NINDS-Supported NINDS-Supported Research OpportunitiesResearch Opportunities

Jill A. Morris, Ph.D.Program Director

Neurogenetics ClusterNational Institute of Neurological

Disorders and StrokeNational Institutes of Health

jill.morris@nih.gov

Today's GoalsToday's GoalsIntroduction Give a brief overview of the

intricacies of NIH: the “gold standard” for research funding

Discuss some specifics of Neurofibromatosis research funding at NIH and NINDS

Suggest a few resources to help you learn more if you have an interest

Brief History & InterestsBrief History & Interests 1997-1998: 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: Alzheimer’s, Parkinson’s, Bipolar Disorder and Schizophrenia

2003 to 2011: Assistant Professor of Pediatrics, Northwestern University and Children’s 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

translation Interest in neurodevelopmental disorders, intellectual disabilities, cognition,

molecular mechanisms of disease, translational research

Research Is Important and Research Is Important and It Can Cure DiseasesIt Can Cure Diseases

• My Family Member is My Family Member is SickSick•The Government Should The Government Should Help Find CuresHelp Find Cures• The National Institutes The National Institutes of Health Should Help of Health Should Help Lead This EffortLead This Effort

The NIH Should The NIH Should Encourage & Support the Encourage & Support the Best ScienceBest ScienceNIH’s 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 Comments on the NIH BudgetBudget

NIH 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 NIH is a BIG “place”“place”

NIH has 27 Institutes & Centers with:NIH 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 Director

Center for

Scientific Review

National Institutes

of Neurologic

al Disorders

and Stroke

25 other Institute

s and Centers

NIH Office of

the Director

Center for

Scientific Review

National Institutes

of Neurologic

al Disorders

and Stroke

25 other Institute

s and Centers

StudySection

A

Center for

Scientific Review

StudySection

B

StudySection

C

NIH Office of

the Director

Center for

Scientific Review

National Institutes

of Neurologic

al Disorders

and Stroke

25 other Institute

s and Centers

Extramural

Research

Intramural

Research

TrainingEtc.

National Institutes

of Neurological Disorders and Stroke

Intramural Vs. Intramural Vs. ExtramuralExtramuralNIH is divided into INTRAMURAL and

EXTRAMURAL components◦Intramural:

comparable to an academic medical center and Research Institution

Does its “own” research, has investigators testing hypotheses, laboratories, clinical trials (at the clinical center)

◦Extramural: Where I work Manages grants and contracts “Administration” of grants across the

country/globally which are funded by NIH

Who’s who- Extramural NIH Who’s who- Extramural NIH Staff?Staff?

◦ Program Staff (PD) also called PO- PhD or MD

assist applicants, develop initiatives, review progress reports, approve funding

Review Staff (SRA) – PhD organizes review of applications (study

sections), write summary statements

Grants management (GMB) – accounting, administrative, clerical send out the checks Assures compliance with regulations of grants,

reciept of documents

Contracts Branch Works with Program to Manage Contracts

How (when) Can Program How (when) Can Program Director Be Helpful to an Director Be Helpful to an Investigator?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 section Discuss research plan

◦After Review: Often can read between lines of

summary statement

Grant MechanismsGrant Mechanisms Research Series

R01 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 R Series R01- “bread and butter”

Typically 4-5 years 12 pages

R21- “high risk, high payoff” Two years, $200K (DC) per year, no more than $275K total

6 pages Not all institutes use, or not clinical research

R03-smaller projects 2 years, 50K per year not all institutes use in same way/accept 6 pages

How is a research grant How is a research grant funded?funded?

Most Research Should be Investigator Initiated

A Little Should be Program Director

All of It Should be Peer-Reviewed

Review Process for a Research GrantReview Process for a Research GrantNational Institutes of Health

Center for Scientific ReviewSchool or Other

Research Center

Submits Application

Allocates Funds

ResearchGrant

Application

InitiatesResearchIdea

ConductsResearch

Study Section

Evaluates for Scientific Merit

Institute

Evaluates for Program Relevance

Advisory Councils and Boards

Recommends Action

Institute DirectorTakes final action for NIH Director

Assigns to IRG/Study Section & IC

NIH Application FormatsNIH Application FormatsNEW Sections OLD Sections

INTRODUCTION-Revision (1 page) INTRODUCTION-Resubmission (3 pages)

SPECIFIC AIMS (1 page) SPECIFIC AIMS (1 page)

RESEARCH STRATEGY (R01-12 PAGES)

R01 12 pages

Significance Background and Significance

Innovation

Approach- Research Design and Methods

-(preliminary studies-part of approach)

Preliminary Studies

-(progress report-part of approach)

Progress report

New Review CriteriaNew Review Criteria

New Review Criterion Section of New Application

Overall Impact Entire Application

Significance Research Strategy (Significance, all)

Investigator Key Personnel Profile/Biosketch

Innovation Research Strategy (Innovation, Approach)

Approach Research Strategy (Approach)

Environment Other Project Information (Facilities & Other Resources)

