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CIRM MAJOR FACILITIES GRANT APPLICATION #FA1-00615-1

Recommendation: Not recommended for further consideration
Element X Score: —
Element Y Score: —
Element Z Score: N/A
Use & Contribution Score:—

Public Abstract (provided by applicant)

This institution proposes to develop contiguous space to house new faculty researchers to be added to those already participating in the existing stem cell research center. This will expand a strong campus commitment to studies pertaining to stem cell research, translational research and regenerative medicine. The proposed renovations will provide approx. 10,000 assignable square feet (asf) of laboratory, office, vivarium and support space, including barrier animal housing and animal imaging instruments to allow analysis of in vivo models. The space will be renovated in a building adjacent to a new stem cell core facility, which was recently funded by a CIRM Shared Research Laboratories Grant.

The existing stem cell research center includes at least five faculty members who have active research projects in basic stem cell science and human embryonic stem cells (hESC). Two of these have CIRM SEED grants, in addition to the CIRM-funded core facility. Another 5-6 existing researchers plan to incorporate basic stem cell studies and/or hESC studies into their research programs in the coming 5 years. Existing faculty members also have active scientific collaborations on stem cell projects with researchers from several institutions in the region. The campus has already approved additional faculty hires in stem cell science; two formal hiring offers have been made (under active consideration as of the date of this application), and at least two more faculty hires in this area are included in near-term campus plans. A long-range goal is to make regenerative medicine a major research theme of the campus and the associated medical school.

The existing stem cell research center has three active research lines that fit into CIRM Element* X*: 1) high-throughput analysis of functional markers and expressed components of stem cells, both in the pluripotent state and during differentiation to dedicated tissue types; 2) studies of the effects of the environmental niche (associated cell types, environmental conditions, cell communication, etc.) on stem cell pluripotency and differentiation; and 3) analysis of signaling factors and signaling mechanisms that are important in the retention of pluripotency and/or the departure from pluripotency to differentiation.

In addition, both the existing stem cell researchers and those yet to be hired will contribute to CIRM Element Y in the following areas: 1) development of new technologies and assays for markers of pluripotency and differentiation; 2) development of animal models for the role of stem cells in disease processes and the treatment of disease; 3) assessment of compounds or signaling factors as drug discovery candidates; and 4) studies of the role of stem cells in development or treatment of specific human disorders such as muscular dystrophy, Alzheimer’s disease, or birth defects.

Statement of Benefit to California (provided by applicant)

When Californians resoundingly passed Prop 71, they demonstrated the importance of stem cell research to all the citizens of our state. This proposal meets the challenges of working with stem cell science toward treatments for human diseases and disorders. The proposed Stem Cell Center will benefit all Californians by expanding the scientific research program in this institution, as well as improving the ability of the institution to serve as a regional focus for training of scientists and physicians interested in using stem cells for research, and ultimately for treatment. The Stem Cell Center will allow research using non-federally funded hESC lines, and will service a group of highly accomplished investigators at the host and neighboring institutions in the most ethnically and culturally diverse and fastest growing region of California. The investigators are at the top of their respective fields, have a range of hESC expertise and are committed to applying their experience to some of the most critical issues facing the field of regenerative medicine today. The group is highly interdisciplinary and has an established history of productive interactions and collaborations. They have created a new network of extended collaborations, aggressively fostering stem cell research in the area, and have secured substantial extramural funding for their research. The proposed users have existing projects that directly impact our understanding of the basic biology of hESC and will generate new findings that will be essential to the successful development of stem cell-based therapies.

Review Report

Executive Summary

This institution proposes to develop a Center of Excellence for stem cell research in Elements X and Y by renovating space to house five PIs. The additional space will provide approximately 10,000 square feet (sf) of additional laboratory, office, vivarium and support space. An existing vivarium will be expanded and renovated and will include space for animal imaging. There is already an existing fifteen-participating faculty as part of an existing stem cell center and five principal investigators (PIs) actively working on stem cells in research projects. Three of the five PIs have active CIRM grants. The institution has already approved another four new hires over the next 3-5 years in stem cell science, and formal offers have been extended to two candidates. The institution is opening a medical school in 2012 2013 and a major research theme will be regenerative medicine.

