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The application process for the 2012 Young Investigator Award program is NOW OPEN! Please note the deadlines below for the pre-application and full application.  Please be sure to carefully read the guidelines of the  application process.

YIA SALARY LEVELS INCREASED FOR 2012!
We are delighted to announce that all salary levels for 2012 have been significantly increased over 2011 levels!

HOW TO APPLY FOR A 2012 YIA: IMPORTANT NOTES ABOUT THE PROCESS

The 2012 YIA application process is in two stages:

1.    YIA Pre-Application: All persons interested in submitting a YIA application MUST first submit a Pre-Application. Pre-Applications will be reviewed by the Foundations’ Research Advisory Board (RAB).  Based on this review, you will be notified whether or not you are invited to submit a Full Application.  

To submit, please email completed pre-application to Ms. Min Wong.

2.    YIA Full Application: Only those who receive an invitation from CTF may submit a YIA Full Application.
If you do not submit a Pre-Application you cannot submit of a Full Application. Unsolicited Full Applications will be returned without review.

APPLICATION PROCESS DEADLINES:

January 27, 2012: Pre-Application Due. Please email completed pre-application to Ms. Min Wong.

February 24, 2012: Invite to submit Full Applications will sent via email

April 2, 2012: Full Application Due

Questions?? Please contact This e-mail address is being protected from spambots. You need JavaScript enabled to view it    

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Announcing Our 2011 Young Investigator Award Recipients

 The Children’s Tumor Foundation is delighted to announce the funding of SIX Young Investigator Awardees for the 2011 round. The recipients include three postdoctoral awardees and three graduate students; three focused on aspects of NF1 including tumors, bone dysplasia and learning disabilities; and three focused on NF2 or schwannomatosis. Four awardees are US-based and two are international. Details of the Awards, as well as Past Awardees are listed below.  

Young Investigator Awards provide the recipient with two years of salary support plus a $5,000 travel stipend to attend the NF Conference and other meetings. The 2011 Awardees represent an investment for CTF of just under $500,000.  

2011 PRE-DOCTORAL AWARDEES

YIA Template Forms

• YIA Progress Report Template
• YIA Expenditure Report Template
• YIA Travel Allowance Request Form

 2010 Recipients | 2009 Recipients | Past Recipients

2010 Young Investigator Awardees

POSTDOCTORAL AWARDEES

	Nicolas-Xavier Bonne, MD, House Ear Institute Analysis of tumor development after stereotactic radiosurgery in NF2 mouse models Use of radiosurgery and radiotherapy for NF2 management is highly controversial, with some physicians utilizing this and others not. There are differences of opinion as to whether observation, microsurgery or radiosurgery is more effective in hearing preservation, and whether this treatment may induce malignancy.  Dr. Bonne will use NF2 mouse models to endeavor to address these important questions, treating the mice with radiotherapy and evaluating the short- and long-term outcomes.
	Thomas DeRaedt, Ph.D., Harvard Medical School/Brigham and Women’s Hospital Combination Therapy for NF1 associated MPNST Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are a rare but devastating and lethal tumor that can develop in NF1 from plexiform neurofibromas. Building on the established finding that Rapamycin will have some effect on inhibiting NF1 tumor growth, Dr. DeRaedt uses mouse models of MPNSTs to test new combination drug treatment approaches for these difficult to manage tumors.
	Jean Gouzi, Ph.D., Harvard Medical School/ Massachusetts General Hospital Identification of novel molecular modifiers of NF1 learning disabilities in Drosophila Dr. Gouzi takes new approaches to understanding NF1-related learning disabilities by using the fruit fly to look at novel genetic regions that have been identified and may have a role in regulating NF1 gene function.  Fruit flies  make terrific models for studying learning behavior as have well established genetic homology (parallels) with humans allowing for the translation of results from flies to humans; and they can be assigned tasks and responses measured. As a result, by using flies with different genetic mutations or after they have received a drug treatment, new genes may be identified that are contributing to the learning defect and therefore represent future candidate drug targets.
	Azar Omrani, Ph.D., Erasmus Medical Center, The Netherlands Role of the neuron-specific isoform of neurofibromin in learning and synaptic plasticity Dr. Omrani seeks to better understand learning disabilities in NF1 with an eye on developing clinical interventions (the primary focus of the laboratory in which she will be doing this research). She will focus on a special modified version of NF1 protein which is generated by a specific NF1 genetic element called exon9a and which plays an important role in regulating neuronal function in the normal brain. Mice lacking exon9a have learning deficits and Dr. Omrani will focus on whether understanding this can be harnessed to develop treatments for persons with NF1 learning disabilities.

