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Children’s Tumor Foundation Invests Nearly $700,000 in NF1 Young investigator Awards and Drug Discovery Initiatives

New projects and drug development to focus on MPNSTs, pseudarthrosis, breast cancer risk, biomarkers, and learning disorders

The Children’s Tumor Foundation (CTF) announced an investment of nearly $700,000 in NF1-focused projects through the CTF Discovery Fund, a collection of grants that support researchers and clinicians engaged in novel and fundamental NF investigations. These new projects will focus on MPNSTs, pseudarthrosis, breast cancer risk, biomarkers, and learning disorders.

The Discovery Fund comprises multiple funding mechanisms, including the Young Investigator Awards and the Drug Discovery Awards. We are pleased to announce the recipients of this latest round of funding:


Young Investigator Awards (YIA):

Mechanisms of MPNST Metastasis Alexa Sheehan, The University of Iowa
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with high metastasis rate and poor clinical prognosis in NF1 patients. The present study will test newer formulations of Lox inhibitors, which are more specific and less toxic, to decrease MPNST metastasis. Since PRC2 loss also changes global gene expression in MPNSTs, this study will also test a second category of drugs called epigenetic modulators for their effect on metastasis. Overall, this study will determine if targeting Lox proteins induced by PRC2 loss is a viable treatment option for patients with metastatic MPNST.

A skeletal stem cell basis and novel therapeutic approaches for fracture healing defects in Neurofibromatosis type 1 Jun Sun, Weill Medical College of Cornell University
Pseudarthroses or non-healing fractures are major skeletal manifestations of NF1 that contribute to the overall pain and disability associated with this disorder. MEK inhibitors, which are effective against NF1 tumors, are not clearly known to treat the skeletal problems in NF1.  This group previously reported that loss of NF1 function causes abnormal activation of a protein kinase MEKK2 within the signaling pathway downstream of NF1 in skeletal cells. They further showed that MEKK2 inhibition is effective in healing fractures in mouse models of skeletal NF1. The present study will investigate the mechanism by which NF1 loss in skeletal stem cells contributes to impaired fracture healing, MEKK2’s role in this process, and the effect of MEKK2 inhibitors in reversing this effect. This study will also develop a method to selectively deliver drugs to the non-healing fractures, thereby avoiding unwanted side effects in other organs. Along the way, the study will develop new preclinical models for skeletal NF1.

Risk factors and characteristics of NF1-associated cancer Roope Kallionpää, University of Turku, Finland
NF1 increases the risk for various cancers such as MPNST and breast cancer, and such cancers are a major cause of premature deaths among individuals with NF1. The three main objectives of this study are determining the risk for multiple cancers in individuals with NF1, determining the role of family history in cancer risk in NF1 and correlating it with NF1 gene variants, and identifying breast cancer characteristics unique to NF1. The study will analyze a Finnish cohort of over 1800 NF1 patients, for whom data are also available through other comprehensive Finnish population and disease registers. Results from this analysis can lead to improved strategies of personalized care for NF1 patients.

CENPF as a biomarker and therapeutic target for NF1-associated MPNST Aditya Sheth, Indiana University
Preliminary data show that the CENPF gene, which codes for the Centromere Protein F (CENPF), is activated when PNFs progress into MPNSTs. Higher levels of CENPF are detected in MPNSTs compared to PNFs, suggesting that this gene may promote progression of benign PNFs into aggressive cancerous MPNSTs. Further, loss of CENPF kills MPNST cells suggesting its potential use as a therapeutic target for MPNST. Using a larger tumor sample set and additional cell lines and animal models, this study will evaluate whether increased CENPF correlates with PNF progression and whether CENPF loss prevents MPNST formation. These studies will provide a preclinical rationale for using CENPF in assessing patient risk for MPNST as well as the development of a targeted MPNST treatment.

Investigating the link between sensory and social deficits in a Drosophila model of Neurofibromatosis type I Jadwiga Bilchak, University of Pennsylvania
NF1 is characterized primarily by tumors of the nervous system, but in addition, up to 50% of patients experience learning and social communication deficits. The present study will investigate the molecular mechanisms in sensory neurons affected by Nf1 mutation and how disrupted sensory messages are transformed in the brain to shape behavior. The results from this study will shed light on how NF1 affects behavioral circuits in the brain and how this relates to differences in social interactions.


Drug Discovery Initiative (DDI):

Identification of drugs targeting epigenetic regulators in an iPSC-based 3D MPNST model Eduard Serra-Arenas, Health Sciences Research Institute of the Germans Trias i Pujol Foundation, Spain
The Serra-Arenas group has developed a new cell-based model system for NF1 using induced pluripotent stem cells (iPSCs), cells that have the capacity to differentiate into any cell type. Using this system, they generated iPSCs with mutations in multiple genes like in MPNSTs. These cells can be grown in 3D spheres and exhibit the genetics and biological characteristics of MPNSTs. In this study they propose to use this new 3D MPNST model system to rapidly screen ~600 compounds. Based on the results, a selected group of compounds will be tested further as single agents or in combination with other known drugs to identify new therapies for MPNST.


The Young Investigator Award (YIA) provides seed funding to attract early-career researchers to the field and to produce data to secure larger grants, such as from the NIH and CDMRP NFRP. Several former YIAs are now leaders in the NF research and clinical communities. In fact, CTF’s ‘seeding’ of the NF field with new talent has been hailed as one of the key reasons for rapid advancements in NF research in recent years.

The Drug Discovery Initiative (DDI) stimulates NF drug discovery by funding researchers proposing to investigate novel or repurposed therapies for NF or to develop tools that support such research.

In addition this year, over three-quarters of a million dollars is also being invested in research projects focused on all types of schwannomatosis, including NF2-related schwannomatosis. Click here to read about these investments. 

Click here to learn more about funding opportunities from the Children’s Tumor Foundation.