Frequently asked questions
Neurofibromatosis & NTAP
NTAP stands for the Neurofibromatosis Therapeutic Acceleration Program. NTAP is a research enterprise focused on accelerating the development of therapies for neurofibromatosis type 1 (NF1). Our research focuses on the two most common tumors that appear in patients with NF1: cutaneous and plexiform neurofibromas. NTAP was founded in 2012 at Johns Hopkins University School of Medicine and is open to working with researchers from academic institutions, government and industry around the world.
Neurofibromatosis is a genetic disorder that causes tumors to form throughout the body. There are three types of neurofibromatosis, and at NTAP we focus on neurofibromatosis type 1 NF1.
Neurofibromatosis type 1 is a genetic condition of the nervous system. The prevalence of NF1 is estimated at between 1 in 2,500 to 1 in 3,500 in individuals. NF1 causes tumors to grow on the nerves (neurofibromas). It can result in altered organ function and increases the risk for several cancers.
An alteration in one gene line allele of NF1 is sufficient to result in the clinical syndrome of NF1. However, tumor formation requires loss of function in the second allele. The fact that biallelic loss of NF1 is required for tumor formation defines NF1 as a tumor suppressor gene. Manifestations of NF1 include skin markings (café-au-lait spots and freckling), Lische nodules in the eye, bone or vascular malformations, learning and cognitive difficulties, and commonly tumors of the nerves throughout the body called neurofibromas.
There are three types of neurofibromatosis (NF): NF1, NF2 and schwannomatosis. They are caused by different genes, located on different chromosomes. Neurofibromatosis type 1 (NF1) results from an inherited or spontaneous alterations in the neurofibromin gene (NF1).
Cutaneous neurofibromas (cNFs) are the most common skin tumor in people with NF1. Cutaneous neurofibromas affect more than 95% of people with NF1. The number of cutaneous neurofibromas varies, and can count in the hundreds or even thousands throughout the body in a given individual. These tumors cause disfigurement, pain and itching and the lack of effective therapies are a major unmet need.
Plexiform neurofibromas (pNFs) are tumors that form in individual or multiple deep nerves. Up to 50% of people with NF1 develop plexiform neurofibromas. These tumors are histologically benign, but can cause major neurologic and organ dysfunction. Additionally, up to 15% of pNF tumors transform into an aggressive form of cancer known as malignant peripheral nerve sheath tumor (MPNST). Selumetinib is the first FDA-approved oral drug for pNF in children with NF1.
NTAP is solely dedicated to scientific research and bringing new leaders into the field. If you are looking for patient support or advocacy, please reach out to our partners at the Children’s Tumor Foundation who do an outstanding job at these two activities.
Applying for a Grant
1. In general
Currently, NTAP is strictly focused on the peripheral nerve tumors of NF1: Cutaneous, Plexiform and Atypical or ANNUBP.
NTAP has three programs: 1. Open Proposals 2. Francis S. Collins Scholars Program 3. Solicited Proposals, which are topic-specific requests for applications (RFAs).
The Open Proposal program is open all year and applications for novel research ideas are accepted on a rolling basis. Applications must focus on cutaneous, plexiform or atypical neurofibroma. The Francis S. Collins Scholars Program has an annual application deadline in December. NTAP announces Request for Applications (RFA) on specific topics periodically.
Grant applications should be submitted through ProposalCentral (PC).
The lead Primary Investigator (PI) can upload biosketches and other support materials through Proposal Central. Go to the Key Personnel/Collaborators page and enter the PI’s email address and role on the project. You will then be able to upload sketches. If you have trouble entering materials, contact info@n-tap.org.
A full grant application to NTAP requires signatures. After validating your application, you and your institute signing official may do the electronic signature.
Yes. Indirect costs are allowed up to 10% of direct costs, and for some programs, this number may be higher.
The first review is completed within two weeks. Peer review is generally completed within one month. For applications that are reviewed favorably and are eligible to proceed to funding, there is typically a process of discussion and revision. Proceeding to contracting depends on the length of this process. It generally takes less than 90 days from receipt of proposal to final decision.
Submitted proposals are reviewed internally by NTAP leadership to determine if they are in scope with NTAP's mission and are of appropriate caliber to convene a peer review panel. Applications selected for progression to peer review are reviewed by at least three peer reviewers, including NF and subject matter experts.
The review criteria vary and depend on the initiative. Detailed information for specific initiatives is provided on the announcement and on ProposalCentral.
NTAP uses a milestone and deliverable-based funding model. When a proposal is selected for funding, the investigator is asked to finalize a milestone and deliverable schedule in collaboration with NTAP leadership. Each milestone has a budget amount associated with it. NTAP makes payment to the investigator or institution based on evidence that the milestone has been completed.
