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NIH invites proposals for 2012 NIH Director's Pioneer Awards and New Innovator Awards for innovative approaches to major challenges in biomedical or behavioral research. 

• Pioneer Awards:  
  • Up to $2.5 million in direct costs over 5 years
  • Open to scientists at any career stage. 
•  New Innovator Awards: 
  • Up to $1.5 million in direct costs over 5 years
  • For early career stage investigators (ESI), defined as those who have not received an NIH R01 or similar grant and are within 10 years of completing their terminal research degree or medical residency.   

NIH expects to make at least 7 Pioneer Awards and at least 33 New Innovator Awards in summer 2012.  The deadline for submitting Pioneer Award applications is October 7, 2011. See the instructions in the Funding Opportunity Announcement RFA-RM-11-004.  
The deadline for submitting New Innovator Award applications is October 14, 2011. See the instructions in the Funding Opportunity Announcement RFA-RM-11-005.  

Schwannomatosis is the least well understood form of neurofibromatosis and also the rarest, affecting an estimated 1:40,000 persons. It causes tumors to grow on peripheral nerves throughout the body and severe, untreatable pain.  In 2007 the first candidate schwannomatosis gene was reported but there is much to learn and understand on the path to developing treatments. Since that time CTF has been at the forefront of leading schwannomatosis progress investing over $600,000 in projects including  genetics, animal model development, preclinical drug testing and establishing a Schwannomatosis International Database.  As well as funding research, CTF has accelerated progress and collaboration in this area by hosting a series of expert consensus meetings, the most recent in June 2011 from which a state-of-the-field report is being developed for publication.

As an outcome of the June consensus meeting, CTF announces a request for Applications for Schwannomatosis Awards up to $75,000. Funding may be requested for ANY research in any area of relevance to advancing schwannomatosis; areas of emaphasis are Genetics, Cell Biology & Translational Research; and Clinical Research. Applications must be received by Monday October 3^rd, 2011. For more information visit http://www.ctf.org/For-Scientists/schwannomatosis-awards.html

The Children’s Tumor Foundation is delighted to announce the funding of SIX Young Investigator Awardees from application received for our 2011 program. 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 NF2or schwannomatosis. Four awardees are US-based and two are international.    The 2011 Awardees represent an investment for CTF of around $500,000.
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.
2011 YIA recipients are as follows:
Miriam Smith, Ph.D., University of Manchester, United Kingdom. Project: Identification of novel genes predisposing to schwannomas and meningiomas by exome

Jonathan Payne, Ph.D., University of Sydney, Australia. Project: The Neural Basis and Treatment of Reading Disability in Children with NF1

Jianzhong Yu, Ph.D., Johns Hopkins University. Project: Molecular genetic characterization of the Merlin tumor suppressor protein complex

Alejandra Petrilli Guinart, University of Central Florida. Project: LIM kinase - a potential therapeutic target for NF2

Steven Rhodes, Indiana University School of Medicine. Project: Targeting the hematopoietic bone microenvironment in the treatment of NF1 pseudarthrosis

Adrienne Watson, University of Minnesota. Project: Understanding the Role of Wnt Signaling in Malignant Peripheral Nerve Sheath Tumors

For more information on these projects and past YIA recipients please visit:
http://www.ctf.org/For-Scientists/young-investigator-awards.html

This weekend the Children's Tumor Foundation participated with around 100 researchers,  clinicians and foundation representatives in the Second International Rasopathies Network Conference in Chicago.  The Rasopathies Network was conceived through a collaboration between physicians focused on, and families affected by, 'Rasopathies' - or rare diseases that affect signaling in the Ras pathway. Rasopathies include neurofibromatosis, Noonan's Syndrome, Costello Syndrome, Cardio-Facio-Cutaneous (CFC) Syndrome and Leopard Syndrome. These rare conditions share many common features, including learning disabilities, and skin and bone manifestations, with impact on quality and span of life. The goal of the Rasopathies Network is to drive collaboration between scientists working on the different rare diseases to accelerate research. The  2011 Rasopathies Network Conference was organized to occur at the end of a six-day schedule of family conferences and clinics for Noonan's, Costello and CFC families, which made for a busy and informative time.  Overall neurofibromatosis research has made significant advances compared to the other rare diseases and we  got some good words for our NF Clinic Network and preclinical programs.  But we can definitely learn from some of the approaches the other groups are taking, for example to develop patient health records, and to improve clinical care guidelines. As candidate drugs emerge, it is likely that they will have applicability across many of these rasopathies therefore ongoing communication is vital as the research moves forward.  At the close of the weekend CTF and the NF Network (formerly NF Inc) jointly participated in a small NF Symposium for local attendees where Alcino Silva (UCLA) and Maria Acosta (Children's National)  gave updates on learning disabilities research and trials; I presented some highlights from the recent 2011 NF Conference;  and Kim Bischoff (NF Network) gave a presentation on the importance of advocacy for NGF research funding. 
We looks forward to the 2013 meeting of this group, and to future collaborations with the Rasopathies Network and to both sharing our knowledge and learning a lot!

