The Mentored Clinical Scientist Development Award

Report
NIH K Awards
K Kiosk - Information about NIH
Career Development Awards
http://http://grants.nih.gov/training/careerdevelopmentawards
Dr. Harry S. Nick, PhD
Professor
January 23, 2013
Why a K award?
To allow a professional candidate,
who has completed training, the opportunity
to transition into a faculty position
and compete at the NIH RO1 level .
All mentored K awards require that the applicant:
 be a U.S. citizen or permanent resident of the U.S.
 be located at a U.S. institution.
 have preliminary data on which to base his/her
hypothesis driven 3-5 year research project in an
area of interest to the NIH Institute.
 have one or more mentors.
 be able to devote, 9 calendar months (75%) effort
to the K-award.
Standard K deadlines (new applications)*: Feb. 12, June 12, and Oct. 12
Types of K Awards
Mentored
K01
K08
K07
K12
K23
K25
K99
Independent
K02
K22
R00
Mid-Career
K24
http://grants.nih.gov/training/careerdevelopmentawards.htm
K08
The Mentored Clinical Scientist Development Award (K08) provides
support to develop outstanding clinician research scientists.
The objective of the NIH Mentored Clinical Scientist Research Career
Development Award (K08) program is to provide salary and research
support for a sustained period of “protected time” (3-5 years) to support
didactic study and/or mentored research for individuals with clinical
doctoral degrees (e.g., M.D., D.D.S., D.M.D., D.O., D.C., O.D., N.D.,
D.V.M., Pharm.D., or Ph.D. in clinical disciplines).
The K08 provides support for an intensive, mentored research career to
develop experience in biomedical or behavioral research, including
translational research leading to research independence.
NIH: Mentored Clinical Scientist Research Career Development Award (Parent K08) (PA11-193) (See NOT-OD-11-063)
NCI: NCI Mentored Clinical Scientist Research Career Development Award to Promote
Diversity (K08) (PAR-12-051)
NIAMS: Mentored Clinical Scientist Research Career Development Award in Muscular
Dystrophy Research (K08) (PA-11-077)
K08 cont.
Candidates for this award must have a clinical doctoral degree and
cannot have been a PI on another NIH grant.
The candidate must identify a mentor or mentoring team who will
supervise the proposed career development and research experience.
The candidate must have a “full-time” appointment at the academic
institution that is the applicant institution (VA appointments must be
discussed with NIH staff).
The total project period may not exceed 5 years.
The salary proposed must be appropriately related to the existing
salary structure.
Applicants must download the SF424 (R&R) application package.
K08 cont.
Application:
•Candidate’s Background
•Career Goals and Objectives
•Career Development/Training Activities During Award Period
•Training in the Responsible Conduct of Research
•Statements by Mentor, Co-mentor(s), Consultants, Contributors
•Description of Institutional Environment
•Institutional Commitment to the Candidate’s Research
Career Development (75% time!)
•Research Strategy
•Appendix
•Letters of Reference
K08 cont.
RESEARCH STRATEGY
A sound research project consistent with the candidate’s level
of research development and career development plan. The
research description should demonstrate the quality of the
candidate’s research, the novelty, significance, creativity and
approach, and the ability of the candidate to carry out the
research. The application must describe the relationship between
the proposed research plan and the mentor’s research.
If more than one mentor is proposed, the respective areas of
expertise and responsibility should be described.
Data and Safety Monitoring (when applicable): Candidates
proposing to conduct clinical trials should consult with relevant
IC staff for specific NIH institute requirements.