The scientific focus of Element X is on three areas: high-throughput analysis of stem cells, studies on the stem cell niche, and analysis of signal transduction mechanisms that are important for retaining pluripotency versus differentiation. Element Y will consist of developing new technologies and assays for markers of pluripotency and differentiation. Also, animal models will be developed to determine the role of stem cells in disease processes and treatment of disease. The focus will be on diabetes, Parkinson’s disease, Alzheimer’s disease and birth defects.

The strength of this application is that the institution will build on an already growing and strong program: existing faculty have active CIRM grants, and the institution was awarded money for a CIRM Shared Research Laboratory. The resources provided by CIRM in this award would help expand the physical space to house additional researchers.

Weaknesses outweighed the strengths for this proposal, however. A major concern is that although individual faculty have excellent and focused research programs, there is little evidence for intra- and inter-institutional collaborations. Furthermore, this institution has already received substantial funds to build one building, and it is not clear what the justification is for this second building given the size of the faculty – these new funds would renovate a neighboring building to house very few additional researchers. Finally, although two of the PIs are in place for Element X, no one is in place yet for Element Y and it is not clear that the hiring plans detailed will be successful. The translational component thus lacks a core group of faculty. This is a weakness and the institution should seek outside help to recruit new members with expertise in drug discovery/translational medicine for this initiative.

Reviewers felt that the institution’s stem cell project was at too preliminary a stage to justify supporting the current application, especially since there is no medical school as yet. Although the institution does have 15 stem cell biologists, some of them outstanding, the program is in its infancy and suffers from a lack of coherence. Reviewers were not of the opinion that this core group constituted a critical mass to ensure a successful stem cell science program. They also questioned the decision to build such a small building, which would only accomodate 4-5 scientists.

Detailed Summary

Element X

Score: —

SCIENTIFIC PROGRAM: The proposed CoE would be created by renovating space to house up to 5 PIs.

Quality of programs within and outside the facility:

There are two PIs listed for the new space that are already participating in the stem cell center. One of the PIs is interested in non-coding RNA in Drosophia and mice and his/her hypothesis is that the noncoding RNA controls the differentiation of hESC. Another is focused on signaling pathways that initiate heterogeneity in hESC. Both of these PIs represent a scientific strength to this proposal, and one of them has received CIRM funding. Three PIs who will not be housed in the new facility are currently active in stem cell science, and two of these are funded by CIRM. One PI’s projects were noted as being well-defined and important. A few more projects are discussed but no biosketches are attached so the reviewers had difficulty assessing their scientific importance. The application states that there are other faculty members who have an interest in using stem cells in their research in the near future within 3-5 years, which seems very much in the future. Their work would add to the critical mass but the interactions were not defined. Overall some of the projects appear interesting and exciting ideas are presented; the investigators are very qualified and there seems to be a focus on high-throughput applications. However, it is unclear that there are enough stem cell investigators at the institution to achieve critical mass in stem cell research.

FORMAL INSTITUTIONAL COLLABORATIONS: No formal collaborations are defined for this proposal. However, there are some active scientific collaborations with scientists at at neighboring institutions. No details are provided so strengths and weaknesses cannot be enumerated. The assumption is that this will provide synergies with the additional new PIs.

CORE SERVICES: A core facility has been funded by CIRM under the shared research laboratories program and will be completed in 2009. This facility will be in a building also containing core facilities for genomics, proteomics, array services, microscopy, imaging, bioinformatics, and flow cytometry. The proposed new facility will be constructed next to the existing stem cell facility, making these cores be available to the new building. The new building will house a vivarium.

