Full Text HL-96-013
 
MITOCHONDRIAL DNA MUTATIONS IN HEART, LUNG AND BLOOD DISEASES
 
NIH Guide, Volume 25, Number 26, August 2, 1996
 
RFA:  HL-96-013
 
P.T. 34

Keywords: 
  Nucleic Acids 
  Cardiovascular Diseases 
  Blood Diseases 
  Pulmonary Diseases 

 
National Heart, Lung, and Blood Institute
 
Letter of Intent Receipt Date:  January 24, 1997
Application Receipt Date:  March 12, 1997
 
THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  THE FULL
RFA INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION
INSTRUCTIONS AND MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE
TO THIS RFA.
 
PURPOSE
 
This initiative will foster research on molecular, cellular, genetic,
and epidemiologic approaches to elucidate the role of mitochondrial
DNA (mtDNA) mutations in heart, blood vessels, blood and lung
diseases.  Its goals are to define mechanisms by which mtDNA
mutations cause tissue-specific, progressive diseases, and to
elucidate the cause and effect relationships between alterations in
this genome and pathological phenotypes.  The ultimate purpose of
this initiative is the development of effective strategies for
prevention and treatment of cardiovascular, pulmonary, and
hematologic disorders due to mitochondrial DNA mutations in humans.
Although this Request for Applications (RFA) is sponsored by the
National Heart, Lung, and Blood Institute (NHLBI), other Institutes
and Centers of the NIH may also have an interest in mitochondrial
research.  Applications will be assigned to the most appropriate
Institute/Center on the basis of established PHS referral guidelines.
 
HEALTHY PEOPLE 2000
 
The Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2000,"
a PHS-led national activity for setting priority areas.  This Request
for Applications (RFA), Mitochondrial DNA Mutations in Heart, Blood
and Lung Diseases, is related to the priority areas of heart disease
and stroke, diabetes and chronic disabling conditions, and
environmental health.  Potential applicants may obtain a copy of
"Healthy People 2000" (Full Report:  Stock No. 017-001-00474-0 or
Summary Report: Stock No. 017-001-00473-1) through the Superintendent
of Documents, Government Printing Office, Washington, DC 20402-9325
(telephone 202-512-1800).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for-profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, units of State and local
governments, and eligible agencies of the Federal government.
Racial/ethnic minority individuals, women, and persons with
disabilities are encouraged to apply as Principal Investigators.
 
All current policies and requirements that govern the research grant
programs of the NIH will apply to grants awarded under this RFA.
Awards under this RFA to foreign institutions will be made only for
research of very unusual merit, need, and promise, and in accordance
with Public Health Service policy governing such awards.
 
MECHANISM OF SUPPORT
 
This RFA will use the NIH individual research project grant (R01)
mechanism of support.  Newly independent investigators who wish to
apply are encouraged to consult with a program representative (see
INQUIRIES below).  Specific application instructions have been
modified to reflect "MODULAR GRANT" and "JUST-IN-TIME" streamlining
efforts being examined by the NIH.  The "MODULAR GRANT" concept
establishes specific modules (increments) in which direct costs may
be requested as well as a maximum level for requested budgets.  Only
limited budgetary information is required under this approach.  The
"JUST-IN-TIME" concept allows applicants to submit certain
information only when there is a possibility for an award.  It is
anticipated that these changes will reduce the administrative burden
for the applicants, applicant institutions, reviewers, and Institute
staff.
 
For this RFA, funds must be requested in $25,000 direct cost modules.
Up to a maximum of seven modules ($175,000 direct costs) per year may
be requested.  A feature of the modular grant concept is that no
escalation is provided for future years, and all anticipated expenses
for all years of the project must be included within the number of
modules being requested.  Only limited budget information will be
required and any budget adjustments made by the Initial Review Group
will be in modules of $25,000.  Instructions for completing the
Biographical Sketch have also been modified.  In addition, Other
Support information and the application Checklist page are not
required as part of the initial application.  If there is a
possibility for an award, necessary budget, Other Support, and
Checklist information will be requested by NHLBI staff following the
initial review.  The APPLICATION PROCEDURES section of this RFA
provides specific details of modifications to standard PHS 398
application kit instruction.
 
Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant. The total
project period for an application submitted in response to this RFA
may not exceed four years.
 
This RFA is a one-time solicitation.  Future unsolicited competing
continuation applications will compete with all
investigator-initiated applications and be reviewed according to the
customary peer review procedures.  It is anticipated that support for
this program will begin in September 1997.  Administrative
adjustments in project period and/or amount may be required at the
time of the award.
 
FUNDS AVAILABLE
 
It is anticipated that for fiscal year 1997, approximately $1,800,000
total costs will be available for the first year of support for this
initiative.  Award of grants pursuant to this RFA is contingent upon
receipt of such funds for this purpose.  It is anticipated that
approximately six new grants will be awarded under this program.  The
specific number to be funded will, however, depend on the merit and
scope of the applications received and on the availability of funds.
Direct costs will be awarded in modules of $25,000, less any overlap
or other necessary administrative adjustments.  Indirect costs will
be awarded based on the negotiated rates.
 
RESEARCH OBJECTIVES
 
Background
 
There is now convincing evidence that proper functioning of human
mitochondrial DNA (mtDNA) is critical to normal cellular metabolism
and that mutations in mtDNA can result in severe disease phenotypes.
Recently, a large number of mtDNA mutations have been catalogued and
linked to human degenerative diseases.  Mitochondrial defects may be
inherited or acquired.  Phenotypic abnormalities in individuals
bearing genetic defects may be evident at birth or may not be
apparent until middle age.  Although it is clear that mutations in
mtDNA can cause devastating symptoms affecting different organ
systems, many clinically relevant questions concerning
pathophysiology remain unanswered.  Quantitative relationships
between the abundance of mutated forms of mtDNA relative to normal
mitochondrial genome and dysfunction of different cell types remain
to be defined.
 
In terms of cardiovascular diseases, evidence suggests that an
accumulation of mutant forms of mtDNA in the myocardium frequently
results in cardiac conduction block and sudden cardiac death.  It is
apparent that certain types of cardiac diseases may be caused by the
mtDNA mutations, but the pathophysiological events that give rise to
specific forms of heart disease in association with these mtDNA
mutations still remain obscure.  The current view is that
abnormalities in mitochondrial structure and function, and mutations
in mtDNA are associated with a large number of cardiac pathologies
including ischemic heart disease, idiopathic dilated cardiomyopathy,
hypertrophic cardiomyopathy, and cardiomyopathy of aging.  However,
strict causal relationships among abnormalities in mtDNA and/or
abnormalities in mitochondrial biogenesis and these cardiac
abnormalities are not fully elucidated.  Resolution of this problem
can come from study of animal models, which have not yet been
developed.  Such models will also provide the opportunity to test
potential therapeutic strategies, including the development of
mitochondrial gene therapy.
 
Some studies suggest that abnormalities in mtDNA not only cause the
rare but devastating syndromes that have been identified as
mitochondrial diseases, but contribute to the pathophysiology of
other widely prevalent diseases.  A deficiency of mtDNA has been
observed in HIV-infected patients treated with antiviral nucleoside
analogues (ANA), and is proposed to contribute to myopathic symptoms
in these individuals.  Evidence suggests that short-term usage of ANA
drugs is relatively safe; however, long term usage reveals that they
can become toxic and affect oxidative phosphorylation, which appears
to be attributable to a defect in mitochondrial replication.  This
defect resembles certain mitochondrial genetic diseases that have
been associated with cardiomyopathy, mitochondrial myopathy,
neuropathy, lactic acidosis, exocrine pancreas failure, pancreas
failure, liver failure and bone marrow failure.  It has been
suggested that mitochondrial toxic ANAs may serve as experimental
tools to clarify mtDNA replication.
 
