Release Date:  August 24, 2000

RFA:  HL-01-001

National Heart, Lung, and Blood Institute
National Institute of Diabetes and Digestive and Kidney Diseases

Letter of Intent Receipt Date:  January 18, 2001
Application Receipt Date:       February 20, 2001


The objectives of this initiative are to stimulate research to identify and 
characterize the modifier genes responsible for variation in clinical 
progression and outcome of heart, lung and blood diseases due to single gene 
defects.  Identification of the genes responsible for these differences would 
lead to better understanding of disease pathogenesis, early diagnosis, and 
improved treatment.  


The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of "Healthy People 2010," a PHS-led national 
activity for setting priority areas.  This Request for Applications (RFA), 
"Genetic Modifiers of Single Gene Defect Diseases," is related to one or more 
of the priority areas.  Potential applicants may obtain a copy of "Healthy 
People 2010" at


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 or local governments, and eligible 
agencies of the Federal government.  Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as Principal 


This RFA will use the National Institutes of Health (NIH) research project 
grant (R01) award mechanism.  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 that is received in response to this 
RFA may not exceed five 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.  The anticipated award date is September 30, 2001.

Applicants from institutions that have a General Clinical Research Center 
(GCRC) funded by the NIH National Center for Research Resources may wish to 
identify the GCRC as a resource for conducting the proposed research.  If so, 
a letter of agreement either from the GCRC program director or principal 
investigator should be included with the application.


The National Heart, Lung, and Blood Institute (NHLBI) intends to commit 
approximately $10,000,000 total costs and National Institute of Diabetes and 
Digestive and Kidney Diseases (NIDDK) intends to commit approximately 
$1,000,000 total costs in FY 2001 to fund up to18 new grants in response to 
this RFA.  An application may request a project period of up to five years.  
It is expected that applications will not exceed a budget of $500,000 in 
direct costs, excluding Facilities and Administrative costs on consortium 
arrangements, in the first year.  Applications exceeding this budget cap must 
be appropriately justified.  Annual increases in non-competing years are not 
allowed.  Because the nature and scope of the research proposed may vary, it 
is anticipated that the size of each award will also vary.  Although the 
financial plans of the NHLBI and NIDDK provide support for this program, 
awards pursuant to this RFA are contingent upon the availability of funds and 
the receipt of a sufficient number of applications of appropriate scientific 
and technical merit.



All diseases are variable in their presentation due to differences in the 
genetic makeup and the environmental exposure of the affected individual.  For 
disorders inherited in a Mendelian fashion, a single gene plays the 
predominant role in the development of a disease phenotype.  However, 
phenotype variation occurs even among those who have identical genotypes at a 
disease locus.   To further our understanding of the molecular basis of 
monogenic disorders, it will be necessary to find other genes that contribute 
to phenotype variability.

There are a number of heart, lung and blood disorders that are primarily due 
to alterations in a single gene.  Examples include cystic fibrosis, alpha-1-
antitrypsin deficiency, sickle cell disease, thalassemia, hemochromatosis, 
hemophilia, glucocorticoid remediable aldosteronism (GRA), Liddle=s Syndrome 
and other hypertensive conditions, as well as cardiac myopathies, dysplasias, 
and arrhythmias that result in Sudden Cardiac Death.  Although individuals may 
have single gene defects, there can be tremendous variation in the 
progression, complications and outcome of the disease (even in an extended 
family) that may be due to the interaction of the disease gene with other 
genes, impacting on the final disease presentation.

