NINDS-Supported Research Opportunities

1. 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

2. 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

3. 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

4. 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

5. 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.

6. 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 (Oct-Oct), is around 30.69 billion

7. 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

8. NIH Office of the Director National Institutes of Neurological Disorders and Stroke 25 other Institutes and Centers Center for Scientific Review

9. NIH Office of the Director National Institutes of Neurological Disorders and Stroke 25 other Institutes and Centers Center for Scientific Review

10. Center for Scientific Review Study Section A Study Section B Study Section C

11. NIH Office of the Director National Institutes of Neurological Disorders and Stroke 25 other Institutes and Centers Center for Scientific Review

12. National Institutes of Neurological Disorders and Stroke Extramural Research Intramural Research Training Etc.

13. 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

14. 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

15. 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 section • Discuss research plan • After Review: • Often can read between lines of summary statement

16. 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

17. 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

18. 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

19. Review Process for a Research Grant National Institutes of Health Research Grant Application School or Other Research Center Center for Scientific Review Assigns to IRG/Study Section & IC Study Section Initiates Research Idea Submits Application Evaluates for Scientific Merit Institute Evaluates for Program Relevance Advisory Councils and Boards Allocates Funds Conducts Research Recommends Action Institute Director Takes final action for NIH Director

20. NIH Application Formats

21. New Review Criteria

23. When Preparing an Application • 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

24. What NIH does • Funds hypothesis driven basic (laboratory) • “Basic” such as cellular, molecular, or anatomical… • Funds clinical science • Including clinical trials, epidemiology • Funds contracts for science, infrastructure • Translational research • Therapeutics Development • Note: not all clinical research = clinical trials

25. Examples of Clinical Research Clinical Trials Imaging Studies Natural History Studies Epidemiology/Genetic Epidemiology Gene discovery (families, individuals)

26. 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

27. 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

28. 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 $24M FY2012 $24M

29. 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

30. 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: 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

31. 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

32. NINDS Office of Translational Research • Welcome to Dr. Rajesh Ranganathan. • Joined NINDS in January as the Director of the NINDS Office of Translational Research

33. 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.htmlNINDS 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

34. Potential Translational Project Activities • Primary and Secondary Screens • Animal Efficacy • Therapeutic Optimization • Formulation • Pharmacokinetics • Pharmacodynamics • Toxicology • IND Application (final milestone)

35. 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/20101217-NEXT.htm • Contact: • Elizabeth McNeil, MD MScNational Institute of Neurological Disorders and StrokePhone: (301) 496-9135E-mail: mcneilde@ninds.nih.gov  or  NEXT@ninds.nih.gov

36. 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

37. 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

38. 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

39. 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

40. NeuroNEXT Coordinating Centers and Clinical Sites

41. 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

45. Click on Results and See Recent Publications

46. 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

49. 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 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.

50. Thank you!