In the area of hematology, evidence for the association of
mitochondrial DNA mutations and blood diseases is fragmentary.  One
exception is Pearson's syndrome, a progressive congenital disorder
involving the hematopoietic system, exocrine pancreas, liver and
kidneys.  Within the blood, it is characterized by bone marrow
failure, hypoproliferative sideroblastic anemia, and pancytopenia. It
is associated with enzymatic deficiencies in some of the respiratory
chain enzymes within blood cells that occur in conjunction with
large-scale, single deletions of the mitochondrial genes encoding
these enzymes.  This is the first reported mitochondriopathy with a
non-neuromuscular expression.  The reported abnormalities of both
erythroid and myeloid precursors in the arrow of Pearson's Syndrome
patients suggests a potential role of mtDNA in hematopoiesis.
 
Although Pearson's syndrome itself is relatively rare, it is
certainly possible that other forms of sideroblastic or aplastic
anemias may also be associated with acquired or inherited mtDNA
mutations.  Sideroblastic anemias in general have the unique
characteristic of amorphous iron deposits in erythroblast
mitochondria.  The role of iron in mitochondria and the ineffective
erythropoiesis in these anemias needs further study.  Iron in red
cell membranes has been reported in thalassemia and sickle cell
disease.  This iron deposition causes significant oxidation of
membrane proteins in these disorders, but little has been reported on
possible oxidative damage to mitochondria in the red blood cell
precursors.  In addition, little is known about possible
mitochondrial damage in other diseases involving iron overload or in
the blood of individuals undergoing chronic transfusion.
 
Many dysfunctions of electron transport chain enzymes as well as
mutant mtDNA have also been found in platelets and/or lymphocytes of
patients with diseases associated with aging, including Parkinson's,
Huntington's, and Alzheimer's diseases.  Furthermore, this phenomenon
has been reported in Down syndrome, which is characterized by an
accelerated aging process.  Some of these enzymatic dysfunctions have
been linked to mutations in mitochondrial genes encoding these
proteins.  Most of these mutations have been discovered as a result
of using blood cells because of their accessibility as a "diagnostic
test" to screen for mutations that may also occur in tissues more
directly involved in the disease, but are less accessible, such as
brain tissue from Parkinson's Disease patients.  It is quite possible
that the function of the blood cells themselves may be affected by
the mtDNA mutations.  Elucidating how the bioenergetic defects in
blood cells affect their own function may have implications for other
diseases involving mtDNA mutations.
 
The role of mutations in mtDNA in etiology and pathogenesis of lung
disease is virtually unexplored.  The lung might be particularly
prone to mitochondrial DNA damage as a result of its oxidative
environment, rapidly turning over epithelium, and constant exposure
to environmental agents. The consequences on mtDNA of exposure of
potential therapeutic agents such as nitric oxide are not understood.
Damage or loss of specific mitochondrial genes associated with energy
generation could potentially affect many aspects of pulmonary cell
function, particularly under stressful conditions.  Examples of lung
cell functions that might be impaired include surfactant and
extracellular matrix biosynthesis, cell repair processes, mucociliary
transport, ion gradients, and neural control of airway smooth muscle
function.  Thus, one objective of future research should be to
establish whether mtDNA damage occurs in the lung in association with
disease states, and if so, to determine the role of mtDNA damage and
repair in the etiology of lung disease.
 
Although much of the evidence involving a link between mtDNA
mutations and certain diseases is unequivocal, there is still a
compelling need to determine the extent to which mtDNA mutations
affect the natural history of heart, blood vessels, blood, and lung
diseases.  There have been few epidemiological studies of
mitochondrial disorders and thus the extent of the problem in general
populations is unknown. The attributable risk of myocardial,
hypertensive, and other cardiovascular diseases due to mitochondrial
gene mutations is also unknown.  The lack of an easy screening test,
other than the blood cell diagnostic test' mentioned above, which may
miss certain types of mtDNA mutations, has hampered this research.
However, maternal transmission of inherited mtDNA defects and the
apparent mendelian pattern of inheritance for certain mtDNA deletions
(implying nuclear gene involvement in mtDNA replication) suggests
that pedigree studies could be informative.  Family studies could be
used to elucidate susceptibility markers and factors associated with
phenotypic expression of mtDNA diseases.  Preexisting population
studies that have already collected DNA could assess mitochondrial
DNA variation in a relatively cost-effective manner.
 