Defects in a single gene for cystic fibrosis transmembrane conductance 
regulator (CFTR) give rise to the disorder of CF, the nation’s number one 
genetic killer of children and young adults.  A single nucleotide defect in 
the coding sequence gives rise to alpha-1-antitrypsin deficiency (AATD).  
However, increasing evidence suggests that these genes do not function alone 
in determining disease outcome.  The severity of pulmonary disease can vary 
greatly among individuals, even with the identical mutations.  Evidence 
suggests that this variation is due to the interaction of disease gene with 
other genes, impacting on the final disease presentation.  Yet, relatively 
little is known about the identity of these genes and how other genes, 
distinct from the disease locus, modify the major gene involved in CF and 
AATD. The lack of a close correlation between the genotype and severity of 
pulmonary disease suggests that genetic determinants independent of the 
disease play a significant role in the development of the lung disease.  
Small-scale family studies of CF and AATD support the existence of modifiers 
for lung disease in humans.  However, specific loci have not yet been 
identified.  For CF, recent exploration of a potential candidate gene involved 
in the inflammatory and immune responses of the lung, e.g., mannose-binding 
lectin (MBL), showed a striking correlation between genetic variants that 
reduce the amount of this lectin and lung function in CF patients chronically 
infected with P. aeruginosa, survival rates, and median life expectancy among 
CF patients grouped according to MBL serum levels.  A modifier gene for 
meconium ileus in CF has been localized to chromosome 19 and several candidate 
genes are being studied.  Other manifestations of CF such as pancreatic 
insufficiency and degree of wasting may also be influenced by modifier genes. 
For AATD, evidence exists that co-inherited defects in the endoplasmic 
reticulum degradation make certain individuals susceptible to the development 
of the liver disease found in 12 to15 percent of AATD patients.  These results 
confirm that genetic modifiers exist, and can be identified using current 

Sickle cell disease (SCD) is the earliest described and arguably best 
characterized disease at the molecular level. However, what is not well 
understood is the marked variability of the clinical manifestations. The 
clinical picture in some patients may be a devastating course of acute and 
chronic events, resulting in severe end organ damage, including pulmonary 
complications and stroke. However, in other patients, the disease may present 
with a relatively mild clinical phenotype and minimal morbidity.  The cause of 
these differences is unclear and cannot be explained by the substitution of 
valine for glutamic acid at position 6 in the beta-globin chain, the common 
molecular link among all patients. A priori, both genetic and nongenetic 
factors are likely to modulate the severity of SCD, but the genetic factors 
are more amenable to study. There have been two case reports of undefined, 
non-genetic factors affecting the course of SCD in identical twins; however, a 
large twin study has not yet been done. On the genetic side, statistically 
significant correlations have been reported between beta-globin gene cluster 
polymorphisms (haplotypes), or co-inheritance of alpha-thalassemia, and SCD 
morbidity. Further support for the existence of genetic modifiers of SCD 
severity has come from investigations of various additional genetic factors, 
but especially those which determine fetal hemoglobin (Hb F) levels.  In 
addition to this evidence for indirect genetic modifiers associated with Hb F 
levels, recent studies in progress have implicated other genetic factors, 
including polymorphisms in HLA genes related to stroke, and in MTHFR (5,10-
methylene-tetrahydrofolate reductase) genes related to avascular necrosis.  
Thus, both genetic and non-genetic modifiers of SCD have been reported, and 
the relative importance of the two is presently unclear.  However, if 
additional genetic modifiers could be identified with certainty, their ability 
to predict benign versus severe disease would clearly improve patient care.

