The goal of this Request for Applications (RFA) is to foster the development of research to advance our understanding of the pathogenesis of scleroderma and to promote the design, development and pilot testing of hypothesis-driven innovative therapeutic approaches. We encourage applications from scientists who have not previously worked on scleroderma, as well as those with substantial ongoing scleroderma-focused effort.

MISSION OF THE SCLERODERMA RESEARCH FOUNDATION
In its mission to find a cure for scleroderma, the Scleroderma Research Foundation seeks to advance research by: promoting collaboration and cross-institutional cooperation among scientists in a variety of disciplines; attracting promising new scientists to scleroderma research; maintaining scleroderma Centers of Excellence; and bringing new technology and thinking to the field of scleroderma research.

ELIGIBILITY REQUIREMENTS
Applications may be submitted by non-profit domestic or foreign organizations, public or private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Interested for-profit organizations should direct inquiries concerning eligibility to the SRF. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators.

MECHANISM OF SUPPORT
The mechanisms of support will include the Investigator-Initiated Research Grant (SRF01), the Exploratory/Developmental Research Grant (SRF02) and the New Faculty Grant (SRF03):

• Investigator-Initiated Research Grant (SRF01) provides support for a larger-scale project in scleroderma research to be performed by the named investigator(s) in an area representing his/her specific interest and competencies. Applicant(s) will be solely responsible for planning, directing, and executing the proposed project.


• Exploratory/Developmental Research Grant (SRF02) is for experienced researchers in scleroderma or other fields to take a cross-disciplinary approach toward scleroderma research in a smaller-scale project. Scientists may adapt proven technologies from other disciplines to advance our understanding of the pathogenesis of scleroderma. Investigators may also conduct small-scale clinical projects. They may gather pre-clinical data from new therapies or obtain preliminary data on toxicity and efficacy in a limited number of patients.
  
  Exploratory/developmental research grants are not intended to support large-scale undertakings or supplement ongoing research; instead, investigators are encouraged to use the grant to explore the feasibility of innovative research that would not qualify for an Investigator-Initiated Research Grant. Researchers can also use the Exploratory/Developmental Research Grant to develop a research basis for a subsequent Investigator-Initiator Research Grant or other funding. The specific aims of the Exploratory/Developmental Research Grant project may be incorporated into the application for the Investigator-Initiated Research Grant prior to the termination of the Exploratory/Developmental Research Grant.


• New Faculty Grant (SRF03) will enable the investigator to establish an independent program in scleroderma research while the candidate is beginning a tenure-track appointment at a public or private non-profit institution in the United States or abroad. To be eligible for the SRF03, the candidate must be in a tenure-track position, not held a previous tenure-track position, nor held the same tenure-track position for more than three years; and have demonstrated significant commitment to scleroderma research as a post-doctoral or clinical fellow. The candidate should be within seven years of receipt of her/his research or health professional doctoral degree as of the date of application.

Investigators proposing to conduct small, pilot/toxicity clinical trials are advised to review the NIAMS guidelines for preparation of clinical trial applications and the NIAMS guidelines for Data and Safety Monitoring Boards (http://www.nih.gov/niams).

FUNDING
The specific number of projects to be funded will depend on the merit and scope of the applications received and the availability of funds. Funding support from the SRF may not be used for administrative overhead, indirect expenses, or other institutional charges. Investigator-Initiated Research grants (SRF01) may not exceed $200,000 per year in total costs, and grants spanning up to three (3) years will be considered.

Exploratory/Developmental grants (SRF02) may not exceed $75,000 per year in total costs. The total project period for an SRF02 application submitted in response to this RFA may not exceed two (2) years. These grants are non-renewable and continuation of projects developed under the SRF02 program will be through the SRF01 grant program.
New Faculty grants (SRF03) may not exceed $125,000 per year in total costs, and grants for up to two years will be considered.

RESEARCH OBJECTIVES
The pathogenesis of scleroderma is complex and not well understood. Immune activation, vascular abnormalities and dysregulation of extracellular matrix components contribute to end-stage obliterative vasculopathy and fibrosis. Host and environmental factors may contribute to disease predisposition and onset. Although these disease components have been known for some time, their roles in disease initiation and progression are unclear. Research efforts in scleroderma have been focused on the analysis of the immune abnormalities with emphasis on the molecular characterization of autoantibody specificity, autoreactive T cells and cytokine production. Another major research focus has been on the analysis of abnormal collagen production and the regulatory molecular pathways that control collagen production by fibroblasts. Recently, however, new clues point to host factors related to immune activation and regulation of vascular cell activity as potentially key early events in the pathogenesis of scleroderma.