Research Goals and Scope
 
The following examples of potential research projects are given for
illustrative purposes only and are not intended to define the scope
of relevant topics.  Investigators are expected to use their expert
knowledge of the field in developing responses to this initiative
 
o Establish animal and cellular models of mutant mtDNA relevant to
heart, vascular, lung and blood disorders
 
o Identify genes important for mtDNA replication or repair,
segregation of mitochondrial genomes during cell division, and
control of mtDNA copy numbers in cell types found in heart, vascular,
lung and blood disorders
 
o Develop methods to transfer exogenous genes into mammalian
mitochondria or to complement mitochondrial gene defects by gene
transfer to the nucleus of cardiovascular, lung and blood cells.
 
o Establish mechanisms of damage in relationship to the etiology of
the heart, vascular, lung and blood disease states in animals or
humans
 
o Elucidate mechanisms that promote mitochondrial DNA mutations in
ischemic heart disease and hyperoxic lung disease.
 
o Elucidate the role of mtDNA damage in early development of
cardiovascular, lung and blood cells
 
o Identify markers for susceptibility to mitochondrial diseases of
heart, vascular, lung and blood and development of preventive
strategies
 
o Elucidate the reasons that some mitochondrial mutations and
deletions give rise to clinically different heart, vascular, lung and
blood disorders and some have no effect.
 
o Elucidate quantitative relationships between mutant forms of mtDNA
and heart and lung dysfunction.
 
o Define the pathways for ATP synthesis and utilization changes in
blood cells, cardiovascular, and lung tissues with defective
mitochondrial genes.
 
o Identify mtDNA determinants of heart, vascular, lung, and blood
disease and risk factors.
 
o Define the pathways for ATP synthesis and utilization changes in
blood cells, cardiovascular and lung tissues with defective genes.
 
SPECIAL REQUIREMENTS
 
Upon initiation of the program, the NHLBI will sponsor periodic
meetings to encourage exchange of information among investigators who
participate in this program.  In the budget for the grant
application, applicants should request travel funds for a 1-day
meeting each year, most likely to be held in Bethesda, Maryland.
Applicants should also include a statement in their applications
indicating their willingness to participate in these meetings.
 
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN
SUBJECTS
 
It is the policy of the NIH that women and members of minority groups
and their subpopulations must be included in all NIH supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
that inclusion is inappropriate with respect to the health of the
subjects or the purpose of the research.  This new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines For Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
 
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
 
LETTER OF INTENT
 
Prospective applicants are asked to submit, by January 24, 1997, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating
institutions, and the number and title of the RFA in response to
which the application may be submitted.  Although a letter of intent
is not required, is not binding, and does not enter into the review
of a subsequent application, the information that it contains allows
NIH staff to estimate the potential review workload and avoid
conflict of interest in the review.  A faxed letter of intent may be
used in place of a posted one.
 
The letter of intent is to be sent to:
 
Dr. C. James Scheirer
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7220, MSC 7924
Bethesda, MD  20892-7924
Telephone:  (301) 435-0266
FAX:  (301) 480-3541
Email:  James_Scheirer@NIH.GOV
 
APPLICATION PROCEDURES
 
The research grant application form PHS-398 (rev. 5/95) is to be used
in applying for these grants.  Applications kits are available at
most institutional offices of sponsored research; from the Grants
Information Office, Office of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC
7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email:
ASKNIH@odrockm1.od.nih.gov; and from NHLBI program staff listed under
INQUIRIES.
 
The RFA label available in the application kit must be affixed to the
bottom of the face page.  Failure to use this label could result in
delayed processing of the application such that it may not reach the
review committee in time for review.  In addition, the title of the
application and the RFA number must be typed on line 2 of the face
page of the application form.
 
