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$3.5 million funds study aimed at applying precision medicine to rare tumor disorder

Research to focus on causes of diverse symptoms in neurofibromatosis

David Gutmann speaks with a patient
David Gutmann, MD, PhD, speaks with patient Sarah Bess and Stephanie Morris, MD, at the Neurofibromatosis Center at Washington University School of Medicine in St. Louis. Gutmann has received a grant to study the roots of the diversity of symptoms experienced by people with the genetic disorder. (Photo: Robert Boston/School of Medicine)

An international leader in neurofibromatosis research has received a $3.5 million grant to study why people with the same genetic mutation – in this case, a mutation that causes the genetic disorder known as neurofibromatosis type 1 (NF1) – develop markedly different signs and symptoms.

The award — for David H. Gutmann, MD, PhD, the Donald O. Schnuck Family Professor and director of the Neurofibromatosis Center at Washington University School of Medicine in St. Louis — is an inaugural Research Program Award from the National Institute for Neurological Disorders and Stroke of the National Institutes of Health (NIH). The grant provides Gutmann wide latitude; it will allow him to devote half of his efforts for the next five to eight years to solving this research problem.

NF1 can affect almost every organ system in the body. As such, people with NF1 are predisposed to tumors affecting the brain and nerves, as well as to the development of learning and attention problems, bone defects, seizures, cancer and vision loss.

A big question in the field of NF research, according to Gutmann, is how such a diversity of problems can arise in people with the same genetic mutation.

“Variety is the rule for NF1,” Gutmann said. “It is critical that we understand why people are different so we can better predict what’s going to happen next for each patient and know when we need to intervene. Studies like this are essential to implementing precision medicine strategies, not only for people with NF1, but also for patients with other related medical problems.”

The new grant allows his group to approach these questions from many angles. One team is working to expand its NF1 brain tumor modeling efforts – which currently mimic just one kind of tumor – into myriad models, in mice and in human cells, that more fully represent the full spectrum of tumor types found in people with NF1.

Another team is studying brain tumors, not as isolated cells, but rather as ecosystems of many different cell types, all sending molecular signals to interact with and influence each other. Using mathematical tools, the researchers are performing a deep dive into such webs of molecular signals to identify how these networks differ between tumors and healthy tissues, and to find out whether targeting interactions specific to the tumor ecosystem might yield improved therapies for pediatric cancers.

Still others are working on identifying how the NF1 mutation plays out in different types of cells in the brain, as well as developing mouse models to study the cognitive and behavioral symptoms of NF1, such as autism, learning disabilities and attention deficit disorder.

Projects like these are risky but have potential for huge payoffs. The grant is specifically designed to encourage such scientific risk-taking.

“This funding allows me to attack the problem of precision medicine from many angles,” Gutmann said. “We can do things that are much bolder and larger in scope since we do not have to constrain ourselves to what’s immediately achievable.”

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