PLANS FOR GROWTH: The institution is committed to adding four new faculty for the stem cell center, and the commitment is increased around a planned new medical school for 2012 with a strong interest in regenerative medicine. This is a strength of this proposal. There are also a number of researchers using stem cells that are outside the proposed stem cell center, this will potentially continue to grow as individual departments recruit new faculty supporting more interdisciplinary interactions.

DISCUSSION: Although the institution does have 15 stem cell biologists, some of them outstanding, the program is in its infancy and suffers from a lack of coherence. Reviewers were not of the opinion that this core group constituted a critical mass to ensure a successful stem cell science program.

Element Y

Score: —

SCIENTIFIC PROGRAM: Two to three PIs are expected to be housed in the proposed newly-renovated facility that will be focused on more translational research with stem cells. All of these researchers have yet to be hired although two formal offers have been made. They list proposed research areas that seem reasonable but the qualifications and productivity of the proposed PIs cannot be judged at this time.

Quality of programs within and outside of facility:

Three to four PIs who will not be in the new facility are currently active in stem cell science. Two of these are funded by CIRM. There are others who have an interest in using stem cells in their research in the near future within 3-5 years. This will add to the critical mass but the interactions were not defined.

FORMAL INSTITUTIONAL COLLABORATIONS: Again, no formal collaborations are defined for this proposal however there are some active scientific collaborations with scientists at neighboring institutions. No details are provided so strengths and weaknesses cannot be enumerated. The assumption is that this will provide synergies with the additional new PIs.

CORE SERVICES: A core facility has been funded by CIRM under the shared research laboratories program and will be completed in 2009. This facility will be in a building also containing core facilities for genomics, proteomics, array services, microscopy, imaging, bioinformatics, and flow cytometry. The proposed new facility will be constructed next to the shared research labs.

PLANS FOR GROWTH: Primarily an expansion of space is proposed. The institution is committed to adding four new faculty for the stem cell center and the commitment is increased around a planned new medical school for 2012. One reviewer felt that this is a strength of this proposal, although others felt that the plans for expansion were inadequate. There are also a number of researchers using stem cells that are outside the proposed facility, this will potentially continue to grow as individual departments recruit new faculty supporting more interdisciplinary interactions.

DISCUSSION: This section of the application is even more premature than Element X, and reviewers were surprised that it was proposed. Reviewers commented that the ideas are good, but there are no faculty involved as there is no translational activity in the institution at this time. The institution hopes to recruit two new faculty for translational activity, and the application describes what sort of applicant they are looking for, but no one has been identified yet (one reviewer noted that the institution might need the space in order to recruit the faculty). All existing faculty that are identified in this element are people not working in human embryonic stem cells; although the application states that they hope to do it in the next 3-5 years, reviewers pointed out that this statement was vague and non-committal.

Use & Contribution

Score: —

The requested funds would renovate a building neighboring an existing CIRM Shared Laboratory facility to house up to 5 researchers. Although two of these PIs are already at the institution, no one is in place yet for Element Y and it is not clear that the hiring plans detailed will be successful. The renovations would provide 10,000 sf of office, laboratory, and support space, and a vivarium adjascent to the existing Stem Cell Center. Reviewers commented that there was little thought dedicated to inter- and intra-institutional collaborations or to integration of the projects in this proposal.

Programmatic Discussion

 

A motion was made to drop this application from a two-element CIRM Center of Excellence to a single element CIRM Institute application. Panelists commented that there are many good people with NIH grants listed in Element X, and the institution would like to bring on new faculty. However, reviewers commented that even Element X has a lower score than the programs that were funded in the single-element section. Panelists commented that CIRM has a limited fund for facilities, and there are many applications in the pool that are much better than this one. It is hard to point to a unique feature in this application that would justify saving it, and panelists did not see a key programmatic reason for keeping it. The motion to recommend for consideration as a CIRM Special Program (Single Element) did not pass.

The following Working Group members had a conflict of interest with this application and were therefore recused from participating in review of, discussion of, and voting on the application:

• Penhoet, Ed