Submit a signed, typewritten original of the application, including
the Checklist, and three signed, exact photocopies in one package to
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, SUITE 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)
 
Submit an additional two copies of the application to Dr. Scheirer at
the address listed under LETTER OF INTENT.  It is important to send
these two copies at the same time as the original and three copies
are sent to the Division of Research Grants; otherwise, the NHLBI
cannot guarantee that the application will be reviewed in competition
for this RFA.
 
Sample budgets and justification page will be provided upon request
or following the submission of a letter of intent.
 
BUDGET INSTRUCTIONS The total direct costs must be requested in
accordance with the program guidelines and the modifications made to
the standard PHS 398 application instructions described below:
 
o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD Do not complete Form
Page 4 of the PHS 398 (rev 5/95).  It is not required nor will it be
accepted at the time of application.
 
o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT Do not complete
the categorical budget tables on Form page 5 of the PHS 398 (rev.
5/95).  Only the requested total direct costs line for each year must
be completed based on the number of $25,000 modules being requested.
Applicants may not request a change in the amount of each module.  A
maximum of seven modules ($175,000 direct costs) per year may be
requested and each applicant may request up to four years of support
for this RFA.  Direct cost budgets will remain constant throughout
the life of the project (i.e. the same number of modules requested
for all budget periods).  Any necessary escalation should be
considered when determining the number of modules to be requested.
However, in the event that the number of modules requested must
change in any future year due to the nature of the research proposed,
appropriate justification must be provided.  Total Direct Costs for
the Entire Proposed Project Period should be shown in the box
provided.
 
o BUDGET JUSTIFICATION
 
Budget justifications should be provided under "Justifications" on
Form Page 5 of the PHS 398.
 
List the names, role on the project and proposed percent effort for
all project personnel (salaried or unsalaried)and provide a narrative
justification for each person based on his/her role on the project.
 
Identify all consultants by name and organizational affiliation and
describe the services to be performed.
 
Provide a general narrative justification for individual categories
(equipment, supplies, etc.) required to complete the work proposed.
More detailed justifications should be provided for high cost items.
Any large one-time purchases, such as large equipment requests, must
be accommodated within these limits.
 
o CONSORTIUM/CONTRACTUAL COSTS - If collaborations or subcontracts
are involved that require transfer of funds from the grantee to other
institutions, it is necessary to establish formal subcontract
agreements with each collaborating institution.  A letter of intent
from each collaborating institution should be submitted with the
application.  Only the percentage of the consortium/contractual TOTAL
COSTS (direct and indirect) relative to the total DIRECT COSTS of the
overall project needs to be stated at this time.  The following
example should be used to indicate the percentage cost of the
consortium, "The consortium agreement represents 27% of overall
$175,000 direct costs requested in the first year.". A budget
justification for the consortium should be provided as described in
the "Budget Justification" section above (no Form Page 5 required for
the consortium).  Please indicate whether the consortium will be in
place for the entire project period and identify any future year
changes in the percentage relative to the parent grant.
 
If there is a possibility for an award, the applicant will be
requested to identify actual direct and indirect costs for all years
of the consortium.  Please note that total subcontract costs need not
be calculated in $25,000 modules. However, when subcontract funds are
added to the parent grant budget, the total direct cost amount must
be included in the number of $25,000 modules requested.
 
o BIOGRAPHICAL SKETCH - A biographical sketch is required for all key
personnel, following the modified instructions below.  Do not exceed
the two-page limit for each person.
 
Complete the educational block at the top of the form page;
 
List current position(s) and those previous positions directly
relevant to the application;
 
List selected peer-reviewed publications directly relevant to the
proposed project, with full citation;
 
The applicant has the option to provide information on research
projects completed and/or research grants participated in during the
last five years that are relevant to the proposed project.
 
o OTHER SUPPORT - Do not complete the "Other Support" pages (Form
Page 7).  Selected other support information relevant to the proposed
research may be included in the Biographical Sketch as indicated
above.  Complete Other Support information will be requested by NHLBI
staff if there is a possibility for an award.
 
o CHECKLIST - No "Checklist" page is required as part of the initial
application.  A completed Checklist will be requested by NHLBI staff
if there is a possibility for an award.
 
o The applicant should provide the name and phone number of the
individual to contact concerning fiscal and administrative issues if
additional information is necessary following the initial review.
 