A no cost extension (NCE) request may be submitted by the PI with a research plan and budget justification during the NCE period. NTAP leadership will review the NCE request and work with the investigator to create a plan.
No. Each NTAP-awarded project stands alone.
Applying for a Grant
2. The Open Proposal Program
Open Proposals support independent research projects that accelerate the development of effective treatments for NF1. This includes plexiform neurofibromas (pNFs), cutaneous neurofibromas (cNFs) and atypical neurofibromas (aNF). The purpose of the Open Proposal program is to broaden and diversify the strategies applied to NF1 research. Applications may be for small, highly- focused projects or complex program project grants.
Grant applications submitted under the Open Proposal program must focus on peripheral nerve tumors of NF1. The proposal must be focused on NF1 plexiform, cutaneous or atypical neurofibromas. There is no limitation on the funding amount, project duration, or complexity of the study, as long as these are expressly justified as important to the success of the project. All investigators are encouraged to apply and have an equal opportunity to win grant funding regardless of geography, institution or background.
NTAP’s Open Proposal program is open to investigators without limitation. Investigators from any part of the world and from any scientific background are eligible for NTAP awards.
Proposals must be no longer than five pages, single-spaced in typeface no smaller than Arial 11-point and 0.5” margins. This limit does not include a bibliography. The bibliography and proposed Milestones/Deliverables are two additional documents with no page limit.
Unlike NIH grant applications, NTAP does not require a separate vertebrate animal or human subjects section. We will request a copy of an approved IACUC/IRB for awarded proposals when proceeding to contracting. However, investigators must describe and justify animal or human study details in the proposal including species, strain name/number, source, sex, age, number/group.
There is no specific requirement for the number of support letters. Generally, your application may include letters of support from your institution such as the Director, or Department Chair (if the PI is a junior investigator), along with key personnel, collaborators, and other significant contributors. Applicants are encouraged to send any letters they believe will support your proposed research and proposal.
If the revision involves only the updating of attachments, you may do so without un-submitting the application. To upload a new file, send it to NTAP directly by email to info@n-tap.org.
There is no limit for direct and total budget but the direct costs should be appropriate and well justified to perform the proposed research.
Applying for a Grant
3. The Francis S. Collins Scholars (FCS) Program
The Francis S. Collins Scholars Program in Neurofibromatosis Clinical and Translational Research is designed to build a community of exceptional clinician-scientists who will lead NF1 research and clinical care.
The Francis Collins Scholars (FCS) program is open to anyone who has a health professional degree that permits patient care and is willing to commit a minimum of 75% of their professional effort to NF1. Program scholars must be willing to participate for a minimum of two years and a maximum of three years. Applicants should be in the last stages of post-doctoral training or a junior faculty member within seven years of the first faculty appointment. Detailed eligibility requirements can be found on the Francis Collins Scholars page. If you have questions about the program, please email info@n-tap.org.
The documents required for application to the Francis Collins Scholars application program include:
1. professional history (1 page maximum)
2. career development plan (4 page maximum)
3. research project description (10 page maximum)
4. NIH formatted biosketch
5. mentorship plan (3 page maximum)
6. budget and budget justification
7. letters of support (a minimum of three letters of support are required).
Additional details are available in the program guidelines.
The program includes salary support based on the NIH salary cap. In addition, the following funds are available:
1. Mentor stipend ($10,000 per year)
2. Research costs (up to $20,000 per year)
3. Travel costs (up to $10,000 per year)
4. Education expenses (up to $10,000 per year)
The Primary Investigator's salary and mentor stipend are fixed costs. Research, travel and education expenses are reimbursable costs.
Yes. Indirect costs are permitted up to a maximum of 10% of direct costs. However, no indirect costs are permitted on patient care-associated costs.
All applications undergo an initial review by NTAP staff. If the application is complete, it is forwarded to a pre-selected review panel for detailed review. Reviewers are senior medical and scientific leaders recruited across disciplines pertinent to NF1 research, who have expertise in clinical or translational science.
Francis Collins Scholar application reviewers will evaluate each application on the following criteria:
1. applicant’s research history
2. career development plan
3. merit and feasibility of research proposal
4. mentorship plan
5. budget and budget justification
Johns Hopkins NF1 Biospecimen repository
The John Hopkins NF1 biospecimen repository program is one of the most comprehensively annotated biorepositories of tissue and blood fractions in the world for use in NF1 research. The goal of the program is to increase availability of these tissues to the NF1 research community through scientific resource and data sharing.
The repository has collected NF1-associated tumors including cutaneous neurofibroma, diffuse infiltrating neurofibroma, plexiform neurofibroma, atypical neurofibroma, and malignant peripheral nerve sheath tumors (MPNST), and blood fractions from patients with NF1. The bank also collects and banks any malignancy from a patient with NF1 including breast cancer, GIST, and brain cancer. A current inventory of available specimens can be found here.