PRE-DOCTORAL AWARDEES

Maryam Jahanshahi, Mount Sinai School of Medicine, New York Identifying and characterizing novel effectors of Merlin that have a role in NF2 cell growth This study will utilize fly models of NF2 to examine the potential roles of new NF2 gene regulators in causing cell growth, with the goal of identifying new drug targets for NF2 treatment. Of particular interest Ms. Jahanshahi will endeavor to identify genes that are expressed at different levels in different individuals and may help explain why NF2 can affect persons with different levels of severity.

Sherry Phillips, Indiana University Neurofibromin’s role in sensory neuronal sensitization Ms. Phillips focuses on an important but understudied aspect of NF1, which is to understand the fundamental causes of why individuals with NF1 can experience enhanced pain. This study focuses on cell signaling elements adenylyl cyclase (AC) and cAMP, and the underpinnings of their role in NF1 pain. The goal is to determine why there are enhanced pain sensations in NF1 and help elucidate future clinical management approaches.

2009 Young Investigator Awardees:
From Schwannomatosis Genes to New NF1 and NF2 Drug Therapies

POSTDOCTORAL AWARDEES

Jody Fromm, Ph.D., Harvard Medical School/Brigham and Women’s Hospital
To determine the therapeutic effects of combined sunitinib and rapamycin treatment on MPNSTs in a genetically engineered mouse model
The primary clinical feature of NF1 is the development of benign tumors in the nerve tissue, classified as either dermal or plexiform.  Whereas dermal tumors develop progressively throughout life and are relatively small, plexiform tumors can form before birth, can grow to be quite large, and can develop into malignant peripheral nerve sheath tumors (MPNSTs).  Those tumors that can be surgically removed unfortunately often regrow, and despite radiation and, in some cases chemotherapy, inoperable MPNSTs progress rapidly and are typically lethal; therefore identifying an effective alternative treatment for these tumors is critical.  Previous studies carried out by Dr. Fromm’s lab revealed that human MPNST cells are extremely sensitive to mTOR inhibitors, such as rapamycin, which immediately halts tumor growth and prolongs the survival of a genetically engineered MPNST mouse model.  However, as would be predicted from studies with other targeted therapies, they also found that the tumors in their mouse model ultimately become resistant to mTOR inhibitors.  The present study will therefore take two distinct approaches to develop more effective combination therapies.  First, Dr. Fromm proposes to investigate the mechanism by which tumors re-establish their blood vessel network after treatment with rapamycin and assess the therapeutic effects of anti-angiogenic agents in combination with rapamycin in vivo. Second, she will evaluate the mechanisms of rapamycin resistance by compiling gene expression profiles of pro-angiogenic factors in sensitive and resistant tumors.  The findings from this study will hopefully develop into effective therapies for NF1 patients.

Wei Li, Ph.D., Memorial Sloan-Kettering Cancer Center
Role of Merlin in the nucleus during tumor suppression
NF2 is a disorder characterized by the growth of tumors in the nervous system, and symptoms often manifest at an early age.  Most of the tumors originate from Schwann cells, which surround and insulate nerve cells, but while local surgery and radiation are the primary treatments, they carry the risk of damaging the central nervous system.  Determining the molecular pathology of this disorder would therefore help in the discovery of novel therapeutic approaches at the molecular level.  This study seeks to understand how the absence of the Merlin protein, produced by the Neurofibromatosis type 2 (Nf2) gene, induces Schwann cells to overproliferate and to give rise to tumors.  Although the exact molecular function of Merlin remains unknown, it is involved in controlling cell growth and division, cell movement, cell shape, and communication between cells.  Additionally, Dr. Li’s laboratory recently discovered that Merlin interacts with and inhibits a novel E3 ubiquitin ligase, an enzyme found in cell nuclei. Members of this ligase family usually regulate protein functions and degradation, so our studies indicate that inhibition of this ligase is important to Merlin-mediated growth inhibition and tumor suppression. The goal of this research is to further study the role of Merlin in the nucleus during tumor suppression so as to provide a new horizon for understanding the mechanism by which Merlin suppresses tumorigenesis and to contribute to the development of new and more effective therapies for NF2.