Hemochromatosis is a common inherited disease of iron overload that results 
from mutations in the HFE gene. Increased iron storage, particularly in the 
liver, leads to the clinical course of the disease, but the iron accumulation 
and the associated clinical presentation can be highly variable, even within 
one family.  A recent population study found that only half of those who were 
homozygous for the major HFE mutation had clinical features of 
hemochromatosis, and others have reported an even smaller proportion of 
affected individuals with clinical signs of the disease. It appears most 
likely that genetic factors are involved in modifying the expression of the 
gene, although some environmental factors may have a role. Examples in 
Mediterranean populations of iron overload in which HFE coding sequences are 
normal indicate that genes other than HFE and/or HFE mutations may be 
responsible. A single mutation (C282Y) in HFE has been found to be responsible 
for the vast majority of clinical disease, so mutations in other genes must be 
involved, resulting in differences in iron loading. There is recent clinical 
evidence for hemochromatosis-modifying genes, but the identity of these genes 
is not known. The obvious candidate genes are those encoding proteins known to 
be important in iron transport, but it is not known to what degree variations 
in the iron transport genes contribute to the clinical presentation of 
hemochromatosis and other iron disorders. Although several important genes of 
iron transport have been identified in recent years, there may be others not 
yet discovered that impact on the expression of the HFE gene. 
Reportedly “monogenic” cardiovascular disorders (such as inheritable forms of 
hypertension, dilated and hypertrophic cardiomyopathies, arrhythmogenic 
dysplasias, atrial arrhythmias, and arrhythmias that contribute to Sudden 
Cardiac Death), show large differences in phenotypic expression and 
penetrance.  Such conditions affect thousands of cardiac patients as well as 
many apparently asymptomatic individuals.  In the case of mutations associated 
with familial hypertension, many of the primary defects occur in genes 
involved in the regulation of renal Na transport and in its hormonal 
regulators (aldosterone, vasopressin, angiotensin, etc.).  Modifying factors 
or genes that define vulnerability to the primary defect in these conditions 
may be particularly important in mediating end-organ injury.  Similarly, many 
of the genetically variable forms of hypertrophic and dilated cardiomyopathies 
are associated with primary defects in at least eight different genes which 
code for sarcomeric contractile proteins, but modifier genes alter clinical 
outcome here as well.  Although the genes for arrhythmogenic dysplasia and 
atrial arrhythmias have not been identified, many of those cases that map to 
single chromosomal sites have widely disparate degrees of penetrance.  
Hundreds of mutations in the coding regions for at least six genes determining 
structural subunits for Na and K ion channels have been implicated in causing 
inherited ventricular arrhythmias, such as the congenital Long QT Syndromes, 
and the impact of many of these on channel function has been examined at a 
molecular level and in transgenic mice.  Despite functional similarity at 
these levels, there is considerable divergence in how these mutations affect 
in vivo cardiac electrophysiology in affected individuals within the same 
family, and differing degrees of penetrance between different affected 
families with the same identical mutation.  For example, different mutations 
within the same exon and domain of one gene (i.e., the SCN5A Na channel alpha 
subunit), have been linked to three quite distinct cardiac disorders (i.e., 
LQT-3 Syndrome, idiopathic ventricular fibrillation and primary cardiac 
conduction disease or Lev’s syndrome), each of which results in a different 
electrical phenotype.  This degree of allelic and genetic heterogeneity is 
likely to involve a number of as yet unidentified genetic and environmental 
modifiers and interactions (e.g., in pathways of autonomic renal control), 
subject to independent variation.

The genes responsible for a variety of inherited heart, lung and blood 
disorders have been identified using functional and positional approaches.  
Now the difficult process of finding the modifier genes and their relevant 
mutations must be undertaken. The number of biologically plausible candidate 
genes may be very large.  As such, the search for genetic modifiers of 
Mendelian disorders will be similar to studies of complex genetic disorders 
such as asthma or hypertension.  Association studies utilizing reasonable 
candidate genes or candidate loci offer valuable approaches to facilitate 
efforts to find the genes.  The completion of the human genome project and the 
development of high-throughput technologies such as "gene chip" and 
streamlined SNP (single nucleotide polymorphism) analyses should greatly 
facilitate the search for genes that contribute to disease variability.  The 
identification and characterization of modifier genes will clarify the process 
of pathophysiology, enable more accurate prognosis, early diagnosis, and may 
provide novel, and possibly, more accessible therapeutic targets, that are 
more useful than the gene primarily involved in causing the disease.