This weekend the Children's Tumor Foundation participated with around 100 researchers,  clinicians and foundation representatives in the Second International Rasopathies Network Conference in Chicago.  The Rasopathies Network was conceived through a collaboration between physicians focused on, and families affected by, 'Rasopathies' - or rare diseases that affect signaling in the Ras pathway. Rasopathies include neurofibromatosis, Noonan's Syndrome, Costello Syndrome, Cardio-Facio-Cutaneous (CFC) Syndrome and Leopard Syndrome. These rare conditions share many common features, including learning disabilities, and skin and bone manifestations, with impact on quality and span of life. The goal of the Rasopathies Network is to drive collaboration between scientists working on the different rare diseases to accelerate research. The  2011 Rasopathies Network Conference was organized to occur at the end of a six-day schedule of family conferences and clinics for Noonan's, Costello and CFC families, which made for a busy and informative time.  Overall neurofibromatosis research has made significant advances compared to the other rare diseases and we  got some good words for our NF Clinic Network and preclinical programs.  But we can definitely learn from some of the approaches the other groups are taking, for example to develop patient health records, and to improve clinical care guidelines. As candidate drugs emerge, it is likely that they will have applicability across many of these rasopathies therefore ongoing communication is vital as the research moves forward.  At the close of the weekend CTF and the NF Network (formerly NF Inc) jointly participated in a small NF Symposium for local attendees where Alcino Silva (UCLA) and Maria Acosta (Children's National)  gave updates on learning disabilities research and trials; I presented some highlights from the recent 2011 NF Conference;  and Kim Bischoff (NF Network) gave a presentation on the importance of advocacy for NGF research funding. 
We looks forward to the 2013 meeting of this group, and to future collaborations with the Rasopathies Network and to both sharing our knowledge and learning a lot!
 

A team of researchers has identified the genetic mutation that causes Proteus syndrome, a rare disorder in which tissue and bone grows massively out of proportion. Only 300 people  worldwide are believed to be affected by this very rare condition.   The report appears in the July 27, 2011, early online edition of the New England Journal of Medicine.

It has long been speculated that the Elephant Man had Proteus Syndrome. It has been speculated too that in addition to Proteus Syndrome he may also have had NF1 gene mutations, but this has never been demonstrated conclusively. It is known that his clinical appearance would match a severe form of Proteus Syndorme.
The new discovery has broad implications for potential drug therapies and will also potentially inform neurofibromatosis research as well as cancer.  The team was led by researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health.
 
The mutated gene associated with Proteus Syndrome is AKT1, and is an oncogene i.e. it can promote the uncontrolled cell growth associated with cancer and as seen in Proteus Syndrome. Interestingly AKT1 has also been under consideration as a drug target for neurofibromatosis since it is on the same cellular signaling cascade. 

On June 27th-28th the Children's Tumor Foundation is convening a Schwannomatosis Workshop (think tank) in Los Angeles. International expert researchers and clinicians will review the most recent findings in schwannomatosis research and clinical care, share progress and chart the future path to improving care and finding effective treatments for schwannomatosis.  I look forward to reporting the outcome of  the next 2 days of meetings. Below is a preview to set the stage.