Example Specific Aims
Advances in cancer therapy have improved survival rates; however primary ovarian failure and infertility can be major side effects of chemotherapy in
childhood and adult female cancer patients. The associated threat on fertility in patients of reproductive age is often as devastating a psychological factor as the
cancer diagnosis itself. In females, localized radiation treatment or systemic chemotherapy with alkylating agents can lead to chemotherapy-induced amenorrhea
(CIA) and premature menopause through direct effects on primordial follicle (PMF) pools. Cyclophosphamide (CY), as a mainstay in breast cancer treatment, is
most commonly implicated in decreasing ovarian function through direct reduction in PMF pools ( ). CY, a bifunctional alkylating agent, is also given for
treatment of multiple other cancers, lupus erythematosus, and other autoimmune problems with obvious impact on the child bearing decisions of premenopausal
women. Current measures to address chemotherapy-induced infertility involve cryopreservation of ovarian tissues: embryo freezing, oocyte tissue freezing and
oocyte freezing ( ). Our AIMS will address an alternative approach for maintenance of ovarian reserve following CY exposure based on transcriptional
activation of Foxo3a by a specific anti-metabolite, 2-deoxyglucose (2-DG) as adjuvant therapy. Studies in animal models have established that Foxo3a serves as
a critical brake for the activation/transition from primordial to primary follicle. Foxo3a -/- mice exhibit a distinctive ovarian phenotype of global
follicular activation leading to a phenotype indicative of primary ovarian failure and premature menopause. Similarly, female transgenic animals specifically
designed to over-express constitutively active Foxo3a in oocytes were infertile caused by retarded oocyte growth and follicular development, and anovulation.
Our data demonstrate that Foxo3a induction by 2-DG exposure mimics this transgenic model preserving the ovarian reservoir of primordial follicles. The goals
of our AIMS are to evaluate whether 2-DG pretreatment prior to CY exposure can maintain ovarian reserve and thus prevent the fertility issues that haunt
premenopausal women facing cancer or systemic lupus treatment.
Hypothesis I: 2-DG induces ovarian Foxo3a gene expression maintaining ovarian reserve.
AIM IA: To determine both an effective concentration of 2-DG for preserving PMF and timing for pretreatment, female mouse cohorts will be exposed daily to
PBS or dose-escalating 2-DG levels for 1, 2 and 4 weeks. Body weight will be evaluated daily along with effects on estrous cycle with vaginal smears. At
termination, serum estradiol, LH, FSH, inhibin B, and anti-mullerian hormone (AMH) will be evaluated.
AIM IB: One ovary from the animals in AIM IA will be examined histologically for ovarian follicle numbers (total and follicle classes). To address underlying
mechanisms, immunohistochemistry will be used for Foxo3a, relevant signaling molecules, phosphorylated histone H2AX, as well as TUNEL analysis.
AIM IC: The contra lateral ovary will also be employed to address mechanism using realtime RTPCR and immunoblot analysis for Foxo3a and relevant
target/signaling genes.
Hypothesis II: 2-DG induction of ovarian Foxo3a gene expression will prevent CY induced reduction in PMF pools.
AIM IIA: To demonstrate efficacy of 2-DG in preserving PMF pools in reproductive competent mice following CY treatment, groups mice will be pretreated
(1-4 weeks, dose and duration determined in AIM I) with daily IP injection of either PBS or 2-DG alone. A week prior to end of the 2-DG treatment, separate
groups will receive a single injection at two CY concentrations in combination with PBS or 2-DG. Groups from each cohort will be studied at 1, 3 and 6 weeks
after CY injection as described in AIM IA-C.
AIM IIB: To address the consequences of successive CY treatments more analogous to the multiple regimes employed in humans, AIM IIA will be repeated
with the inclusion of two successive injections of CY separated by one week. The total doses and duration will be identical to AIM IIA, with groups from each
cohort studied, as described in AIM IA-C, at 1, 3 and 6 weeks after the last CY injection.
Hypothesis III: 2-DG treatment will preserve fertility and maintain reproductive outcome following CY treatment in young and perimenopausal mice.
AIM IIIA: To demonstrate the ability of 2-DG to preserve fertility in young, reproductive competent mice following CY treatment, the protocol in AIM IIA
will be repeated with mice using the most effective CY concentration. Mice will be then be successively mated to address reproductive outcome and analyzed as
in AIM IA-C after final mating.
AIM IIIB: To address the ability of 2-DG to preserve fertility in "perimenopausal" mice, 6-8 month old mice following CY treatment will be treated as
described in AIM IIIA to address reproductive outcome.
K23
The purpose of the Mentored Patient-Oriented Research Career Development
Award (K23) is to support the career development of investigators who have made
a commitment to focus their research endeavors on patient-oriented research.
The objective of the NIH Mentored Patient-Oriented Research Career
Development Award (K23) program is to provide salary and research support for a
sustained period of “protected time” (3-5 years) to ensure a future cadre of welltrained scientists working in Patient-Oriented Research (POR) who will become
competitive for NIH research project (R01) grant support.