The following specimens are available: frozen tissue, patient derived xenografts, cell lines, and blood normal. The bank contains clinical information and genomic data such as RNAseq and whole exome sequencing (WES). The genomic data can be obtained through Synapse/NF Data Portal upon request via this link.
Investigators interested in requesting specimens for their research can complete a specimen request form. The details on how to apply as well as the application form can be found here. Each request will be reviewed by an internal scientific review committee and the Johns Hopkins University human Institutional Review Board (IRB). Investigators will be notified of a decision within approximately two months.
The link to the Johns Hopkins NF1 biospecimen repository is here.
ATCC cell line reimbursement
The reimbursement program was initiated by NTAP in 2018 to promote plexiform neurofibroma research and to foster collaboration.
NTAP’s current cell line reimbursement program is for the immortalized human plexiform neurofibroma cells and Schwann cells of ATCC. i) hTERT ipNF05.5 (mixed clones) (CRL-3387), ii) hTERT ipNF 05.5 (single clone) (CRL-3388), iii) hTERT ipNF95.6 (CRL-3389), iv) hTERT ipNF95.11b C (CRL-3390), v) hTERT ipNF95.11c (CRL-3391), and vi) hTERT ipNF02.3λ (CRL-3392).
Anyone who uses the ordered ATCC’s immortalized human plexiform neurofibroma cells for NF1-related research is eligible. The basic premise is that reimbursement is supported when research efforts are intended to advance NF1-related discovery and therapeutics.
Yes.
Yes. To be eligible, requests for reimbursement need to be received by NTAP within 90 days of the executed purchase.
If you are seeking reimbursement, please contact us at info@n-tap.org for guidance and details about the cell line reimbursement program. To request reimbursement, you will need to submit the following:
1. Application form
2. Receipt from ATCC associated with the cell lines purchase
3. Proof of payment
NTAP initiated the 100% reimbursement program for the immortalized human plexiform neurofibroma cells of ATCC to promote plexiform neurofibroma research. Although the reimbursement program is active, we do not reimburse those who ordered only healthy Schwann cell lines (either CRL-3391 or CRL-3392, or both CRL-3391/CRL-3392).
Bulk ordering means when you order at least five cell lines (CRL-3387, -3388, -3389, -3390, -3391, -3392) in the panel. Bulk ordering is available at a discounted price. The price for bulk ordering is $2,800 for academic research and $11,250 for industry.
Yes. Cell lines are $625 for academic research and $2,500 for industry. The price of the cells for academic research is 25% of the industry price.
Reimbursements are:
- For actual costs incurred for the purchase of the product (including taxes and shipping fees). Payments will not be made for indirect costs.
- Capped at $3,500 for nonprofit entities and $12,000 for commercial (i.e., profit) entities within 24 months (based on purchase date) per primary investigator.
- Reimbursements for multiple orders from the same primary investigator within 24 months are allowed. However, they cannot exceed the cap limits noted above.
The reimbursement form is on NTAP’s website here. The document explains the requirements.
Data Sharing
NTAP supports FAIR Data Principles (Findable, Accessible, Interoperable, Reusable) by sharing all NTAP-funded project data.
NTAP engages a third party, Sage Bionetworks (“Sage”), to provide data coordinating services for all NTAP-funded research. Primary Investigators are required, at the direction of NTAP leadership, to provide Sage with all key data generated via NTAP support into a centralized database run by Sage Bionetworks.
NTAP will work together with the Primary Investigator to select what kind of data needs to be uploaded once the project is funded. Data contributors are required to upload the key raw data from their research to enable the data to be analyzed by a third party. This includes any information necessary to interpret the data, such as a description of the cohort or the model system, experimental protocols, descriptions of study instruments and equipment, and code used to generate processed data.
Yes. Uploaded data will be embargoed from the public and accessible only to the data contributor, the NF-OSI data curation team at Sage Bionetworks, or NTAP staff and consultants, during the award period.
This data shall be embargoed and not released by Sage. After the embargo period (18 months after the end date of the award), we will ask that you provide approval for the data to be available on an open platform. However, data will not be released to open access without PI’s approval. The embargo period will end earlier if the data is published or at the data contributor’s discretion.
Yes. Any requests by an investigator for an extension of the embargo period (e.g., due to a delay in primary publication) must be made in writing to the NTAP.
Synapse is a set of web services and tools that make it easier for researchers to aggregate, organize, analyze, and share scientific data, code, and insights.
The NF Data Portal is designed to help openly explore and share NF datasets, analysis tools, resources, and publications related to neurofibromatosis.
NF-OSI stands for Neurofibromatosis Open Science Initiative.