I'll be staying in LA for the remainder of the week to attend the Acoustic Neuroma 2011 Meeting which includes a lot of NF2-relevant presentations, and will be reporting on that later in the week too. 
Schwannomatosis is the most rare form of neurofibromatosis affecting an estimated 1:40,000 persons. It causes the growth of multiple peripheral nerve tunors called schwannomas, and in addition it causes chronic, severe and unmanageable pain. There are no treatments for this. For a long time schwannomatosis was not well understood and in fact the first guidelines for its clinical diagnosis were not published until 2005.  A breakthrough came in 2007 with the publication of the first candidate schwannomatosis gene, INI-1/SmarcB1/Snf5. This gene has emerged to be a key player in schwannomatosis but interestingly there may also be involvement of the NF2 gene in the onset and progression of schwannomatosis. Schwannomatosis research faces added challenges as there are so few patients, so to accelerate progress CTF has brought this community of researchers and clinicians together since 2007 for a series of think tanks and they have shared and collaborated extensively with each other. CTF has been a major force in advancing schwannomatosis research in the past 4 years since the candidate gene was identified. In addition to hosting the think tanks, CTF has invested more than $700,000 in schwannomatosis research in this period. Projects we have funded include the creation of a schwannomatosis patient database now up and running;  the creation of the first 2 mouse models of schwannomatosis, both of which are now  being utilized for preclinical drug testing to reduce tumor growth and pain; and further genetics studies. Look for updates from the schwannomatosis think tank in the next day or so!

Today we feature a Guest Blog featuring a report from the 2011 NF Conference from Dr. Fawn Leigh, a pediatric neurologist at the Massachusetts General and Harvard Medical School. Dr. Leigh presented the following project at the Conference, and is looking for further research collaborators, as well as any persons with NF1 who would be willing to participate and donate tissue, whether or not they are currently under care of an NF clinic.

At the 2011 NF Conference in Jackson Hole I gave a talk highlighting my findings from a pilot study to identify modifier genes that may inform the identification of potential drug targets and treatments in NF1. The study focused on a search for modifier genes of cutaneous (dermal) neurofibroma tumor burden in NF1. This was done through a genome-wide association study (GWAS).  300 NF1 subjects identified as having either the largest or least 15% of cutaneous tumor burden were genotyped using the Affymetrix GeneChip 6.0 platform. This provided 909, 622 single nucleotide polymorphism (SNP) markers and >946,000 probes for copy number variants (CNV).  The analysis revealed potential hits (P values of 10-4 to 10-7) with multiple SNPs at each of several regions of the genome. Each of these segments constitutes a candidate region that merits genotyping in an additional cohort of extreme subjects to either confirm or refute its modifier status, which is ongoing.  The CNV analysis is in progress. The current GWAS study is a collaboration of six centers across the world.  Five new centers recently joined this project. 

For researcher or patients seeking additional information about participating in this study, please contact:  Stephen Ranney (Clinical Research Coordinator)

Email: administrator@cnfad.org               Office: 617-724-2365

The 2011 NF Conference concluded today with a packed agenda of exciting talks, kicking off with some clinical trial updates. Kent Robertson (Indiana University) reported on a trial of Gleevec (Imatinib) in NF1 patients with clinically significant plexiform neurofibromas, age 3-65.  Individuals received drug for 6 months, and if they received benefit they were given the opportunity to stay on the drug.  60% of patients showed a response in one or more of their plexiforms, and 40% of those patients showed an improvement in ther symptoms such as issues with bladder control and airway function.  Dr. Dusica Babovic-Vuskanovic (Mayo Clinic) reported on the concluding Phase II trial assessing the response of NF1 plexiform neurofibromas to Cediranib (AZD2171), a VEGF-targeted agent. 26 patients, 18 years and older participated in the trial and received drug for periods of 18-41 months. 4 patients showed continuous and sustained tumor shrinkage. In addition the trial assessed changes in pain via a quality of life survey, and found that pain levels decreased over the period of drug treatment.  Kimberly Jett (University of Alberta) reported on her study showing that NF1 patients can have reduced levels of Vitamin D in the serum, and that treatment with Vitamin D can increase bone mineral density in these individuals, potentially helping to allay future bone problems.

