NINDS-Supported Research OpportunitiesJill A. Morris, Ph.D.Program DirectorNeurogenetics ClusterNational Institute of Neurological Disorders and StrokeNational Institutes of Healthjill.morris@nih.gov

Today's GoalsIntroduction Give a brief overview of the intricacies of NIH: the gold standard for research fundingDiscuss some specifics of Neurofibromatosis research funding at NIH and NINDSSuggest a few resources to help you learn more if you have an interest

Brief History & Interests1997-1998: Senior Staff Fellow, Developmental and Metabolic Neurology Branch, NINDS, NIH, Bethesda, MD. Research: Niemann-Pick Type C

1998-2003: Senior Research Biologist, Department of Neuroscience, Merck Research Laboratories, Merck & Co., West Point, PA. Research: Alzheimers, Parkinsons, Bipolar Disorder and Schizophrenia

2003 to 2011: Assistant Professor of Pediatrics, Northwestern University and Childrens Memorial Research Center, Chicago, IL. Research: Molecular Basis of Neurodevelopmental Disorders including autism and schizophrenia

2011 to present: Program Director, Neurogenetics, NINDS, NIH.Promote interactions between investigators with different expertise to drive translationInterest in neurodevelopmental disorders, intellectual disabilities, cognition, molecular mechanisms of disease, translational research

Research Is Important and It Can Cure Diseases My Family Member is SickThe Government Should Help Find Cures The National Institutes of Health Should Help Lead This Effort

The NIH Should Encourage & Support the Best ScienceNIHs mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce the burdens of illness and disability.

Comments on the NIH BudgetNIH is part of a much larger federal government agency (DHHS).Congress oversees all federal agencies. (And sets their budgets!)NIH is NOT immune to political pressures.NIH employees (and other federal employees) are forbidden from lobbying congress for any given area of research. NIH Budget: in Fiscal Year (FY) 2012 (Oct-Oct), is around 30.69 billion

NIH is a BIG placeNIH has 27 Institutes & Centers with: 3-5 letter abbreviations; NINDS, NCI, NIDDK Different budgets Different ways of doing things (e.g. deciding which grants to fund). Different Strategic Plans Different missions & priorities Different Subcultures

NIH Office of the DirectorCenter for Scientific ReviewNational Institutes of Neurological Disorders and Stroke25 other Institutes and Centers

NIH Office of the DirectorCenter for Scientific ReviewNational Institutes of Neurological Disorders and Stroke25 other Institutes and Centers

StudySection ACenter for Scientific ReviewStudySection BStudySection C

NIH Office of the DirectorCenter for Scientific ReviewNational Institutes of Neurological Disorders and Stroke25 other Institutes and Centers

Extramural ResearchIntramural ResearchTrainingEtc.National Institutes of Neurological Disorders and Stroke

Intramural Vs. ExtramuralNIH is divided into INTRAMURAL and EXTRAMURAL componentsIntramural: comparable to an academic medical center and Research InstitutionDoes its own research, has investigators testing hypotheses, laboratories, clinical trials (at the clinical center)Extramural:Where I workManages grants and contractsAdministration of grants across the country/globally which are funded by NIH

Whos who- Extramural NIH Staff?Program Staff (PD) also called PO- PhD or MDassist applicants, develop initiatives, review progress reports, approve fundingReview Staff (SRA) PhDorganizes review of applications (study sections), write summary statementsGrants management (GMB) accounting, administrative, clericalsend out the checksAssures compliance with regulations of grants, reciept of documentsContracts BranchWorks with Program to Manage Contracts

How (when) Can Program Director Be Helpful to an Investigator?Prior to submission:Is your project in the mission of the IC?Is there an initiative appropriate for this project?Help find appropriate study sectionDiscuss research planAfter Review:Often can read between lines of summary statement

Grant MechanismsResearch SeriesR01 is bread and butter application, facultyMany others exist (R13, R21)Not all Institutes support all Mechanisms!Career and Training GrantsAlso called NRSA (National Research Service Awards).T series: given to DepartmentsF series: residency/fellowship, pre, post docK series: patient oriented (doctor interacts with patient)-residency, fellowship

R Series R01- bread and butterTypically 4-5 years12 pagesR21- high risk, high payoffTwo years, $200K (DC) per year, no more than $275K total6 pagesNot all institutes use, or not clinical researchR03-smaller projects2 years, 50K per yearnot all institutes use in same way/accept6 pages