Applications not conforming to these guidelines will be considered
unresponsive to this RFA and will be returned without further review.
 
Applications must be received by March 12, 1997.  If an application
is received after that date, it will be returned to the applicant
without review.  The Division of Research Grants (DRG) will not
accept any application in response to this RFA that is essentially
the same as one currently pending initial review, unless the
applicant withdraws the pending application.  The DRG will not accept
any application that is essentially the same as one already reviewed.
This does not preclude the submission of substantial revisions of
applications already re-viewed, but such applications must include an
introduction addressing the previous critique.
 
REVIEW CONSIDERATIONS
 
Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit by an appropriate
peer-review group convened by the NHLBI in accordance with NIH
peer-review procedures.  As part of the initial merit review, all
applications will receive a written critique and undergo a process in
which only those applications deemed to have the highest scientific
merit, generally the top half of applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the National Heart, Lung, and Blood Advisory Council.
 
The personnel category will be reviewed for appropriate staffing
based on the requested percent effort.  The direct costs budget
request will be reviewed for consistency with the proposed methods
and specific aims.  Any budgetary adjustments recommended by the
reviewers will be in $25,000. The duration of support will be
reviewed to determine if it is appropriate to ensure successful
completion of the recommended scope of the project.  Other review
criteria will include:
 
o scientific, technical or medical significance and originality of
proposed research
 
o appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research
 
o qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research
 
o availability of the resources necessary to perform the research.
 
o  adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
evaluated.
 
The initial review group will also examine the provisions for the
protection of human and animal subjects and the safety of the
research environment.
 
AWARD CRITERIA
 
Applications will compete for available funds with all other approved
applications.  The following will be considered in making funding
decisions:  quality of the proposed project as determined by
peer-review, availability of funds, and program priority.
 
INQUIRIES
 
Inquiries concerning this RFA are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
 
Direct inquiries regarding programmatic issues to:
 
Dr. Isabella Liang
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 9142, MSC 7940
Bethesda, MD  20892-7940
Telephone:  (301) 435-0520
FAX:  (301) 480-1335
Email:  liangi@gwgate.nhlbi.nih.gov
 
Dr. Carol Letendre
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10162, MSC 7950
Bethesda, MD  20892-7950
Telephone:  (301) 435-0080
FAX:  (301) 480-0867
Email:  letendrc@gwgate.nhlbi.nih.gov
 
Dr. Dorothy Gail
Division of Lung Diseases
National Heart, Lung, and Blood Institute
Two Rockledge Center, Suite 10100
6701 Rockledge Drive, MSC 7952
Bethesda, MD  20892-7952
Telephone:  301-435-0222
Fax:  301-480-3557
Email: gaild@gwgate.nhlbi.nih.gov
 
Ms. Phyliss Sholinsky
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
Two Rockledge Center, Suite 8151
6701 Rockledge Drive, MSC 7934
Bethesda, MD  20892-7934
Telephone:  301-435-0701
Fax:  301-480-1667
Email: sholinsp@gwgate.nhlbi.nih.gov
 
Direct inquiries regarding fiscal matters and requests for sample
budgets to:
 
Ms. Marie Willett
Grants Operations Branch
National Heart, Lung, and Blood Institute
Two Rockledge Center, Suite 7128
6701 Rockledge Drive, MSC 7926
Bethesda, MD  20892-7926
Phone:  301-435-0144
Fax:  301-480-3310
E-mail: willettm@gwgate.nhlbi.nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.837, 93.838, and 93.839.  Awards are made under
authorization of the Public Health Service Act, Title IV, Part A
(Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and
285) and administered under PHS grants' policies and Federal
Regulations 42 CFR 52 and 45 CFR Part 74.  This program is not
subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.
 
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-use of all tobacco
products.  In addition, Public Law 103-227, the Pro-Children Act of
1994, prohibits smoking in certain facilities (or in some cases, any
portion of a facility) in which regular or routine education,
library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS
mission to protect and advance the physical and mental health of the
American people.
 
.

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