Sarah Burns (Ohio State University) described research using the PI3K/AKT targeted drugs AR42 and AR12. These drugs are in development at Arno Therapeutics and in clinical trials for a number of cancers. Previous CTF-funded preclinical research by this group has shown that these drugs are candidate therapies for NF2 vestibular schwannomas.   This presentation reported potential efficacy of these drugs in halting or slowing the growth of benign meningiomas.  David Ingram (Indiana University) is focused on the area of vascular disease in NF1. Persons with NF1 are at increased risk of vascular disease. Dr. Ingram has developed mouse models that develop the features of vascular disease, such as infiltration of macrophages. These mice will be valuable study models for understanding the biology and testing drug interventions. Looking ahead, the goal is to be able to identify early subclinical vascular disease so it can be treated before it progresses.

112 posters were presented at this year’s NF Conference, and these were judged by small committees of researchers and clinicians to determine Best Poster in Basic Research and Clinical Research categories.  Consideration was given to merit, originality and depth of data. The winners were: Best Poster – Basic Research: Juliana Ferreira de Souza (Federal University of Mina Gerais, Brazil) – “Aerobic Capacity Is Reduced In Patients With NF1: A Preliminary Report”; and Best Poster-Clinical Research:  Melissa Hinman (Case Western Reserve University) - “The Biological Role of the Regulation of NF1 Exon 23a alternative splicing”.

The 2011 NF Conference kicked off this weekend with some interesting and exciting presentations.  On Saturday, Dr. Filippo Giancotti (MSKCC) provided an update on his novel research first reported in 2010 that described for the first time a role for NF2 merlin protein in the cell's nucleus. Dr. Giancotti has continued to unravel the signaling activities of merlin in the nucleus, and interestingly also showed that in sections of human meningioma tissue,  merlin protein is not present in the nucleus. This would provide support for Dr. Giancotti's unique idea that merlin controls normal cell division and that lack of its nuclear function might be a factor in promoting NF2 tumor growth.  

On Sunday, Dr. Alison Lloyd (University College London) chaired a session on the biology of peripheral nerve development and what we can learn from this and apply to understanding disease and specifically NF1. Dr. Lloyd herself presented some really interesting findings  in mice where Erk signaling was disrupted in peripheral nerves by genetic mutation. The result is that the nerves undergo an inflammatory response, the blood nerve barrier function is lost and in short the nerve looks to all intents and purposes like they have been physically injured. Because Erk signaling is also disrupted in NF1 neurofibromas, this research opens the door to comparing this model of nerve injury to disease progression in NF1 tumors to see what one can teach the other. In the same session Dr. Luis Parada (University of Texas Southwestern) described an ongoing study in which he is screening pairs of drugs from a large compound library on malignant peripheral nerve sheath tumor cells.  The study is beginning to identify potentially novel drug targets for the treatment of these NF1 tumors. Dr. David Largaespada (University of Minnesota) closed out the session with a report o his CTF-funded research focused on better understanding the exact nature of gene mutations that lead to neurofibromas, and how this can help us identify new drug targets. 

On Sunday evening, Dr. Jaishri Blakeley  (Johns Hopkins University) provided an update of her CTF-funded clinical trial of Lapatinib in vestibular schwannomas. This ‘Phase Zero’ trial is focused on giving patients drug prior to vestibular schwannoma surgery so that the excised tumor can be studied to see if the drug reached the target. This type of study provides a rapid preliminary evaluation to determine if a full scale Phase II trial is worthwhile. So far there is not compelling evidence that Lapatinib is effective but the trial is not yet complete so we look forward to seeing the final data.  Dr. Fabio Nunes (Harvard) did a retrospective review of NF2 patients treated with bevacizumab (Avastin) for their vestibular schwannomas, to see if there were also additional effects on meningiomas. While there were modest effects of the drug in some tumors within some patients, this was not strongly compelling suggesting bevacizumab is not likely to be a promising therapeutic for meningioma.  CTF Young Investigator Irma Rangel-Alarcon (UCSF) proposed a function for the protein encoded by the Spred-1 (Legius Syndrome) gene suggesting it has close interactions with the NF1 protein (neurofibromin) in the cell. This study could potentially help unravel why there is overlap in the clinical presentation of NF1 and Legius Syndrome.  

Closing out Sunday evening Amanda Bergner (Johns Hopkins) provided an update of the CTF-funded Schwannomatosis Database which now has 14 US and international sites participating, has enrolled 27 patients and aims to have 200 patients registered by the end of 2011.