Full Text ES-97-001
NIH GUIDE, Volume 26, Number 4, February 7, 1997
RFA:  ES-97-001
P.T. 34

  Growth Factors 
  Environmental Effects 

National Institute of Environmental Health Sciences
Letter of Intent Receipt Date:  April 18, 1997
Application Receipt Date:  May 16, 1997
Historically, the elimination of toxic agents from the environment
has dominated the field of prevention.  Although the causes of
certain human diseases are known, explicit preventive strategies
still cannot be offered for avoidance of numerous risk factors
associated with many types of disease sequelae. Recently, control
strategies involving a more mechanistic approach derived from
chemical and biological research have received more emphasis. The
objective of the strategies is eventual intervention through
preventive/protection or other active means of modulating the risk
The National Institute of Environmental Health Sciences (NIEHS) has
posed as one of its major goals of the 1990s the development of an
effectual knowledge base that would equip clinicians to effectively
treat people who are affected adversely by exposure to environmental
agents.   The mechanistic knowledge of environmental agent impact on
the genome exists, either in actuality or conceptually; therefore,
through the coupling with recent advances in molecular biology, the
capability exists to intercede or modulate environmentally-induced
toxic effects.  Accordingly, the objective of this Request for
Applications (RFA) is to encourage innovative, mechanistically based
research to elucidate how growth factors modulate environmentally
induced altered gene functions; and conversely, how environmental
agents alter or modulate the function of growth factors and the
cellular signaling cascades.  Information derived from these studies
opens the possibility of developing therapeutic strategies to protect
normal tissues from environmental toxicants.
The NIEHS is the principal Federal funding agency that supports
research examining human health consequences of exposure to physical
and chemical toxicants in the environment.  Research supported by
NIEHS spans many disciplines, including toxicology, molecular and
cellular biology, epidemiology, and clinical research.
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 RFA,
"Modulation by Growth Factors and Signal Transduction Pathways of
Environmentally Induced Disease/Dysfunction" is related to the
priority area of 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
Superintended of Documents, Government Printing Office, Washington,
DC 20402-9325 (telephone:(202) 512-1800).
Applications may be submitted by domestic and foreign, for profit and
non-profit organizations, public and private, such as universities,
colleges, hospitals, laboratories, unit of State or local governments
and eligible agencies of the Federal government.  Applications from
minority individuals and women are encouraged.
This RFA will use the NIH individual 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 requested direct costs submitted in response to this
RFA may not exceed $200,000 per year.
This RFA is a one-time solicitation.
The total estimated funds available for the first year of support for
the entire program are expected to be $1,500,000 in fiscal year 1997.
 Although the actual  number may vary, the anticipated number of
awards is four to six.  The level of support is dependent on the
receipt of sufficient number of applications of high scientific
merit.  Although this program is provided for within the financial
plans of the NIEHS, awards pursuant to this RFA are contingent upon
the availability of funds for this purpose.
NIEHS has a continued commitment to stimulating research activities
in the area of molecular intervention.  Studies began in 1993 that
focused on the use of molecular biomarkers as intermediate markers or
endpoints to monitor the development, exacerbation or treatment of
environmentally-induced diseases in clinical studies.  These studies
included biomarkers of inflammation in lung disease patients
occupationally exposed to grain dust and endotoxins, immune markers
in environmentally-induced asthma, biomarkers of dioxin-related
compounds in humans and animals, molecular markers of response in
beryllium-induced lung disease, and the development of markers to be
used to measure success in interventional studies of lead in adults.
As the results from these and other studies unfold, they will begin
to have an impact on the Institute's research strategy to intervene
at the molecular level in environmentally induced
disease/dysfunction. Because of the diversity of this research area,
this is the second such announcement; its focus is on the modulation
of growth factors and by elements within signal transduction pathways
in environmentally-induced altered gene function/expression.
This RFA is part of a larger program, the "Molecular Interventions
for Environmentally-Induced Disease Prevention".  NIEHS's molecular
intervention initiative is an element of the basic research agenda
for Healthy People 2000, and is related to the national strategy for
significantly improving the health of the Nation during the current
This initiative is aimed at encouraging investigator-initiated
research to study basic molecular, biochemical, cellular, and
structural mechanisms in the modulation of environmentally induced
diseases or disorders.  It is anticipated that these investigations
will allow for innovative approaches in understanding the mechanism
of the xenobiotic-induced molecular alterations in specific target
cells and organs germaine to modulating gene expression, specifically
by growth factors and/or signal transduction pathways.  These studies
would undoubtedly contribute to the development of specific therapies
designed to amplify or decrease the susceptibility of individual cell
types to specific environmental agents, and could form the basis for
treatment of a variety of human diseases or disorders.  Collaborative
research efforts between investigators of the environmental health
research community and molecular and structural biologists, molecular
modeling scientists, and clinicians are especially encouraged.