Arkadiusz Piotrowski, Ph.D., University of Alabama at Birmingham
DNA methylation and subchromosomal structural rearrangements as contributing causal factors in schwannomatosis
Point mutations, or single base pair changes in DNA, affecting the INI1 gene have recently been implicated as causal factors of Schwannomatosis; however, most phenotypic manifestations of this disorder have not been associated with specific point mutations in INI1. Furthermore, complete inactivation of INI1 is either lethal or leads to diseases different from Schwannomatosis.  Structural rearrangements, i.e. losses or multiplications of segments in the human genome, are possible yet unexplored components that may decrease or increase activity of the INI1 gene and other genomic regions implicated in Schwannomatosis. Another factor that may lead to similar effects is DNA methylation. Methylation is an epigenetic alteration, which means modification of DNA without actual change in DNA sequence. Both structural rearrangements and DNA methylation may affect activity of genes in a subtle way that is required in the development of the disease. In order to address this issue, Dr. Piotrowski has designed experimental assays based on custom microarrays and complementary techniques, which his lab successfully validated in previous studies. These tools have been further tailored specifically to suit the analysis of Schwannomatosis-associated genes and genomic regions on chromosome 22. Finally, using genome-wide array-CGH, they will test the alternative hypothesis that there exist regions outside of chromosome 22 in the human genome that harbor deletions and/or duplications of genetic material that may contribute to the pathogenesis of Schwannomatosis. In the current project, Dr. Piotrowski plans to test the hypothesis of the involvement of DNA methylation and small structural rearrangements as contributing causal factors in Schwannomatosis. 

Chunling Yi, Ph.D., The Wistar Institute
Development of novel targets and therapeutics for the treatment of NF2
NF2 is caused by mutations of the Nf2 gene, which encodes a protein called Merlin.  Merlin negatively regulates signaling by Rac/Ras, small proteins that control a wide array of cellular processes, including cell growth, by inhibiting Pak, a downstream signaling protein in the Rac/Ras pathway.  Dr. Yi’s lab has recently shown that Pak is abnormally activated in schwannoma samples from NF2 patients and that Pak serves as a viable therapeutic target for NF2.  In a collaboration effort, they have successfully developed highly specific and potent small-molecule Pak inhibitors. The first part of this proposal is aimed at further improving the specificity and potency of the Pak inhibitors and testing them in cellular and animal models of NF2. Should these inhibitors prove to alleviate tumor development in animal models, it would provide a novel therapeutic modality for NF2 patients. While Pak inhibitors show great promise, available evidence indicates that Merlin may target additional proteins within the cell. To identify new Merlin targets, preliminary studies were undertaken and resulted in the purification of a novel protein complex that is comprised of Merlin and associated proteins angiomotin, patj, and pals1. This preliminary study suggests that angiomotin also functions as a modulator of Rac signaling. The second half of this proposal will be devoted to the further investigation of the role of Merlin-angiomotin complex in cell signaling and schwannoma development. Taken together, these studies should provide novel compounds for development as therapeutics and should significantly further understanding regarding the disease mechanism of NF2. 

PRE-DOCTORAL AWARDEES

Ana Oliveira, Duke University Medical Center
The role of neurofibromin in spine morphology and plasticity
Learning disabilities are common in children with Neurofibromatosis type 1 (NF1), and these severely reduce the quality of life of many patients; however, the pathogenic process for NF1-associated learning disabilities has not been fully understood.  The goal of this study, therefore, is to understand the role of Neurofibromin, the protein encoded by the Nf1 gene, in synaptic plasticity, the cellular basis of learning and memory.  Neurofibromin regulates a protein called Ras, which is known for its role in initiating cell proliferation, but in NF1, Neurofibromin is mutated and cannot perform its normal function.  The learning deficits in an animal model of NF1 are caused by the hyper-activation of Ras.  This study will focus specifically on the role of Neurofibromin on Ras signaling in dendritic spines, protrusions from a neuron’s dendrites that receive input and transmit signals to the cell body of the neuron. Ras activation induced by NMDA receptors in dendritic spines is required for many forms of synaptic plasticity including long-term potentiation (LTP) and the formation of synapses. Because neurons communicate via synapses, and because it is believed that memory is stored in these synapses, LTP, which signifies enduring improvement in interneural communication, is considered to be a major mechanism of learning. Given that Neurofibromin is accumulated in dendritic spines and interacts with NMDA receptors, our central hypothesis is that Neurofibromin is important for the regulation of the NMDA receptor–Ras pathway in dendritic spines, and can thereby regulate the morphological and functional plasticity of dendritic spines. This project is expected to elucidate the molecular mechanisms of impaired synaptic plasticity and learning due to reduced level of Neurofibromin, and hopefully to facilitate the development of new therapeutics for ameliorating the learning disability of NF1 patients.