Comprehensive Grant

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   The goal of the California Institute for Regenerative Medicine (CIRM) is to develop stem cell and related research for the diagnosis, prevention and treatment of disease and injury. Toward that end, CIRM plans to fund a broad and varied program of stem cell research and training, and is currently developing a scientific strategic plan to guide this program. An unexpected development, however, has made funds immediately available that can be used to fund stem cell research before the strategic plan is completed. These funds will be focused on the greatest immediate need, which is research on human embryonic stem cells (hESCs). At a later time, CIRM will offer opportunities for funding across a broader range of projects. 

The first CIRM research grant initiative, Innovation in Human Embryonic Stem Cell Research, is intended to “jump-start” human embryonic stem cell research in California. It will be carried through three Requests for Applications (RFAs), two for individual investigator projects and one for institutional shared laboratory space: 

RFA 06-01: CIRM SEED Grants 

RFA 06-02: CIRM Comprehensive Grants

RFA 06-03: CIRM Shared Research Laboratory Grants and Stem Cell Techniques Course 

The CIRM Comprehensive Research Grant RFA is the second of these three. 


The objective of this solicitation of the Comprehensive Research Grants Program is to support mature, ongoing studies on hESCs by scientists with a record of accomplishment in this field. This is also an opportunity for investigators with well-developed expertise in hESC research or in a closely-related stem cell field to expand their programs or take promising new directions in hESCs research based on current research. In their application, the Principal Investigator (PI) is expected therefore to provide strong preliminary data to demonstrate feasibility and the promise of the proposed research. PIs may be either senior or junior faculty and must be full-time employees of the grantee organization. 

This RFA is open to all academic and non-profit research institutions in California. Future solicitations may be available to for-profit institutions when the CIRM Intellectual Property Policy for for-profit organizations is in place. CIRM also wishes to attract new investigators – young investigators as well as established scientists in other fields – to direct their focus to hESC research. They are encouraged to apply for SEED (Scientific Excellence through Exploration and Development) grants (RFA 06-01), designed to support studies that may yield preliminary data and/or proof of principle that could then be extended to full scale investigations. Unlike Comprehensive Research Grant applications, SEED Grant applications are not required nor expected to have preliminary data. Investigators may apply for either a SEED grant or a Comprehensive Research grant as a PI, but not both. CIRM will accept only one application per Principal Investigator (PI) for one or the other RFA. 


This solicitation is limited to proposals that work directly on hESCs and that can utilize existing space and major equipment at the applicant institution. Funding will be provided for Project costs and other related costs as described in the CIRM Grants Administration Policy. Project costs of up to $400,000 per year for up to 4 years may be requested. The allowable Indirect Costs for this RFA are limited to 25% as described in the CIRM Grants Administration Policy (GAP). 

This solicitation is not targeted to any specific aspect of hESC research or to a particular disease. Topics for investigation should be chosen solely for their potential to add substantially to the body of knowledge on hESCs or to develop a useful research tool or to develop therapy. Future solicitations may be limited to research on topics to be identified through the Institute’s scientific strategic planning process and published as its highest priorities for funding. 

The following are examples of hESC research that are expected to be encompassed within this RFA; applications for other innovative projects will also be considered and are strongly encouraged. 

  • Development of new technology and conditions to optimize the derivation, self-renewal, maintenance, stability, cryopreservation of hESCs.

  • Derivation of disease-specific hESC lines

  • Characterization and comparison of different hESC lines.

  • Understanding the regulation of self-renewal and fate decisions

  • Targeting lineage-specific differentiation of hESCs

  • Assessing the fates of hESCs and their derivatives in animal models of disease

  • Assessing the tumorigenicity of hESCs and their derivatives.

  • Reprogramming of adult human somatic cell nuclei or other new techniques to generate hESCs.  