Research Scope

This initiative is intended to solicit applications to identify the modifier 
gene or genes responsible for variation in the clinical progression and 
outcome of heart, lung, and blood diseases known to be due to single gene 
defects (using state-of-the-art approaches including, but not limited to, 
genetic mapping, positional candidate cloning, positional cloning to narrow 
the region, computer cloning, and genomic technologies), to characterize the 
allelic variants of the gene(s) identified, and to demonstrate that the 
variation in the gene(s) is responsible for phenotype variation. Applicants 
must be able to demonstrate the availability of well-characterized families 
and/or well-defined genetic animal models of single gene disorders in whom 
some aspect of phenotype variability has been demonstrated to be inherited 
independent of the disease-causing gene.
Some research topics that will be responsive to this program are listed below. 
These are only examples; applicants are encouraged to propose other topics 
that address the overall goals of this initiative.

The following are examples of research areas relevant to the objectives of 
this RFA:
o Loci containing a modifier gene or genes have been mapped to multiple 
regions of  the genomes of humans and animal models.  Studies are now needed 
to identify specific polymorphisms in candidate genes that lie within these 
linkage regions.  Although it will likely be prudent to begin examining 
intuitive candidates within linkage regions, this approach can greatly bias 
the results and potentially lead to exclusion of important genes.  Thus 
investigators should consider combining new high throughput technologies such 
as "gene chip" approaches and rapid SNP analyses with the more traditional 
approaches.  Recent advances in molecular techniques such as "gene chip 
technology" have provided considerable power and speed in identification of 
differentially expressed genes.  Functional genomic approaches (using cDNA and 
oligonucleotide arrays) to identify differentially expressed genes, combined 
with classic genetic analysis and positional candidate approaches, can 
significantly enhance gene discovery efforts. 

o A variety of animal models have advanced our understanding of the 
pathogenesis of single gene disorders.  As genetic studies of animal models 
have yielded important insight into the mechanisms underlying these disease 
states, it is likely that they will be equally useful in the identification 
and characterization of modifier genes.  Numerous murine strains, with well-
defined genomes that exhibit a high degree of homology with the human genome, 
have considerable potential to provide insights into the presence and location 
of modifier genes.  Thus, studies that explore the genetic basis of phenotype 
variation in animal models of monogenic human diseases are needed.
o Identification of genetic modifiers in humans can be facilitated by detailed 
study of genetically related individuals.  Analysis of concordant and 
discordant traits among affected family members can point to genetically 
determined aspects of phenotype variability.  Studies of this type require the 
collection and characterization of sufficient numbers to afford statistical 
power.  Thus, collaborative arrangements that facilitate the formation or 
extension of patient registries for the purpose of modifier gene 
identification are needed.
o Variation in proteins involved in molecular pathways affected by the 
dysfunction of a disease-causing gene are likely to influence pathogenesis.  
Critical members of a particular pathway may be excellent candidate modifier 
genes.  The identification of naturally occurring and biologically relevant 
variants in these candidates, and demonstration of their contribution to 
alteration in pathways affected in a monogenic disease would support their 
candidacy as modifier genes. Thus, in addition to human studies, in vitro 
and/or animal studies could be used to explore the functional contribution of 
various candidate genes to phenotype variation in monogenic disorders.
o Even in the case of monogenic diseases, evidence suggests that the 
interactions of multiple genes result in expression of specific disease 
traits. Once polymorphisms relevant to phenotype have been identified in a 
modifier gene or genes, efforts should be directed at assessing interactions 
between the disease-causing gene and the modifiers.
o Genotype/phenotype studies reveal the degree to which disease severity can 
be attributed to allelic differences.  In certain monogenic disorders, the 
strength of the correlation between presentation and mutation varies by organ 
system, suggesting that gene-environment interactions may play a significant 
role in predisposition to this disease.  Thus, studies to assess these gene-
environment interactions are also needed.