NIH: Mentored Patient-Oriented Research Career Development Award (Parent K23) (PA11-194)(See NOT-OD-11-063)
NCI: NCI Mentored Patient-Oriented Research Career Development Award to Promote
Diversity (K23) (PAR-12-052)
NIAMS: Mentored Patient-Oriented Research Career Development Award in Muscular
Dystrophy Research (K23) (PA-11-076)
NCRR: Translational Scholar Career Awards in Pharmacogenomics and Personalized
Medicine (K23) (PA-11-009). Dual mentors from the Clinical and Translational Science
Awards consortium and the Pharmacogenomics Research Network are required.
Specific Aims-K23 : Dr. Michael Waters, MD/PhD,
Dept. of Neurology, University of Florida
A. Specific Aims
The spinocerebellar ataxias (SCAs) are a diverse group of disorders leading to death of neurons in the cerebellum, brainstem and cerebral cortex.
Identification of SCA mutations has led to novel insights into cerebellar cell death in particular and neuronal death in general. Mutations
identified in the last decade have occurred in a diverse set of genes giving rise to new and in part mutually exclusive hypotheses regarding
neuronal death in these diseases. We have identified mutations in the KCNC3 (Kv3.3) gene, which encodes a voltage-gated potassium channel,
as causative for SCA13. Mutations in this gene have now been identified in two large ataxia kindreds. This proposal aims to test three
hypotheses. 1) The Filipino and French families are affected by SCA13 and represent a unique phenotype requiring definitive characterization.
KCNC3 mutations combine neurodevelopmental and neurodegenerative phenotypes. 2) The R420H Filipino mutation engenders a dominant
negative effect on KCNC3 channel function that may be the result of aberrant channel trafficking. 3) The KCNC3 mutation is likely the cause of
ataxia in uncharacterized SCA patients and specific mutations are reflected by particular phenotypes.
Specific Aim I: Phenotypic characterization of SCA13.
Detailed characterization and refinement of the phenotype remains an important component in defining the clinical correlation to the described
molecular pathology. This is particularly relevant in that the two mutations identified thus far exact profoundly different effects at the cellular
level. Concomitant with this observation is the contrasting phenotypes arising from mutations in the same gene. Despite sharing ataxia and
incoordination, preliminary studies suggest differences regarding age-of-onset, presence of seizures, and cognitive impairment. Increased
precision in describing the phenotype will also further differentiate this ataxia from other SCA phenotypes. Additional clinical characteristics to
be evaluated in affected individuals include: occulomotor pathology, myoclonus, chorea, dystonia, cognitive impairment, auditory pathology,
pyramidal involvement, and peripheral neuropathy. Select patients will also have more formal studies including MR imaging,
electroencephalography, auditory testing, nerve conduction velocities, and nystagmograms. At-risk individuals will be evaluated for subtle
functional impairment and MR imaging abnormalities.
Specific Aim II: Determining the nature of the R420H dominant negative effect.
Preliminary voltage gating studies performed with R420H utilizing a Xenopus laevis oocyte expression system demonstrate a dominant negative
effect of this allele on KCNC3 channel function. It is impossible to determine from these studies the nature of the dominant negative effect.
Possibilities include: 1) aberrant mRNA processing and/or translation, 2) aberrant protein trafficking to the cell membrane, and 3) inherent
channel dysfunction despite proper localization. In an effort to determine if the dominant negative effect results from KCNC3 trafficking errors,
immunocytochemistry with an anti-KCNC3 antibody will be performed on COS-1 cells transiently transfected with R420H mutant constructs.
The model system developed to determine the dominant negative effect of R420H will also be employed to evaluate additional KCNC3
mutations.
Specific Aim III: Genotype/phenotype correlations.
After gene identification, we will analyze a large set of DNA samples for presence of mutations. To this end we will use our own DNA
repository of familial and sporadic ataxia patients without known mutation and samples from a large number of collaborators in the US and
Europe. Over three hundred samples are already in-hand. Phenotypes from mutation-positive patients will be analyzed for features described in
aim 1, and newly discovered mutations will be evaluated as in aim II.
