NF Center and Children’s Tumor Foundation (CTF) Synodos Team Publish Landmark Genomic Study of NF1 Brain Tumors

Dr. Michael Fisher at Children’s Hospital of Philadelphia and Dr. David Gutmann from the Washington University NF Center spearheaded an internal consortium effort to define the genetics of low-grade brain tumors in children with NF1.

In their study, involving 25 centers worldwide, they characterized the genetic changes seen in these tumors, and analyzed the importance of these alterations to patient outcome. Low-grade gliomas from 70 children with NF1 were studied, revealing additional genetic changes beyond NF1 gene mutation. One of these changes involving a mutation in the fibroblast growth factor receptor (FGFR1) was shown to increase the growth of Nf1-mutant mouse tumor cells.

This report was recently published in Acta Neuropathologica.


Fisher MJ, Jones DTW, Li Y, Guo X, Sonawane PS, Waanders AJ, Phillips JJ, Weiss WA, Resnick AC, Gosline S, Banerjee J, Guinney J, Gnekow A, Kandels D, Foreman NK, Korshunov A, Ryzhova M, Massimi L, Gururangan S, Kieran MW, Wang Z, Fouladi M, Sato M, Øra I, Holm S, Markham SJ, Beck P, Jäger N, Wittmann A, Sommerkamp AC, Sahm F, Pfister SM, Gutmann DH. Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1). Acta Neuropathol. 2021 Apr;141(4):605-617. doi: 10.1007/s00401-021-02276-5. Epub 2021 Feb 14. PMID: 33585982

Star NF Center Student Graduates

Anna Wilson graduated from Washington University with Honors and induction into the Phi Beta Kappa Society. Anna completed her honor thesis work in the laboratory of Dr. David Gutmann where she studied sex differences in neurons in mice with a genetic mutation in the neurofibromatosis type 1 gene. Following graduation, Anna will return to the Gutmann laboratory as a Center for Regenerative Medicine Post-Baccalaureate Scholar where she will focus on a new gene implicated in brain development and autism. Many congratulations to Anna!

Gutmann Laboratory Receives A Grant From Ian’s Friends Foundation

The Gutmann laboratory recently was awarded a grant from Ian’s Friends Foundation (IFF) to develop better models of human NF1 low-grade brain tumors (gliomas). In their proposal, this team will be investigating what cells and signals allow human pediatric gliomas to grow in the mouse brain, eliminating a major barrier to the development and deployment of preclinical models for these childhood brain tumors.

IFF partners with and supports research laboratories at leading hospitals and universities around the country focused on the development of new therapeutic methodologies and treatments for pediatric brain tumors. In addition, this organization also works to increase public awareness to the severity of pediatric brain tumors.

May is NF Awareness Month!

Dress in blue in support of NF Awareness on
World NF Awareness Day, May 17th, 2021!

May is NF Awareness Month, join the Washington University NF Center in raising awareness and supporting education and research, throughout the Neurofibromatosis community.

FACTS ABOUT NEUROFIBROMATOSIS

  • A set of complex genetic disorders that affects almost every organ system
  • NF1 affects one of every 3,000 births
  • Occurs worldwide, and in both sexes, as well as all races and ethnic groups

In the Washington University Neurofibromatosis (NF) Center, clinicians and laboratory scientists work together to accelerate the pace of scientific discovery and its application to the care of individuals with NF.

Dr. Caroline Tang Joins The Gutmann Lab

Yunshuo (Caroline) Tang, MD, PhD recently joined the laboratory of David H. Gutmann, MD, PhD, NF Center Director, to investigate vision loss occurring in the setting of NF1 optic gliomas.

Dr. Tang completed her MD and PhD degrees at the University of California, San Francisco, working with Drs. Arturo Alvarez-Buylla, Michael Stryker, and John Rubinstein on the role of specific nerve cell populations in brain plasticity. She then came to Washington University as a resident in Adult Neurology. Dr. Tang was awarded a R25 grant from the National Institutes of Health to work with Dr. Gutmann. Her studies will focus on understanding how NF1-optic gliomas cause vision loss, and how the nerve cells in the eye can be protected. She will also be a team member of the Gilbert Family Foundation Vision Restoration Initiative.

Dr. Tang will also be pursuing clinical fellowship training in Neuro-Ophthalmology.

NF Center Trainee Awarded Francis S. Collins Scholar Award

Nicole M. Brossier, MD, PhD was recently awarded a Francis S. Collins Program in Neurofibromatosis Clinical and Translational Research Award. This program is directed by the Neurofibromatosis Therapeutic Acceleration Program at Johns Hopkins University, and is designed to foster the career development of the next generation of leaders in NF.

Dr. Brossier is finishing her postdoctoral research training in the laboratory of NF Center Director, David H. Gutmann, MD, PhD, where she has focused on understanding the risk factors for brain tumor development in children with NF1. In addition, Dr. Brossier currently cares for children with NF1 brain tumors at St. Louis Children’s Hospital.

We extend our congratulations to Dr. Brossier, who is the second Francis S. Collins Scholar from the NF Center, joining Dr. Angela C. Hirbe from Medical Oncology.

NF Clinical Trials Consortium Reports Vision Stabilization Following Everolimus Therapy

The NF Clinical Trials Consortium recently published a study examining vision in children with NF1 and optic pathway gliomas (OPGs) following treatment with Everolimus.

Leveraging preclinical studies from the Gutmann laboratory demonstrating that mouse Nf1 optic glioma growth is controlled by activated RAS operating through the mechanistic target of rapamycin (mTOR) protein.  Everolimus is an inhibitor of mTOR. Following treatment with Everolimus, vision (visual acuity) was stable or improved in over 90% of children with NF1-OPG.