The purpose of this announcement is to encourage investigator-initiated (SRF01; SRF03) and exploratory, developmental (SRF02) research to discover and explore new approaches and hypotheses for the pathogenesis of scleroderma. In addition, the initiative also seeks to promote the development and pilot testing of new therapeutic approaches. Potential areas of research include, but are not limited to:

• Studies of immune activation in scleroderma and mechanisms to selectively control aberrant activation.
• Studies on the initiation and propagation of the fibrotic process in scleroderma; in particular, the interaction of the disease process with the immune system.
• The study of molecular and cellular events that contribute to vascular reactivity and vasculopathy in scleroderma.
• Pharmacologic and alternative approaches leading to reduction of GI symptoms and GI tissue injury in scleroderma patients.
• New approaches to reduce progressive scleroderma lung disease.
• New animal models to elucidate scleroderma pathogenesis and test new therapies.
• Analysis of gene expression patterns that may contribute to disease onset or progression of scleroderma.
• Studies on biomarkers and new diagnostic methodologies to monitor progression of scleroderma.
• Translational studies with currently available drugs to treat scleroderma based on new therapeutic or mechanistic hypotheses.

URLs IN SRF GRANT APPLICATIONS
All applications and proposals for SRF funding must be self-contained within specified page limitations. Unless otherwise specified in an SRF 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.

DUPLICATED AND RESUBMITTED GRANT APPLICATIONS
Applications submitted in response to this RFA that are substantially similar to a grant application already submitted to the NIH or other funding source for review are acceptable. However, the existence of duplicated submissions must be noted in the introduction to the application. If more than one source agrees to fund the application, the investigator will need to select one source; SRF will not fund substantially the same grant. An investigator may submit an application with substantial revisions of applications already reviewed and rejected, but such applications must include an introduction addressing the previous review.

ACCOUNTABILITY
Applicants who accept an award from the Scleroderma Research Foundation may be asked to account for how they have spent their grants. Grant recipients will be required to attend the annual SRF Scientific Workshop to present their research.

SCIENTIFIC CONDUCT AND IRB APPROVAL
The Scleroderma Research Foundation does not assume responsibility for the conduct of the investigation or the acts of the investigator, because the investigator’s conduct and actions are under the direction and control of the grantee institution and subject to the institution’s medical and scientific policies. Grantee institutions must safeguard the rights and welfare of individuals who participate as subjects in research activities by reviewing proposed activities through an Institutional Review Board (IRB) as specified  by the National Institutes of Health (NIH) Office for Human Research Protections, DHHS (OHRP).  Furthermore, grantee institutions must adhere to current U.S. Department of Health and Human Services guidelines regarding financial conflict of interest, recombinant DNA, research misconduct, and vertebrate animals.  The Awardee's institution must assure appropriate governance of animal studies as well as human studies.

APPLICATION SUBMISSION PROCEDURES

1. Open and Save Molecular Pathogenesis and New Interventions in Scleroderma Research Grant Application.
2. Complete the application according to the above online guidelines.
3. Copy the completed application onto a CD. You may prefer to create a PDF copy of your application and then save it on the CD.
4. Print and Sign the completed application.
5. Ship by overnight carrier one (1) hardcopy of the signed, completed application, research proposal, relevant appendix material, three letters of recommendation and one (1) copy on CD to:


Victoria Slotfeldt
Scleroderma Research Foundation
220 Montgomery, Suite 1411
San Francisco, CA 94104

For more information, contact Victoria Slotfeldt at:
Tel: 415-834-9444
Fax: 415-834-9177
vslotfeldt at sclerodermaresearch dot org

SUBMISSION DEADLINES

• New grants: November 14, 2008.
• Continuing grants: December 31, 2008.

Note: 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 from either the GCRC Program Director of Principal Investigator should be included with the application.

REVIEW CONSIDERATIONS:
Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by the Scientific Advisory Board of the Scleroderma Research Foundation in accordance with the criteria below.

1. Significance.  Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge on the pathogenesis of scleroderma be advanced? What will the effect be of these studies on the concepts or methods that drive this field?
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 methods? 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?
6. Budget.  The reasonableness of the proposed budget and duration in relation to the proposed research. The personnel category will be reviewed for appropriate staffing based on the requested percent of effort. The direct costs budget will be reviewed for consistency with the proposed method 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 project.

REVIEW OF APPLICATIONS SCHEDULE

• Review: March/April 2009.
• Funding Available: April 30, 2009.

GRANT CRITERIA
Criteria that will be used to make grant decisions include:

• Scientific merit (as determined by the SRF Scientific Advisory Board)
• Availability of funds
• Programmatic priorities