CIRM intends to commit up to $80 million over a four year period for this RFA. The Institute anticipates that approximately 25 Comprehensive Research Grants will be awarded for no more than a period of four years each. CIRM reserves the right to discontinue or change funding levels from year to year if significant scientific progress is not demonstrated.


All allowable costs for research grants are detailed in the CIRM Grants Administration Policy. 

  1. Salaries for key personnel providing services to the grant. This may include the Principal Investigator, research associate, and/or technical support salaries, based on percent of full time effort commensurate with the established salary structure of the applicant institution. Because CIRM considers pre-doctoral, post-doctoral and clinical fellows as trainees and not as employees, institutions may request stipend, health insurance and allowable tuition and fees as costs for trainees. Administrative support salaries are expected to be covered by the Indirect Costs for the grant.  

  1. Equipment and Supplies Major equipment necessary to conduct the research proposed must already be available at the applicant institution (see definition of equipment in the CIRM GAP). Minor equipment purchases (< $5,000 per item) may be included in the budget. Supplies, including specialized reagents and animal costs may also be purchased with grant funds.  

  1. Travel Recipients (PIs) of CIRM Comprehensive Research Grants are expected to attend an annual CIRM-organized meeting in California and should include in the budget costs for travel to this meeting. Travel costs associated with collaborations necessary to the grant are allowable. Details of allowable travel costs can be found in the CIRM GAP.  


Letter of Intent 

All institutions and investigators planning to apply for a CIRM Comprehensive Research Grant must notify CIRM with a letter of intent (LOI) by September 15, 2006. The letter should describe concisely the overall goals of the proposed research and technical approaches used to achieve these goals. Include a list of proposed out-of- state collaborators; if collaboration with other Californian institutions is planned, this information should also be included. If collaboration with other institutions is planned, this should also be included. In order to facilitate planning for the review of the application, please identify the types of expertise needed to evaluate the proposal. Letters of intent are non-binding, but applications will not be accepted if such a letter has not been provided by the deadline. Letters of intent can be sent as an email attachment to 

Full Application Instructions 

All applications for Comprehensive Research Grants must be received by November 13, 2006. Only applicants who have sent in an LOI will be allowed to submit an application. Applicants must use the CIRM Comprehensive Research Grant Application Form which will be available on the CIRM website by September 15, 2006. 

The application for Comprehensive Research Grants includes: 

  • Abstract (up to 3000 characters): State the goals of the proposal; summarize the overall plans of the research proposed and how it will meet the stated objectives of the proposal. Describe the rationale for these studies and techniques you will use to pursue these goals. Explain the likelihood of this proposal being funded by the federal government.  

  • Public Abstract (up to 3000 characters): Briefly describe in lay language the proposed research and how it will, directly or indirectly contribute to the development of diagnostic tools or therapies. This Public Abstract will become public information; therefore, do not include proprietary or confidential information or information that could identify the applicant (PI and home institution).  

  • Statement of Benefit to California (up to 3000 characters): Describe in a few sentences how the proposed research will benefit the state of California and its citizens. This Statement of Benefit will become public information; therefore, do not include proprietary or confidential information or information that could identify the applicant (PI and home institution).  

  • Specific Aims (up to 1 page): Explain the broad, long-term objectives and the goal of the specific research proposed, e.g., to test a stated hypothesis, create a novel design, solve a specific problem, challenge an existing paradigm or clinical practice, address a critical barrier to progress in the field, or develop new technology. Identify and enumerate each specific aim of the proposal, in a concise and step-wise fashion, and how that will lead to the broad goal of this research. Explain the likelihood of this proposal being funded by the federal government.  

  • Rationale and Significance (1-2 pages): Summarize the context of and background leading to the present application and the specific rationale for the exploratory work proposed. Evaluate existing knowledge and specifically identify the gaps that the project is intended to fill. State how the proposed research meets CIRM’s goals of funding innovative, perhaps scientifically risky research. If the aims of the application are achieved, state how this information will lead to further research that will add substantially to the body of knowledge on hESCs or to the development of diagnostics and/or therapies based on stem cell research.  