How is a research grant funded?Most Research Should be Investigator InitiatedA Little Should be Program DirectorAll of It Should be Peer-Reviewed

Review Process for a Research Grant

NIH Application Formats

NEW SectionsOLD SectionsINTRODUCTION-Revision (1 page)INTRODUCTION-Resubmission (3 pages)SPECIFIC AIMS (1 page)SPECIFIC AIMS (1 page)RESEARCH STRATEGY (R01-12 PAGES)R01 12 pagesSignificanceBackground and SignificanceInnovationApproach-Research Design and Methods -(preliminary studies-part of approach)Preliminary Studies -(progress report-part of approach)Progress report

New Review Criteria

New Review CriterionSection of New ApplicationOverall ImpactEntire ApplicationSignificanceResearch Strategy (Significance, all)InvestigatorKey Personnel Profile/BiosketchInnovationResearch Strategy (Innovation, Approach)ApproachResearch Strategy (Approach)EnvironmentOther Project Information (Facilities & Other Resources)

When Preparing an ApplicationPlan WELL in advanceRead instructions, follow the formatExplicitly state the rationaleInclude well-designed, clearly labeled tables and figuresPresent an organized, lucid write-upNever Assume that Reviewers will know what you meanRefer to literature thoroughly and thoughtfullyReview NIH Reporter for already funded efforts

What NIH doesFunds hypothesis driven basic (laboratory)Basic such as cellular, molecular, or anatomicalFunds clinical scienceIncluding clinical trials, epidemiologyFunds contracts for science, infrastructureTranslational researchTherapeutics DevelopmentNote: not all clinical research = clinical trials

Examples of Clinical ResearchClinical TrialsImaging StudiesNatural History StudiesEpidemiology/Genetic EpidemiologyGene discovery (families, individuals)

Some things NIH doesnt typically FundTrain individuals for clinical practiceSponsor patient/family/clinical meetings (do co-sponsor research meetings)Pay for routine or typical care

NIH is not the only funding sourceOther Government agenciesPharmaceuticalFoundationsImportant ways to fund collecting preliminary dataImportant ways to ask questions the NIH doesnt typically fund

Neurofibromatosis Research at NIH RCDC (Research, Condition, Disease Category reporting) on TSC: http://report.nih.gov/rcdc/categories/ FY2009$17M (non-ARRA)FY2009 $2M (ARRA)FY2010$24M (non-ARRA)FY2010 $1M (ARRA)FY2011$24MFY2012$24M

InstitutesThe National Institute of Neurological Disorders and Stroke (NINDS) is only one of the many Institutes funding Neurofibromatosis ResearchAlso funded by other ICs including: NCI (National Cancer Institute)-especially tumor biologyNIDCD (Deafness and Other Communication Disorders Institute)- cellular signals that lead to tumors that cause NF2 and potential treatments NIMH (Mental Health)- neuronal signaling

Grants Portfolio (2012)Neurofibromatosis 16 Tuberous Sclerosis 10*epileptogenesis 2*autism 4Glial Biology 55Vanishing White Matter Disease 3Brain Malformations (Cerebellar Malformations, 17Spina Bifida, Neural Tube Defects)Hydrocephalus 5 Mechanisms: F30, F31, F32, K08, K23, K99, L30, P01, P50, R01, R03, R13, R21, R37, R42, R43, R44, R56, RC1, U01 Lead on Trans-NIH working groups for TSC and NF; Co-Lead on Trans-NIH Hydrocephalus and Hindbrain Malformations Working Group; Interactions with advocacy groups/ foundations

NINDS MISSION/Neurogenetics ClusterMission: The mission of NINDS is to reduce the burden of neurological disease - a burden borne by every age group, by every segment of society, by people all over the world.

Neurogenetics Cluster: Translational research to link results of basic research in inherited neurological disorders to medication development and clinical trials.