K12
The following Mentored Clinical Scientist Development Program Awards (K12) provide
support to an institution for the development of independent clinical scientists:
NCI: Paul Calabresi Career Development Award for Clinical Oncology (K12) (PAR-10155)
The purpose of the Paul Calabresi Career Development Award in Clinical Oncology
(PCACO) K12 (NIH Institutional Research Career Development K12 grant mechanism) is
to increase the number of clinicians (M.D.s, D.O.s, Pharm.D.s) and basic research
scientists (Ph.D.s. or equivalents) who are trained to design and administer hypothesisbased pilot/Phase I, Phase II, and Phase III cancer therapeutic clinical trials in team
research settings.
NEI: The NEI Mentored Clinical Scientist Development Program Award (K12) (PAR-12002)
NICHD: Child Health Research Career Development Award (CHRCDA) Program [K12]
(RFA-HD-13-011)
NIDA: NIDA Mentored Clinical Scientists Development Program Award in Drug Abuse
and Addiction (K12) (PAR-10-177)
NIDDK: Career Development Programs in Diabetes Research for Behavioral Scientists
(K12) (RFA-DK-11-028)
NIDCR: NIDCR Institutional Career Development Award for Enhancing Research
Capacity in Temporomandibular Joint Disorders and Orofacial Pain (K12) (PAR-11-289)
K18
NIEHS: Short Term Career Development Award in the Environmental Health
Sciences for Established Investigators (K18) (PAR-09-090)
NIH: Career Enhancement Award for Stem Cell Research (K18) (PA-09-110)
NIDCD: NIDCD Research Career Enhancement Award for Established
Investigators (K18) (PAR-10-162)
K24
NIH: Midcareer Investigator Award in Patient-Oriented Research (Parent
K24) (PA-11-195) (See NOT-OD-11-063)
K25
NIH: Mentored Quantitative Research Development Award (Parent K25) (PA-11196) (See NOT-OD-11-063)
K01
The Mentored Research Scientist Development Award (K01) provides an
additional period of sponsored support in an area new to the candidate or in
an area that would enhance the candidate's scientific career.
Candidates who have interrupted their careers for illness or family care may
also apply. Similarly, faculty members at institutions with a substantial
minority enrollment who wish to enhance their research skills may apply.
NIH: Mentored Research Scientist Development Award (Parent K01) (PA-11-190) (See
NOT-OD-11-063)
NCI: NCI Mentored Research Scientist Development Award to Promote Diversity (K01)
(PAR-12-050)
NIDDK: NIDDK Mentored Research Scientist Development Award (K01) (PAR-12-020)
NINDS: NINDS Faculty Development Award to Promote Diversity in Neuroscience
Research (K01) (PAR-12-152)
NIA: Promoting Careers in Aging and Health Disparities Research (K01) (PAR-09-136)
FIC: International Research Scientist Development Award (IRSDA) (K01) (PAR-10-066)
K02
The purpose of the NIH Independent Scientist Award (K02) is
to foster the development of outstanding scientists and enable
them to expand their potential to make significant contributions
to their field of research.
The K02 award provides three, four, or five years of salary
support and “protected time” for newly independent (see IC
provisions) scientists who can demonstrate the need for a period
of intensive research focus as a means of enhancing their
research careers.
Each independent scientist career award program must be
tailored to meet the individual needs of the candidate.
NIH: Independent Scientist Award (Parent K02) (PA-11-191) (See NOT-OD-11-063)
FIC: Independent Scientist in Global Health Award (ISGHA) (K02) (PAR-10-065)
K22
The objective of the NCI Transition Career Development Award
(K22) program is to support mentored, non-independent
investigators in transitioning to their first independent tenure-track
faculty cancer research positions, or their equivalent, with an
enhanced probability of success for obtaining independent NIH or
other research project grant support. MD, MD/PhD, or PhD
NCI: The NCI Transition Career Development Award (K22) (PAR-12-121)
NCI: NCI Transition Career Development Award to Promote Diversity (K22) (PAR-12062)
NHLBI: NHLBI Career Transition Award (K22) (PAR-12-137)
NIAID: NIAID Career Transition Award (K22) (PAR-12-156)
NIDCR: NIDCR Dentist Scientist Career Transition Award for Intramural Investigators
(K22) (PAR-12-004)
NIMH: NIMH Career Transition Award for Intramural Investigators (K22) (PAR-09246)
NINR: NINR Career Transition Award (K22) (PAR-09-067)
NLM: NLM Independent Career Development Award for Biomedical Informatics (K22)
(PAR-10-195)
K99/R00
The K99/R00 award provides up to 5 years of support with two
phases.