To be responsive to this RFA, applications must demonstrate the availability 
of well-characterized families and/or well-defined animal models with a 
monogenic disorder where the correlation between genotype at the disease locus 
and phenotype has been explored in depth.  Studies of the genetic basis of 
phenotype variation in animal models are responsive to this RFA; however, 
applicants who propose to conduct genetic studies using animal models must 
demonstrate their usefulness in gaining insights into modifiers of the human 
phenotype.  Additional studies designed to extend and validate findings in 
human disorders are particularly encouraged.  Human studies are especially 
solicited, but must be designed with sufficient statistical power to address 
the hypothesis being tested.  The use of existing registries and /or 
repositories of biological samples from well-characterized patients is 
encouraged.  Applicants wishing to pursue studies related to rare diseases are 
encouraged to form consortium arrangements with collaborating institutions, in 
order to have adequate statistical power for their studies.  Focused clinical 
and epidemiologic studies that address a specific aspect of phenotype 
variability, and facilitate the identification of modifier genes of Mendelian 
disorders relevant to heart, lung, and blood diseases, are within the scope of 
this RFA.  
Upon initiation of the program, the NHLBI will sponsor periodic meetings to 
encourage exchange of information among investigators who participate in this 
program.  This is especially critical if more than one group focuses on the 
same patient population or animal models to avoid unnecessary duplication and 
to expedite modifier gene discovery efforts.  Travel funds should be included 
in the modules for two people (the Principal Investigator and one co-
investigator from the grant) to attend a one day meeting two times each year, 
most likely to be held in Bethesda, Maryland.  Applicants should also include 
a statement in their application indicating their willingness to participate 
in these meetings and to interact openly with other study participants in 
sharing genetic approaches/strategies and findings among awardees so as to 
provide the greatest promise for scientific advances from the approved 
research scope of the awards.


It is the policy of the NIH that women and members of minority groups and 
their sub-populations must be included in all NIH-supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale and justification are provided indicating that inclusion 
is inappropriate with respect to the health of the subjects or the purpose of 
the research.  This policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law 103-43). 

All investigators proposing research involving human subjects should read the 
UPDATED "NIH Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research," published in the NIH Guide for Grants and Contracts on 
August 2, 2000 
a complete copy of the updated Guidelines are available at  The 
revisions relate to NIH defined Phase III clinical trials and require: a) all 
applications or proposals and/or protocols to provide a description of plans 
to conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) all 
investigators to report accrual, and to conduct and report analyses, as 
appropriate, by sex/gender and/or racial/ethnic group differences.


It is the policy of the NIH that children (i.e., individuals under the age of 
21) must be included in all human subjects research, conducted or supported by 
the NIH, unless there are scientific and ethical reasons not to include them. 
This policy applies to all initial (Type 1) applications submitted for receipt 
dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
"NIH Policy and Guidelines on the Inclusion of Children as Participants in 
Research Involving Human Subjects" that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.


All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.


Prospective applicants are asked to submit 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 
subsequent applications, the information that it contains allows NHLBI staff 
to estimate the potential review workload and plan the review.  

The letter of intent is to be faxed or mailed to Dr. Deborah Beebe at the 
address listed under INQUIRIES by January 18, 2001.


The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  These forms are available at most institutional 
offices of sponsored research and from the Division of Extramural Outreach and 
Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 
7910, Bethesda, MD 20892-7910, telephone 301/710-0267,

The RFA label found in the PHS 398 (rev. 4/98) application form must be affixed 
to the bottom of the face page of the application.  Type the RFA number on the 
label.  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 RFA title and number must be typed on line 2 of the face page 
of the application form and the YES box must be marked.  

The sample RFA label available at: has been modified to 
allow for this change.  Please note this is in pdf format.

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed, photocopies, in one package to:


BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application must be sent 
to Dr. Deborah Beebe at the listing under INQUIRIES. 

Applications must be received by the application receipt date listed in the 
heading of this RFA.  If an application is received after that date, it will be 
returned to the applicant without review.

The Center for Scientific Review (CSR) 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 CSR 
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 reviewed, but such applications must include an 
introduction addressing the previous critique.


Upon receipt, applications will be reviewed for completeness by CSR and 
responsiveness by NHLBI.  Incomplete and/or non-responsive applications will be 
returned to the applicant without further consideration.

