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CIRM MAJOR FACILITIES GRANT APPLICATION #FA1-00611-1
Recommendation: Recommended for further consideration as a CIRM Institute
Element X Score: 85
Element Y Score: 90
Element Z Score: 83
Use & Contribution Score: 88
Public Abstract (provided by applicant)
The proposed new CIRM Stem Cell Institute, to be located at a major public university, will be the center of scientific and clinical activity to bring stem cell therapies to patients in the State of California. This institution has a long-standing reputation for being highly collaborative, sharing resources and infrastructure, and for providing outreach and expertise to other educational and medical facilities. Our geographical location and service to diverse communities will ensure that stem cell treatments are provided to patients that desperately need them. The rapid renovation of undeveloped space in a large existing building adjacent to our medical center and clinics will establish a new home to co-locate disease teams that span basic, translational, and clinical strengths. This setting for disease team-based research will forge collaborative networks, promote communication, and accelerate development of clinical trials for the treatment of human diseases. The disease teams include, but are not limited to, investigators working together toward therapies for liver, kidney, heart, and lung diseases; bladder reconstruction; peripheral vascular disease; neurodegenerative disorders (e.g., Parkinson’s, Huntington’s, and Alzheimer’s disease); vision and hearing loss; blood and immune system diseases including HIV/AIDS; skin diseases and burns; and cartilage and bone disorders, affecting patients of all ages (children to aging populations). Stem cell clinical trials in four of these areas are currently pending, and will be performed in a state-of-the-art 6-suite Good Manufacturing Practice (GMP) clean room facility for cell processing, currently ready for construction based on plans that are FDA-approved. This facility will be linked with an established clinical trials infrastructure that will enable researchers to readily move cellular therapies into patients after conducting safety and efficacy studies in a wide range of preclinical models unique to this institution. In this planned facility, researchers will explore the basic biology of stem cells, take these cells through preclinical testing, and perform stem cell clinical trials. This new Institute will aid in meeting the Stem Cell Program objectives of teaching and training students, fellows, and staff; and promoting synergy that will result in vast improvements in health care for patients and communities in California.
Statement of Benefit to California (provided by applicant)
Our institution has a strong track record and aggressive plans for the development and testing of new stem cell therapies for treating a spectrum of human diseases across the lifespan, from young children with disorders that cause kidney damage prior to birth, to aging individuals in our community where health problems, such as those associated with Alzheimer’s disease, hearing loss, and osteoporosis, significantly impair quality of life. Building on the depth and breadth of science and medical assets on our campus, the Stem Cell Program and the proposed new CIRM Stem Cell Institute will provide a home and coordinating location for the many scientists, physicians, students, fellows, and staff working together to develop new treatments for diseases that could be prevented, reversed, or ameliorated by stem cell therapy. Research teams will work together side-by-side to study and treat health problems related to liver, kidney, heart, and lung diseases; neurodegenerative disorders such as Parkinson’s, Huntington’s, and Alzheimer’s disease; vision and hearing loss; infectious diseases such as AIDS; circulatory problems that result in loss of limbs and poor heart function; diseases of cartilage and bone; and skin conditions such as non-healing ulcers and burns. The new facility will serve the state and its citizens by providing unparalleled opportunities to investigators, and will establish a model for the manner in which teams can work together to advance the use of stem cell therapies for human diseases. The proposed Stem Cell Institute will remove barriers preventing the transfer of promising stem cell therapies to patients by connecting investigators with expertise and new ideas with the resources necessary to develop and to evaluate new technologies and therapies. This facility will be devoted to stem cell research, and will provide basic and translational laboratory space as well as accelerate testing of human stem cells in a variety of unique preclinical models. It will also house a large Good Manufacturing Practice (GMP) clean room facility for performing clinical trials. The GMP facility will be available for all California investigators with evidence of promising therapies. The California community will benefit from the results of this collaborative environment because it will facilitate and advance research findings, promote a culture of sharing, and educate and train a new generation of scientists in stem cell research. The facility will be home to 31 investigators and at least as many collaborating scientists as well as regional partners, and aid in meeting the Stem Cell Program and CIRM objectives of accelerating the applications of stem cell biology to clinical use, and forming teams to focus on improving health care for patients and communities in California.
Review Report
Executive Summary
The applicant institution is a top public research institute, and has proposed bringing together several specific disease-focused teams of basic scientists (Element X), preclinical model experts (Element Y) and clinical investigators along with Good Manufacturing Practice (GMP) expertise (Element Z) into a CIRM Stem Cell Institute. The applicant institution is a large university, annually trains the largest number of biological science PhDs in the state and has one of the fastest growing Schools of Medicine. The proposed CIRM facility will be home to 31 investigators and at least as many collaborators.