When Preparing an When Preparing an ApplicationApplication

Plan 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

mean”Refer to literature thoroughly and thoughtfullyReview NIH Reporter for already funded efforts

What NIH doesWhat NIH doesFunds hypothesis driven basic

(laboratory)◦“Basic” such as cellular, molecular, or

anatomical…Funds clinical science

◦ Including clinical trials, epidemiologyFunds contracts for science, infrastructureTranslational research

◦Therapeutics DevelopmentNote: not all clinical research = clinical

trials

Examples of Clinical Examples of Clinical ResearchResearchClinical TrialsImaging StudiesNatural History StudiesEpidemiology/Genetic

EpidemiologyGene discovery (families,

individuals)

Some things NIH doesn’t Some things NIH doesn’t typically Fundtypically Fund

Train individuals for clinical practice

Sponsor patient/family/clinical meetings (do co-sponsor research meetings)

Pay for routine or typical care

NIH is not the only funding NIH is not the only funding sourcesourceOther Government agenciesPharmaceuticalFoundations

◦Important ways to fund collecting preliminary data

◦Important ways to ask questions the NIH doesn’t typically fund

Neurofibromatosis Research Neurofibromatosis Research at NIH 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

InstitutesInstitutesThe National Institute of Neurological

Disorders and Stroke (NINDS) is only one of the many Institutes funding Neurofibromatosis Research◦Also funded by other ICs including:

NCI (National Cancer Institute)-especially tumor biology

NIDCD (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)Grants Portfolio (2012)Neurofibromatosis 16

Tuberous Sclerosis 10

*epileptogenesis 2

*autism 4

Glial Biology 55

Vanishing White Matter Disease 3

Brain Malformations (Cerebellar Malformations, 17

Spina Bifida, Neural Tube Defects)

Hydrocephalus 5

• Mechanisms:Mechanisms: F30, F31, F32, K08, K23, K99, L30, P01, F30, F31, F32, K08, K23, K99, L30, P01, P50, R01, R03, R13, R21, R37, R42, R43, R44, R56, RC1, P50, R01, R03, R13, R21, R37, R42, R43, R44, R56, RC1, U01U01

• 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 NINDS’ MISSION/Neurogenetics ClusterCluster

Mission: 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 NINDS Office of Translational ResearchResearch

Welcome to Dr. Rajesh Ranganathan. Joined NINDS in January as the

Director of the NINDS Office of Translational Research

Translational NINDS Translational NINDS Initiatives: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 Potential Translational Project ActivitiesActivities

Primary and Secondary ScreensAnimal EfficacyTherapeutic OptimizationFormulationPharmacokineticsPharmacodynamicsToxicologyIND Application (final milestone)

NeuroNEXT: Network for NeuroNEXT: Network for Excellence In Neuroscience Excellence In Neuroscience Clinical TrialsClinical Trials A 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.htm

Contact: Elizabeth McNeil, MD MSc

National Institute of Neurological Disorders and StrokePhone: (301) 496-9135E-mail: mcneilde@ninds.nih.gov  or  NEXT@ninds.nih.gov

NeuroNEXT Goals

Test highly promising therapies in phase II clinical trials, increasing the impact of NINDS funded clinical research

Accelerate drug development through an established clinical trials infrastructure

Decrease the time/cost between trial design and trial completion

Coordinate 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 IRB Master Contract 25 experienced, well trained sites throughout the

United States Experienced Clinical and Data Coordinating Centers

to help investigators bring new therapies forward

NeuroNEXT Network Infrastructure

NIH/ NINDS Elizabeth McNeil, MD, MSc Claudia Moy, PhD

Clinical Coordinating Center Massachusetts General Hospital

Merit Cudkowicz, MD, MSc

Data Coordinating Center University of Iowa

Christopher Coffey, PhD

Clinical Study Sites Albert Einstein College of

Medicine-Yeshiva Childrens of Boston Children’s National Columbia-Cornell Emory Massachusetts General Hospital Northwestern University Ohio State University Oregon Health and Science

University Swedish Health Services (Seattle) SUNY (Buffalo, Downstate,

Upstate, and Stony Brook)

University of Alabama, Birmingham

University of California, Davis UCLA University of Cincinnati University of Colorado, Denver University of Kansas University of Miami University of Pittsburgh University of Rochester University of Utah University of Virginia University of Texas, Dallas Vanderbilt Washington University in St. Louis

NeuroNEXT Coordinating Centers and Clinical Sites

You can Look At the Funded You can Look At the Funded NIH Grants 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 Click on Results and See Recent PublicationsRecent Publications

Another Great ResourceAnother Great ResourceClinicaltrials.govhttp://clinicaltrials.gov/Not just NIH funded trials

◦All NIH funded trials◦Those being run by other

organizations, including pharmaceutical companies

Take Home Message: Take Home Message: Neurofibromatosis research is Neurofibromatosis research is moving forwardmoving forward

We have extremely strong basic science◦ This 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!Thank you!