NINDS-Supported Research
Opportunities
Jill A. Morris, Ph.D.
Program Director
Neurogenetics Cluster
National Institute of Neurological Disorders and
Stroke
National Institutes of Health
jill.morris@nih.gov
Today's Goals
Introduction
 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 & 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

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Research Is Important and
It Can Cure Diseases
• My Family Member is Sick
•The Government Should Help
Find Cures
• The National Institutes of
Health Should Help Lead This
Effort
The NIH Should Encourage &
Support the Best Science
 NIH’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 Budget
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 (OctOct), is around 30.69 billion
NIH is a BIG “place”
NIH has 27 Institutes & Centers with:
• Different missions & priorities
• 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 Subcultures
NIH Office
of the
Director
Center for
Scientific
Review
National
Institutes of
Neurological
Disorders
and Stroke
25 other
Institutes
and
Centers
NIH Office
of the
Director
Center for
Scientific
Review
National
Institutes of
Neurological
Disorders
and Stroke
25 other
Institutes
and
Centers
Center for
Scientific
Review
Study
Section
A
Study
Section
B
Study
Section
C
NIH Office
of the
Director
Center for
Scientific
Review
National
Institutes of
Neurological
Disorders
and Stroke
25 other
Institutes
and
Centers
National
Institutes of
Neurological
Disorders and
Stroke
Extramural
Research
Intramural
Research
Training
Etc.
Intramural Vs. Extramural

NIH 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 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 Director
Be Helpful to an Investigator?
◦ Prior to submission:

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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 Mechanisms
 Research
Series
 R01 is “bread and butter” application, faculty
 Many others exist (R13, R21)
 Not all Institutes support all Mechanisms!
 Career
and Training Grants
 Also called NRSA (National Research Service
Awards).
 T series: given to Departments
 F series: residency/fellowship, pre, post doc
 K series: patient oriented (doctor interacts with
patient)-residency, fellowship
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
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 Grant
National Institutes of Health
Research
Grant
Application
Initiates
Research
Idea
School or Other
Research Center
Center for Scientific Review
Assigns to IRG/Study Section & IC
Study Section
Submits Application
Evaluates for Scientific Merit
Institute
Evaluates for Program Relevance
Advisory Councils and Boards
Conducts
Research
Allocates Funds
Recommends Action
Institute Director
Takes final action for NIH Director
NIH Application Formats
NEW 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 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 Application

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Plan WELL in advance
Read instructions, follow the format
Explicitly state the rationale
Include well-designed, clearly labeled tables and
figures
Present an organized, lucid write-up
Never Assume that Reviewers “will know what you
mean”
Refer to literature thoroughly and thoughtfully
Review NIH Reporter for already funded efforts
What NIH does

Funds hypothesis driven basic (laboratory)
◦ “Basic” such as cellular, molecular, or
anatomical…

Funds clinical science
◦ Including clinical trials, epidemiology

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Funds contracts for science, infrastructure
Translational research
◦ Therapeutics Development

Note: not all clinical research = clinical trials
Examples of Clinical Research
Clinical Trials
 Imaging Studies
 Natural History Studies
 Epidemiology/Genetic Epidemiology
 Gene discovery (families, individuals)

Some things NIH doesn’t
typically 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 source
Other Government agencies
 Pharmaceutical
 Foundations

◦ Important ways to fund collecting preliminary
data
◦ Important ways to ask questions the NIH
doesn’t typically fund
Neurofibromatosis Research at NIH

RCDC (Research, Condition, Disease Category
reporting) on TSC:
http://report.nih.gov/rcdc/categories/
FY2009
FY2009
FY2010
FY2010
FY2011
FY2012
$17M (non-ARRA)
$2M (ARRA)
$24M (non-ARRA)
$1M (ARRA)
$24M
$24M
Institutes

The 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)
Neurofibromatosis
16
Tuberous Sclerosis
10
*epileptogenesis
2
*autism
4
Glial Biology
Vanishing White Matter Disease
Brain Malformations (Cerebellar Malformations,
55
3
17
Spina 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 Cluster

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
Research
Welcome to Dr. Rajesh Ranganathan.
 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.html
http://grants.nih.gov/grants/guide/pa-files/PAR-08-233.html
http://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
Activities
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Primary and Secondary Screens
Animal Efficacy
Therapeutic Optimization
Formulation
Pharmacokinetics
Pharmacodynamics
Toxicology
IND Application (final milestone)
NeuroNEXT: Network for Excellence
In Neuroscience Clinical 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/2010121
7-NEXT.htm
 Contact:
 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 Goals

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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
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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
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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)
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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 NIH
Grants
NIH Reporter
 www.projectreporter.nih.gov
 You can choose the parameters for the
search
 Read 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 Resource
Clinicaltrials.gov
 http://clinicaltrials.gov/
 Not just NIH funded trials

◦ All NIH funded trials
◦ Those being run by other organizations,
including pharmaceutical companies
Take Home Message:
Neurofibromatosis research is moving
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 cuttingedge 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!