Overlapping NINDS Diseases/Research Areas with other Clusters:Brain Tumor, Neuronal Signaling, and Cognition

NINDS Office of Translational ResearchWelcome to Dr. RajeshRanganathan. Joined NINDS in January as the Director of the NINDS Office of Translational Research

Translational NINDS Initiatives:Funding for Therapeutic Development Projects NINDS Cooperative Program in Translational Research (U01, U24, U54) Funding for full-scale single component and multi-component research projects and resource centers directed at developing new therapies. http://grants.nih.gov/grants/guide/pa-files/PAR-08-234.htmlhttp://grants.nih.gov/grants/guide/pa-files/PAR-08-233.htmlhttp://grants.nih.gov/grants/guide/pa-files/PAR-08-236.html NINDS Exploratory/Developmental Projects in Translational Research (R21) Funding for pilot projects to generate tools and proof-of-principle for therapeutics development. http://grants.nih.gov/grants/guide/pa-files/PAR-08-232.html NINDS Cooperative Small Business Awards In Translational Research (SBIR/U44) http://grants.nih.gov/grants/guide/pa-files/PAR-08-235.html

Potential Translational Project ActivitiesPrimary and Secondary ScreensAnimal EfficacyTherapeutic OptimizationFormulationPharmacokineticsPharmacodynamicsToxicologyIND Application (final milestone)

NeuroNEXT: Network for Excellence In Neuroscience Clinical TrialsA robust, standardized, and accessible infrastructure to facilitate rapid development and implementation of protocols in neurological disorders affecting adult and/or pediatric populations. The network includes multiple Clinical Sites, one Clinical Coordinating Center (CCC) and one Data Coordinating Center (DCC).

Website: http://www.ninds.nih.gov/news_and_events/proceedings/20101217-NEXT.htmContact:Elizabeth McNeil, MD MSc National Institute of Neurological Disorders and Stroke Phone: (301) 496-9135 E-mail: mcneilde@ninds.nih.gov or NEXT@ninds.nih.gov

NeuroNEXT GoalsTest highly promising therapies in phase II clinical trials, increasing the impact of NINDS funded clinical researchAccelerate drug development through an established clinical trials infrastructureDecrease the time/cost between trial design and trial completionCoordinate public/private sector efforts by leveraging NINDS existing relationships with academic investigators and patient advocacy groups and engage industry participation

NeuroNEXT: Network Designed to Efficiently Conduct Phase II Clinical Trials

Central IRBMaster Contract25 experienced, well trained sites throughout the United StatesExperienced Clinical and Data Coordinating Centers to help investigators bring new therapies forward

NeuroNEXT Network InfrastructureNIH/ NINDSElizabeth McNeil, MD, MScClaudia Moy, PhDClinical Coordinating CenterMassachusetts General HospitalMerit Cudkowicz, MD, MScData Coordinating CenterUniversity of IowaChristopher Coffey, PhD

Clinical Study SitesAlbert Einstein College of Medicine-YeshivaChildrens of BostonChildrens NationalColumbia-CornellEmoryMassachusetts General HospitalNorthwestern UniversityOhio State UniversityOregon Health and Science UniversitySwedish Health Services (Seattle)SUNY (Buffalo, Downstate, Upstate, and Stony Brook)

University of Alabama, BirminghamUniversity of California, DavisUCLAUniversity of CincinnatiUniversity of Colorado, DenverUniversity of Kansas University of MiamiUniversity of PittsburghUniversity of RochesterUniversity of UtahUniversity of VirginiaUniversity of Texas, DallasVanderbiltWashington University in St. Louis

NeuroNEXT Coordinating Centers and Clinical Sites

You can Look At the Funded NIH Grants NIH Reporterwww.projectreporter.nih.govYou can choose the parameters for the searchRead individual abstracts, see budget totals, see publications for an individual project that NIH is currently funding

Click on Results and See Recent Publications

Another Great ResourceClinicaltrials.govhttp://clinicaltrials.gov/Not just NIH funded trialsAll NIH funded trialsThose being run by other organizations, including pharmaceutical companies

Take Home Message: Neurofibromatosis research is moving forwardWe have extremely strong basic scienceThis will allow development of small molecule targets for therapy (medication development)NINDS supports two P50 grants for NF Centers. Investigators at these highly interactive and multidisciplinary centers collaborate to perform cutting-edge basic and translational NF research. NINDS funds a translational U01.Examining a mouse model of plexiform neurofibromas to test existing preclinical compounds and phase 1-3 drugs that were developed for other uses.

Thank you!

e*Total NIH budget was more than $20 B in FY01 There were approximately 40K applicationsICs are thematically organized around disorders (e.g. cancer, diabetes, stroke); organ system (heart/lung/blood, eye, musculoskeletal); or service function (NCRR, CSR, CIT)

*Ignore grantsmanship at your own peril.In essence you're asking a complete or relative stranger to convince a group of other strangers for hundreds of thousands of dollars!The decision is a bet. It's as much about you as about the specific scientific proposal.**