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 the review criteria stated below.  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 the 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 and/or the National 
Diabetes and Digestive and Kidney Diseases Advisory Council.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In the 
written comments, reviewers will be asked to discuss the following aspects of 
the application in order to judge the likelihood that the proposed research will 
have a substantial impact on the pursuit of these goals.  Each of these criteria 
will be addressed and considered in assigning the overall score, weighting them 
as appropriate for each application.  Note that the application does not need to 
be strong in all categories to be judged to have major scientific impact and 
thus deserve a high priority score. For example, an investigator may propose to 
carry out important work that by its nature is not innovative but is essential 
to move a field forward.

1) Significance.  Does this study address an important problem?  If the aims of 
the application are achieved, how will scientific knowledge be advanced?  What 
will be the effect of these studies on the concepts or methods that drive this 

2) Approach.  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?

3) Innovation.  Does the project employ novel concepts, approaches or method?  
Are the aims original and innovative?  Does the project challenge existing 
paradigms or develop new methodologies or technologies?

4) Investigator.  Is the investigator appropriately trained and well suited to 
carry out this work?  Is the work proposed appropriate to the experience level 
of the principal investigator and other researchers (if any)?

5) Environment.  Does the scientific environment in which the work will be done 
contribute to the probability of success?  Do the proposed experiments take 
advantage of unique features of the scientific environment or employ useful 
collaborative arrangements?  Is there evidence of institutional support?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o The adequacy of the research plans to include both genders, minorities and 
their subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 

o The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o The adequacy of the proposed protection for humans, animals or the 
environment, to the extent that may be adversely affected by the project 
proposed in the application.

The initial review group will also examine the provisions for the protection of 
human subjects and the safety of the research environment.

The personnel category will be reviewed for appropriate staffing based on the 
requested percent effort and justification provided.  The direct costs budget 
request will be reviewed for consistency with the proposed methods and specific 
aims.  The duration of support will be reviewed to determine if it is 
appropriate to ensure successful completion of the requested scope of the 


Letter of Intent Receipt Date:    January 18, 2001
Application Receipt Date:         February 20, 2001
Peer Review Date:                 June/July 2001
Council Review:                   September 6-7, 2001 
Earliest Anticipated Start Date:  September 30, 2001


Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)

o Availability of funds

o Programmatic priorities


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:


Susan Banks-Schlegel, Ph.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room10018, MSC 7952
Bethesda, Maryland 20892-7952
Telephone:  (301) 435-0202
FAX:  (301) 480-3557
E-mail: SchlegeS@

Extrapulmonary CF:

Catherine McKeon, Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd Room 6103, MSC 5460
Bethesda, Maryland 20892-5460
Telephone: (301) 594-8810
FAX: (301) 480-3503


Greg Evans, Ph.D.
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room10152, MSC 7950

Bethesda, Maryland 20892-7950
Telephone:  (301) 435-0055
FAX:  (301) 480-0868
E-mail: Evansg@

David G. Badman, Ph.D.
Division of Kidney, Urologic and Hematologic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd, Room 621, MSC 5458
Bethesda, Maryland 20892-5458
Telephone:(301) 594-7717
FAX: (301) 480-3510


Peter Spooner, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 9192, MSC 7940
Bethesda, Maryland 20892-7940
Telephone:  (301) 435-0504
FAX:  (301) 480-1454
E-mail: SpoonerP@

Direct inquiries regarding review matters and address the letter of intent to:

Deborah Beebe, Ph.D.
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room , MSC 7924
Bethesda, Maryland 20892-7924
Telephone: (301) 435-0270
FAX: (301) 480-3541

Direct inquiries regarding fiscal matters to:

Tanya McCoy
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7154, MSC 7926
Bethesda, MD 20892-7926
Telephone:  (301) 435-0171
FAX:  (301) 480-3310
E-mail: McCoyT@


This program is described in the Catalog of Federal Domestic Assistance, No. 
93.838, 93.847, and 93.849.  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 and 92.  This program is not 
subject to the intergovernmental review requirements of Executive Order 12372 or 
a Health Systems Agency Review.

The PHS strongly encourages all grant 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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