field, and we are training the next generation of innovators – the individuals who will be developing new treatments for cancer.”

Research into Developmental Biology at Children’s Memorial Research Center is supported by The Chicago Community Trust; George M. Eisenberg Foundation for Charities; Little Heroes Pediatric Cancer Research Foundation; Mr. & Mrs. James G. Manzk; Medical Research Institute Council; Medical Research Junior Board; North Suburban Medical Research Junior Board; and Paige Nicole White Pediatric Cancer Foundation, among others.


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