The initial mentored phase, provides supports for up to 2 years for
new investigators with no more than 5 years of postdoctoral research
training experience and do not already have a full-time tenure track
assistant professor position. This mentored phase provides time for
additional training, to complete research, to publish results, and
bridge to an independent research position.
The candidate must propose a research project that will be pursued
during the K99 phase and transition into an independent project
during the R00 phase of the award. The individual must select a
mentor with a track record of funded research related to the selected
research topic and experience as a supervisor and mentor. The
sponsoring institution must ensure that the candidate has the
protected time.
K99/R00
Following the mentored phase, the individual may request up to 3
years of support to conduct research as an independent scientist at an
extramural sponsoring institution/organization to which the
individual has been recruited, been offered and has accepted a
tenure-track full-time assistant professor position (or equivalent).
NIH: NIH Pathway to Independence Award (Parent K99/R00) (PA-11197) (See NOT-OD-11-063)
NIDCR: NIDCR Dentist Scientist Pathway to Independence Award
(K99/R00) (PAR-09-256)
NCI: Howard Temin Pathway to Independence Award in Cancer
Research
NIAMS: NIH Pathway to Independence Award in Muscular Dystrophy
Research (K99/R00) (PA-11-078)
Amount of
Funding
per year
Salary
Support
Research/
Training
K01
K08
K23
$50K $150K
($75K)
$20K $50K
($25K)
$75K $105K
($75K)
$20K $90K
($25K)
$75K $180K
($75K)
$25K $50K
($25K)
Ruth L. Kirschstein
National Research Service Award (NRSA)
F Kiosk – Information about Ruth L. Kirschstein
NRSA Individual Fellowship Funding Opportunities
http://grants.nih.gov/training/F_files_nrsa.htm
F32
NIH: Ruth L. Kirschstein National Research Service Awards (NRSA)
for Individual Postdoctoral Fellows (Parent F32) (PA-11-113)
NIAMS: Ruth L. Kirschstein National Research Service Awards for
Individual Postdoctoral Fellowships in Muscular Dystrophy Research
(F32) (PA-11-075)
Research Strategy (Component of Research Training Plan)
Applicant fellows must describe a tailored research training plan including:
• a description of a hypothesis-drivent research strategy suited to the stage of his/her
career development.
• a description of the skills and techniques to be acquired and discuss the relationship of
the proposed research training to the applicant fellow’s career goals.
• the background leading to the proposed research, the significance of the research, the
research approach (design and methods) for achieving the Specific Aims, the rationale,
and expected/alternative outcomes of the proposed studies.
• Inclusion of preliminary data obtained by the applicant fellow in the current or prior
laboratory.
Other Research Experience (Component of Additional Information)
Sponsor(s) and Co-Sponsor(s)
The applicant must identify a sponsor (also called mentor or supervisor) who will
supervise the training and research experience.
Resource Sharing Plan
Appendix
Letters of Reference
Applicant fellows must carefully follow the SF424 (R&R) Individual Fellowship
Application Guide.
T Kiosk - Information about Ruth L. Kirschstein
NRSA Institutional Training Grant Funding
Opportunities
http://grants.nih.gov/training/T_Table.htm
Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training
Grants (T32)
Jointly Sponsored Ruth L. Kirschstein National Research Service Award Institutional
Predoctoral Training Program in the Neurosciences (T32) (PAR-12-084)
Jointly Sponsored Predoctoral Training Program in the Neuroscience).
Predoctoral and Postdoctoral Training Program in Reproductive, Obstetric, Perinatal and
Pediatric Epidemiology and Pharmacoepidemiology (T32)
Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Predoctoral
Training Program in Systems Biology of Developmental Biology & Birth Defects (T32)
Postdoctoral Research Training for Obstetricians and Gynecologists (T32)

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