Young Investigator Award (Children's Tumor Foundation)

Young Investigator Award (Children's Tumor Foundation) is sponsored by Children's Tumor Foundation (CTF). This award supports early-stage clinical research to advance treatments, interventions, and management for patients with neurofibromatosis (NF), including NF1 and all forms of schwannomatosis.

CTF Young Investigator Awards — NF Research Initiative CTF Young Investigator Awards MPNST Young Investigator Awards The Children's Tumor Foundation's Young Investigator Awards "CTF’s longest running program, the YIA provides two-year funding, commensurate with the National Institutes of Health (NIH), to young scientists early in their careers, bringing them into the NF field and helping to establish them as independent investigators.

Initiated in 1985 by the Foundation, the YIA program was, until 2006, CTF’s sole ongoing grant mechanism. A number of YIAs have made significant research findings and notable publications through this program.

In addition, the YIA program has been a 'seeding mechanism' for researchers and their mentors, who could showcase their Foundation-funded research to secure larger grants from the NIH and the Congressionally Directed Medical Research Program - Neurofibromatosis Research Program (CDMRP-NFRP). CTF’s seeding of the NF field with new talent has been hailed as a key reason for the rapid growth of NF research in recent years."

"The 2017 YIA program has a special emphasis on MPNST, with funding for at least one meritorious application reserved for applicants who focus on the goal of translating genomic information into medical treatments for MPNST. More details are provided in the application form."

The NF Research Initiative is a proud sponsor of the following Young Investigator Awardees: 2019 NFRI-funded Young Investigators “The overall objective of this study is to determine the role of RABL6A, a novel oncogenic GTPase, in regulating the retinoblastoma (RB1) tumor suppressor signaling.

Preliminary work by Ms. Kohlmeyer support the hypothesis that RABL6A drives MPNST pathogenesis by RB1 inactivation, and therefore, the RABL6A-RB1 pathway can be an important, new therapeutic target. This study will determine the mechanisms and biological significance of RB1 pathway regulation by RABL6A in MPNSTs and the value of targeting this pathway to develop novel MPNST therapies.

” University of California, San Francisco Malignant peripheral nerve sheath tumors (MPNSTs) are rare but aggressive tumors associated with NF1. There are currently no molecular biomarkers or targeted therapies available for MPNSTs due to the rarity of these tumors and incomplete understanding of their molecular composition.

The overall aim of Dr. Vasudevan’s proposed work is to use high throughput sequencing in single cells to characterize the molecular heterogeneity in MPNSTs at the DNA, RNA, and protein levels as well as evaluate the functional effect of these changes in primary Schwann cells.

Given the heterogeneous nature of MPNSTs, single cell analyses will be critical to define clinically relevant tumor subpopulations, mutational co-occurrence, and rare genetic variants. 2018 NFRI-funded Young Investigators Van Andel Research Institute Understanding how MPNSTs develop and progress in individuals with NF1 is key to understanding how to effectively treat these aggressive tumors.

The goal of this proposal is to identify how RAS signaling is different between MPNSTs with mutations in NF1, compared to those with mutations in both NF1 and p53 genes. The most important result o fthis study will be the identification of a drug combination that blocks RAS signaling and stops MPNST growth even in p53 tumors. *From CTF website: https://www.

ctf. org/images/uploads/YIA_winners_2010-2018. pdf Dana Farber Cancer Institute The focus of this proposal is to test several drugs specific to the elF4E pathway for antitumor activity and toxicity, and to also identify key proteins that depend on this pathway for expression.

This study will clarify the mechanisms underlying the activity of mTOR inhibitors against NF1-associated MPNSTs, potentially leading to new and complimentary strategies to inhibit these pathways. *From CTF website: https://www. ctf.

org/images/uploads/YIA_winners_2010-2018. pdf 2017 NFRI- funded Young Investigators The focus of my training and research has evolved from basic science to more clinically relevant and applied projects. This progression lead me to an exciting opportunity working on mechanisms of tumor formation and cancer development related to Neurofibromatosis Type 1 (NF1).

My previous work focused on drug sensitivity, protein interactions, and genetic screens in bacteria. I feel there are great opportunities in applying those types of techniques to work on cancer cells. New technologies such as next generation sequencing, gene knockout libraries, and proteomics profiling now let us apply great power to the study of human cells in culture disease modeling.

My current work in the laboratory is focused around both assessing effectiveness of signaling pathway inhibitors and searching for novel pathways to target for therapy in the future. For example, I have developed cell lines deficient in the NF1 gene (mimicking that genetic aspect of the disease). I am currently using these for small molecular/drug and genetic screens as part of the CTF Synodos for NF1 project.

My proposal for the Children's Tumor Foundation Young Investigator Award builds upon this work, allowing us to conduct medium scale combination drug screens to target tumors and identify genetic interaction maps of dependencies in NF1 deficient cells.

lai man (natalie) wu, Phd Cincinnati Children's Hospital Medical Center My major research interests revolve around two distinct, yet intersecting areas: 1) to understand how myelinating glia subtypes (oligodendrocytes and Schwann cells) in the central and peripheral nervous systems develop into myelin-forming cells and how they are regenerated after injury, and 2) how these differentiated cells or their progenitors are transformed into tumorigenic cells under pathological conditions.

Although trained as a developmental biologist, I have had a long-standing interest in how signaling pathway dysregulation contributes to cancer. Specifically, I am fascinated by the remarkable plasticity of Schwann cells in response to injury, which has important implications for cancer. My research background in Schwann cell biology has prepared me well for the transition into Schwann cell-associated tumor research, such as MPNST.

*In February 2018, Cancer Cell published lead author Dr. Lai Man (Natalie) Wu's article Programming of Schwann Cells by Lats1/2-TAZ/YAP Signaling Drives Malignant Peripheral Nerve Sheath Tumorigenesis