  • Research Design and Methods (up to 5 pages): Describe concisely, but in sufficient detail to permit evaluation of the merit of the research, the experimental design, methods and techniques to be employed to achieve the goals specified in the proposal. Identify the new or risky aspects of the research, the anticipated pitfalls, and plans to overcome or circumvent difficulties that may arise. Describe the methods of analysis of results, including criteria for success of the preliminary studies.

  • Preliminary Results and Feasibility (up to 4 pages): Provide preliminary data to support the concepts, hypotheses and/or approaches proposed in the application. Provide any information that will help to establish the experience and competence of the investigator to pursue the proposed project. Does the investigator have access to appropriate technology to perform the research?  

  • Collaboration (up to 1 page): If collaboration is integral to the success of the project, describe exactly how this will be achieved.  

  • Timeline (1/2 page): Provide a realistic timetable for completing each proposed specific aim of the project; where appropriate provide specific milestones for evaluating the achievement of each specific aim.  

  • References (up to 3 pages): List all references used in the body of the proposal.

  • Laboratory/Clinical Facilities including major equipment (up to 1 page): Provide a short description of the facilities and environment in which the work will be done, and the major equipment and resources available for conducting the proposed research. Discuss ways in which the proposed studies will benefit from unique features of the scientific environment or employ useful collaborative arrangements where applicable.  

  • Key Personnel: List the scientific participants and their roles in the proposed research, regardless of whether they will receive salary support from the grant. These may include the Principal Investigator, co-investigators, research associates, technicians and trainees (students and fellows). For each key scientific personnel listed, provide a 2 page biographical sketch that highlights prior stem cell (especially hESC) research experience and/or special skills related to the proposed research. Include relevant publications.  

  • Budget: Provide all budget information requested in the budget section of in the application form.


CIRM Comprehensive Grant applications will be reviewed by the Scientific and Medical Research Funding Working Group (SMRFWG) of CIRM. The SMRFWG consists of fifteen basic and clinical scientists from institutions outside California, seven patient advocates who are members of the Independent Citizen’s Oversight Committee (ICOC), and the Chair of the ICOC. The membership of the SMRFWG can be viewed here. The ICOC was established by the California Research and Cures Act (Proposition 71) to oversee CIRM and makes all final funding decisions. The composition of the ICOC van be viewed here.

Fifteen scientists on the SMRFWG will review the applications and rate them according to scientific and technical merit. The following are among the qualities to be considered for evaluation of research grant applications. For Comprehensive Research Grants,particular emphasis will be placed on impact and significance and quality of the research plan. 

  • Impact and Significance Does the research address an important problem? Will the proposed research significantly move the field forward, either scientifically or medically?  

  • Quality of the Research Plan Is the research carefully planned to give a meaningful result? Are the possible difficulties acknowledged, with alternative plans should the proposed strategy fail? What is the timetable for achieving such significant results?  

  • Innovation Is the approach original? Does it bring novel ideas, technologies or strategies to bear on an important problem? Does it break new ground?  

  • Feasibility Are the preliminary data compelling and support the concepts, hypotheses and approaches proposed in the application? Can the aims of the research by reasonably achieved? Does the investigator have access to appropriate technology to perform the research?  

  • Investigators Do the investigators have the training and experience to conduct the proposed project?  

  • Collaboration Does the proposal support collaborative efforts, and if so, to what extent do the collaborations enhance the quality and potential of the research proposed?  

  • Responsiveness to the RFA How is the proposal responsive to the criteria and objectives stated in the RFA?  

  • Eligibility for Federal funding Is the research ineligible or unlikely to receive Federal funding? If not, is the research sufficiently compelling in that it presents “a vital research opportunity” that will materially aid the objectives of CIRM?  

Recommendations for funding will then be made by the full SMRFWG to the ICOC. In making these recommendations, the SMRFWG will review the entire portfolio of applications, taking into consideration the following criteria: 

  • Scientific and technical merit.  