Future studies involving larger numbers of patients are currently being planned.


Ullrich NJ, Prabhu SP, Packer RJ, Goldman S, Robison NJ, Allen JC, Viskochil DH, Gutmann DH, Perentesis JP, Korf BR, Fisher MJ, Kieran MW; NF Clinical Trials Consortium. Visual outcomes following everolimus targeted therapy for neurofibromatosis type 1-associated optic pathway gliomas in children. Pediatr Blood Cancer. 2020 Dec 18:e28833. doi: 10.1002/pbc.28833. Online ahead of print. PMID: 33336845

Heidary G, Fisher MJ, Liu GT, Ferner RE, Gutmann DH, Listernick RH, Kapur K, Loguidice M, Ardern-Holmes SL, Avery RA, Hammond C, Hoffman RO, Hummel TR, Kuo A, Reginald A, Ullrich NJ. Visual field outcomes in children treated for neurofibromatosis type 1-associated optic pathway gliomas: a multicenter retrospective study. JAAPOS. 2020 Nov 20:S1091-8531(20)30228-7. doi: 10.1016/j.jaapos.2020.07.013. Online ahead of print. PMID: 33221469 

Ullrich NJ, Prabhu SP, Reddy AT, Fisher MJ, Packer R, Goldman S, Robison NJ, Gutmann DH, Viskochil DH, Allen JC, Korf B, Cantor A, Cutter G, Thomas C, Perentesis JP, Mizuno T, Vinks AA, Manley PE, Chi SN, Kieran MW. A phase II study of continuous oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1-associated pediatric low-grade glioma: a Neurofibromatosis Clinical Trials Consortium study. Neuro Oncol. 2020 Oct 14;22(10):1527-1535. doi: 10.1093/neuonc/noaa071. PMID: 32236425

NF Clinical Trials Consortium Study Reveals New Vision Problems in Children with NF1 Optic Gliomas

As part of the NF Clinical Trials Consortium study on vision function after treatment for NF1-optic glioma, lead author, Dr. Gena Heidary, discovered additional vision deficits in children. While most clinical trials focus on visual acuity, the ability to read numbers or letters at a distance, this new study found that children also have problems seeing the entire area of sight, termed the visual field.

In this new report, Dr. Heidary found that nearly three-quarters of children had visual field defects following treatment for an optic glioma. Moreover, over 80% of children with visual field deficits prior to treatment either had no improvement or worsening after treatment. Future NF1-optic glioma clinical studies will incorporate visual field testing and will aim to determine how visual acuity and visual field defects are related.

This report was published in the Journal of the American Association for Pediatric Ophthalmology and Strabismus.


Heidary G, Fisher MJ, Liu GT, Ferner RE, Gutmann DH, Listernick RH, Kapur K, Loguidice M, Ardern-Holmes SL, Avery RA, Hammond C, Hoffman RO, Hummel TR, Kuo A, Reginald A, Ullrich NJ. Visual field outcomes in children treated for neurofibromatosis type 1-associated optic pathway gliomas: a multicenter retrospective study.  J AAPOS. 2020 Nov 20:S1091-8531(20)30228-7. doi: 10.1016/j.jaapos.2020.07.013. PMID: 33221469

NF Clinical Trials Consortium Identifies a New Therapy for Plexiform Neurofibromas

A recent study spearheaded by Dr. Michael Fisher at Children’s Hospital of Philadelphia and Dr. D. Wade Clapp at Indiana University found that cabozantinib as an effective therapy for NF1-associated plexiform neurofibromas.

Using a preclinical mouse model of plexiform neurofibromas, this team showed cabozantinib was effective at reducing mouse tumors. Leveraging these exciting findings, they launched a Phase II study in patients older than 16 years of age with progressive or symptomatic plexiform neurofibromas. They found that no patient had continued tumor growth on cabozantinib, and many reported reduced pain symptoms.

This landmark study underscores the importance of preclinical models to the identification of promising therapies for patients living with NF1 tumors.

The report was recently published in Nature Medicine. PMID: 33442015


Fisher MJ, Shih CS, Rhodes SD, Armstrong AE, Wolters PL, Dombi E, Zhang C, Angus SP, Johnson GL, Packer RJ, Allen JC, Ullrich NJ, Goldman S, Gutmann DH, Plotkin SR, Rosser T, Robertson KA, Widemann BC, Smith AE, Bessler WK, He Y, Park SJ, Mund JA, Jiang L, Bijangi-Vishehsaraei K, Robinson CT, Cutter GR, Korf BR; Neurofibromatosis Clinical Trials Consortium, Blakeley JO, Clapp DW. Cabozantinib for neurofibromatosis type 1–related plexiform neurofibromas: a phase 2 trial. Nat Med. 2021 Jan;27(1):165-173. doi: 10.1038/s41591-020-01193-6. Epub 2021 Jan 13. PMID: 33442015 Clinical Trial.

Ji-Kang Chen Joins the Gutmann Laboratory

Ji-Kang Chen, MS recently joined the research laboratory of NF Center Director, David H. Gutmann, MD, PhD, as a Research Technician. He completed his master’s degree at Taiwan National Yang-Ming University, where he studied how hippocampal nerve cell (neuron) work in the brain.

Bringing his expertise in neuron biology to the Gutmann laboratory, Ji-Kang is studying how Nf1 mutation changes the ability of brain and peripheral nerve neurons to control tumor formation and growth. We are delighted to have him spearhead this important project.