It is widely recognized that the response to cell damage is highly
complex in its control and regulation, and includes direct
interactions of xenobiotics with extracellular components,
modulations of cell signaling pathways, transcriptional induction,
cell cycle arrest, and effects on DNA structure and function.
The following examples of research interest are not intended to be
complete, and investigators may study these and other topics that
meet the objectives of this RFA:
o  Studies targeted at determining how growth factors and their
receptors modulate environmentally-induced altered gene function and
o Studies aimed at understanding how cellular signaling pathways
modulate xenobiotic-induced gene expression;
o  Studies designed to improve our understanding of the correlation
between chemical induction or suppression of programmed cell death or
apoptosis, specifically as related to the use of this understanding
in the potential modulation of such actions;
o  Research aimed at gaining a better understanding of the molecular
and structural basis of tissue-specific and stage-specific gene
expression of growth factors and their receptors following xenobiotic
exposure, e.g., to identify and characterize factors that control
cell specificity of gene expression and to utilize these cell-
specific elements to explore the physiological consequences.
To be responsive to this RFA, investigators should be able to
illustrate how their proposed studies could contribute to the
development of therapeutic strategies to prevent or ameliorate
environmentally induced diseases or dysfunctions.
Annual meetings, to be held in Research Triangle Park, NC, are
planned for the exchange of information among investigators.
Applicants must budget travel costs associated with these meetings in
their applications.
Prospective applicants are asked to submit, by April 18, 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 consultants,
the 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 application, the information
that it contains is helpful in planning for the review of
applications. It allows NIEHS staff to estimate the potential review
work load and to avoid conflict of interest in the review.
The letter of intent is to be sent to:
Ethel B. Jackson, D.D.S.
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O.Box 12233
111 T. W. Alexander Drive, Building 17, Room 1716
Research Triangle Park, NC 27709
Telephone:  (919) 541-7826
FAX:  (919) 541-2503
Email:  jackson4@niehs.nih.gov
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 and may be obtained
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, email:
The RFA label available in the PHS 398 application form must be
affixed to the bottom of the face page of the application.  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.
Submit a signed, typewritten original of the application, including
the checklist, and three signed, clear , and single sided 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:
Ethel B. Jackson, D.D.S.
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O.Box 12233
111 T. W. Alexander Drive, Building 17, Room 1716
Research Triangle Park, NC 27709
Applications must be received by May 16, 1997.  If an application is
received after that date, the DRG may contact the applicant to
determine whether it will be returned to the applicant or be reviewed
with unsolicited applications for the next regular receipt date.  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 include
the submission of substantial revisions of applications already
reviewed, but such applications must include an introduction
addressing the previous critique.
The following is the schedule planned for this initiative.  It should
be noted that this schedule may be changed without notification due
to factors that were unanticipated at the time of the RFA.  Contact
the program official listed under INQUIRIES regarding any changes in
the schedule.
Letter of Intent Receipt Date:  April 18, 1997
Application Receipt Date:       May 16, 1997
Initial Scientific Review:      July 21-22, 1997
Advisory Council Review:        September 1997
Anticipated Date of Funding:    September 1997
Applications that are complete and responsive to this RFA will be
evaluated for scientific and technical merit by an appropriate peer
review group convened by the NIEHS 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 the applications under review, will be
discussed, assigned a priority score, and receive a second level
review by the National Environmental Health Sciences Advisory
Council. Applications considered non-responsive to the RFA will be
returned to the applicant for submission through the competitive
Review Criteria
The following criteria will be considered:
o  scientific, technical, or medical significance and originality of
the 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 key personnel;
o  availability of resources necessary to perform the research; and
o  appropriateness of the proposed budget and duration in relation to
the proposed research.
The anticipated date of award is September 1997.  The following will
be considered in making funding decisions:
o  quality of the proposed project as determined by peer review;
o  availability of funds; and
o  program balance among research areas of the announcement.
Written and telephone inquires concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcomed.
Direct inquiries regarding programmatic issues to:
Jose Velazquez, Ph.D.
Chemical Exposures and Molecular Biology Branch
National Institute of Environmental Health Sciences
P.O. Box 12233, 104 Alexander Drive, MD-3-04
Research Triangle Park, NC  27709
Telephone:  (919) 541-4998
FAX:  (919) 541-4937
Email:  velazqu1@niehs.nih.gov
Direct inquiries regarding fiscal matters to:
Mr. David L. Mineo
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233
Research Triangle Park, NC 27709
Telephone:  (919) 541-1373
This program is described in the Catalog of Federal Domestic
Assistance No.93.113, 93.114, and 93.15.  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, 43 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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