  • Appropriate balance between innovation and feasibility.  

  • Where relevant, the appropriate balance between fundamental research, therapy development and clinical application.  

  • Where relevant, the appropriate balance and range of diseases addressed.  

  • Other considerations from the perspective of patient advocates.


All Comprehensive Research Grant applications must be submitted to CIRM by November 13, 2006. The application form for CIRM Comprehensive Research Grants will be available on the CIRM website by September 15, 2006. Send a PDF file of the full application to Comprehensive@cirm In addition to submitting the application electronically, send a signed original of the completed application to CIRM. The hardcopy must be signed by both the PI and the institution’s authorized organizational official. Mail the signed hardcopy to: 

Comprehensive Grant Application 

California Institute for Regenerative Medicine

210 King Street 

San Francisco, CA 94107


Receipt of letters of intent: September 15, 2006

Receipt of full application: November 13, 2006

Review of applications: January, 2007

Review by ICOC: March-April, 2007

Announcement of awards: March-April, 2007

Earliest funding of awards: April-May, 2007 

Contact Information 

For review information:

Gilberto Sambrano, Ph.D.

Scientific Review Officer 

California Institute for Regenerative Medicine

210 King Street

San Francisco, CA 94107


Phone: (415) 396-9103 

FAX: (415) 396-9141 

For programmatic information:

Patricia Olson, Ph.D.

Scientific Program Officer 

California Institute for Regenerative Medicine

210 King Street 

San Francisco, CA 94107


Phone: (415) 396-910

FAX: (415) 396-9141

For other information:

Arlene Y. Chiu, Ph.D.

Director of Scientific Activities 

California Institute for Regenerative Medicine

210 King Street

San Francisco, CA 94107


Phone: (415) 396-9104

FAX: (415) 396-9141  


CIRM Grants Administration Policy: 

CIRM’s governing board, the ICOC adopted an Interim Grants Administration Policy (GAP) for Academic and Non-profit Institutions that serves as the standard terms and conditions of grant awards issued by the Institute. All research conducted under this award will be expected to comply with the stated policy, which can be found on the CIRM website. Funding from year to year will depend on scientific progress achieved. 

Human Stem Cell Research Regulations: 

CIRM has adopted medical and ethical standards for human stem cell research. All research conducted under this award will be expected to comply with these standards which can be viewed at on our regulations page. While these regulations prohibit donors of gametes, embryos, somatic cells or human tissue from receiving valuable consideration for their donation, they do allow for reimbursement for permissible expenses as determined by an IRB. “Permissible Expenses” means necessary and reasonable costs directly incurred as a result of donation participation in research activities and may include costs such as those associated with travel, housing, child care, medical care, health insurance and actual lost wages. For research activities proposing to obtain gametes, embryos, somatic cell or human tissue from human subjects, CIRM requires the applicant to submit, at the time of application, their reimbursement policy describing how they intend to calculate permissible expenses.

Intellectual Property Policy for Non-profit Organizations: 

CIRM has adopted policies that govern the intellectual property created under grant awards issued by CIRM to non-profit organizations. Research conducted under this award will be expected to comply with the terms and conditions stated in this policy.


ICOC Approval:
March 16, 2007
Total Awards:
Award Value:


Institution Investigator Grant Title Award Value
University of California, Davis Dr. Mark Zern An in vitro and in vivo comparison among three different human hepatic stem cell populations. $2,251,223
Stanford University Dr. Irving L Weissman MD Prospective isolation of hESC-derived hematopoietic and cardiomyocyte stem cells $2,471,386
University of California, San Francisco Dr. Andrew D. Leavitt MD Understanding hESC-based Hematopoiesis for Therapeutic Benefit $2,460,822
University of California, Irvine Dr Hans S Keirstead hESC-Derived Motor Neurons For the Treatment of Cervical Spinal Cord Injury $2,158,445
University of California, Los Angeles Dr. Jerome A. Zack Ph.D. Human Embryonic Stem Cell Therapeutic Strategies to Target HIV Disease $2,401,903
University of California, San Diego Dr. Yang Xu Mechanisms to maintain the self-renewal and genetic stability of human embryonic stem cells $2,467,200
University of California, Davis Dr. Alice F Tarantal Preclinical Model for Labeling, Transplant, and In Vivo Imaging of Differentiated Human Embryonic Stem Cells $2,166,757
Sanford Burnham Prebys Medical Discovery Institute Dr. Stuart A Lipton MEF2C-Directed Neurogenesis From Human Embryonic Stem Cells $2,832,000
Stanford University Dr. Stefan Heller Generation of inner ear sensory cells from human ES cells toward a cure for deafness $2,330,371
University of California, Irvine Dr. Peter John Donovan Improved hES Cell Growth and Differentiation $2,381,713
Children’s Hospital of Los Angeles Dr. Gay M. Crooks Regulated Expansion of Lympho-hematopoietic Stem and Progenitor Cells from Human Embryonic Stem Cells (hESC) $575,994
University of California, Los Angeles Dr. Gay Miriam Crooks Regulated Expansion of Lympho-hematopoietic Stem and Progenitor Cells from Human Embryonic Stem Cells (hESC) $1,653,416
University of California, San Francisco Dr. Samuel Pleasure Human stem cell derived oligodendrocytes for treatment of stroke and MS $2,459,235
University of California, San Francisco Dr. Harold S Bernstein Dr. Modeling Myocardial Therapy with Human Embryonic Stem Cells $2,134,694
Stanford University Dr. Roel Nusse Guiding the developmental program of human embryonic stem cells by isolated Wnt factors $1,710,462
University of California, Los Angeles Dr. Guoping Fan Dr. Epigenetic gene regulation during the differentiation of human embryonic stem cells: Impact on neural repair $2,412,995
University of California, San Diego Prof. Martin Marsala Spinal ischemic paraplegia: modulation by human embryonic stem cell implant. $2,356,090
Gladstone Institutes, J. David Dr. Deepak Srivastava microRNA Regulation of Cardiomyocyte Differentiation from Human Embryonic Stem Cells $2,994,719
Salk Institute for Biological Studies Dr. Fred H Gage Molecular and Cellular Transitions from ES Cells to Mature Functioning Human Neurons $2,749,293
Stanford University Dr. Renee Reijo Pera PhD Human oocyte development for genetic, pharmacological and reprogramming applications $2,298,411
University of California, San Francisco Dr. Susan J Fisher PhD Constructing a fate map of the human embryo $2,430,487
University of California, Irvine Dr. Douglas C. Wallace The Dangers of Mitochondrial DNA Heteroplasmy in Stem Cells Created by Therapeutic Cloning $1,790,133
University of California, San Francisco Dr. Arnold Kriegstein MD, PhD Derivation of Inhibitory Nerve Cells from Human Embryonic Stem Cells $2,410,874
Stanford University Dr. Christopher K. Zarins Engineering a Cardiovascular Tissue Graft from Human Embryonic Stem Cells $2,454,490
Stanford University Dr. Theo D. Palmer PhD Immunology of neural stem cell fate and function $2,396,000
Sanford Burnham Prebys Medical Discovery Institute Dr. Mark Mercola Chemical Genetic Approach to Production of hESC-derived Cardiomyocytes $2,832,000
University of California, San Francisco Dr. Randall James Lee Embryonic Stem Cell-Derived Therapies Targeting Cardiac Ischemic Disease $2,424,353
University of California, San Diego Dr. Lawrence S. B. Goldstein Using Human Embryonic Stem Cells to Understand and to Develop New Therapies for Alzheimer’s Disease $1,859,414
Stanford University Dr. Julie Baker Functional Genomic Analysis of Chemically Defined Human Embryonic Stem Cells $2,518,303