The application requests support for renovation of existing space to provide an intellectual and physical home for stem cell research on the campus that will occupy the same building and be adjacent to a clinical translational science center. The proposed Institute will focus on multidisciplinary translational approaches in stem cell research from basic to clinical investigation. This setting for disease team-based research will forge collaborative networks, promote communication, and accelerate development of clinical trials for the treatment of diseases. Key areas to be explored as part of the stem cell program are liver, kidney, heart, and lung diseases; peripheral vascular disease; neurodegenerative disorders (e.g., Parkinson’s, Huntington’s, and Alzheimer’s diseases); vision / hearing loss; blood and immune system diseases including HIV/AIDS; skin conditions including non-healing ulcers and burns; and cartilage and bone disorders.
The application presents a clear effort in developing and enhancing programs in human embryonic stem cell (ESC) differentiation, but the current basic program is still nascent with only few publications on human ESC. While the existing effort is not yet strong, the ideas proposed are very innovative and multidisciplinary in nature. The effort is organized according to disease areas, some of which are not being commonly pursued by other stem cell programs. The applicant institution also incorporates interesting technologies such as collaborations with a textile group to create special fibers for biological use. There is also strength in genomics and high-throughput screening (HTS) applications to characterize cells. Another key asset of the applicant institution is the preclinical modeling effort and expertise in a breadth of preclinical models.
The applicant institution has successfully competed for CIRM grants including for the Stem Cell Training Program, SEED and Comprehensive grants, and a grant for a Translational Human Embryonic Stem Cell Shared Research Facility.
A relative weakness of the application is that some of the investigators are not of comparable caliber and current productivity compared to investigators at stem cell programs at some other large institutions. Overall, the investigators do not represent the same depth and quality of these other large institutions. In the area of hESC research, very little published evidence of achievement exists. However, the innovative projects proposed and the clear evidence for interaction and translation are positive points. The organizational operation of the proposed program is also not very well structured with no defined internal and external advisory and steering committees.
For each element (X,Y, and Z), reviewers’ comments are summarized below. In the area of basic research (Element X), the applicant institution has a strong basic science faculty. Disease-oriented programs are supported by technological innovations. This combination allows some highly innovative aspects, including unique technologies for more efficient high-throughput screening, and an innovative collaboration with the Department of Textiles and the development of nano-fibers as cell scaffolding for transplantation. One reviewer noted that this was one of few if not the only institution approaching organ replacement from this perspective. Another strength cited was the history of translational excellence at the applicant institution (including adult and fetal stem cells, and genetically modified treatments). This strength, along with the excellence in preclinical model experience (both murine and clinically relevant models), would allow for rapid translation of basic science discoveries.
The programs, faculty and core support for Element Y, and the institution’s track record in performing preclinical studies, were felt to be the strongest part of the proposal. The directors and investigators in this element were believed to have considerable experience in the translation of basic science findings into preclinical and clinical testing. Again, it was noted that the group has exceptional experience with adult and fetal stem cells, and with genetically-modified treatments, and these should help pave the way for hESC-derived therapies. While this was viewed uniformly as strength, at least one reviewer saw it as potential weakness of the development of hESC-based treatments, from a capacity viewpoint. This reviewer commented that plans for adult and fetal programs are so ambitious that it could detract from the goal of advancing hESC-derived therapies to the clinic. Another strength noted by all reviewers was the applicant institution’s experience with clinically relevant models. Preclinical models, facilities and expertise were highlighted as exceptional strengths of the applicant institution. An innovative immune-deficient murine model was highlighted by all reviewers, along with general institutional breadth in preclinical models. A final strength noted by reviewers was the applicant institution’s track record for assembling multidisciplinary teams. On balance, the proposal for Element Y was viewed by all reviewers to be the strongest part of the application, especially in conjunction with a unique and high quality large animal facility that is important for advancing stem-cell based therapies to the clinic.
Element Z was noted for: the applicant institution’s experience with adult stem cell clinical studies; its access to a large, diverse population from which to draw upon for clinical studies; and its strength in GMP production. Reviewers noted that plans for the GMP facility were already approved by the FDA; therefore, the facility could be rapidly completed upon approval of the application. Reviewers felt this to be a significant milestone that has already been met in building such a facility. The same criticism in this element was one noted throughout the application. No descriptions were provided about how the applicant institution plans to derive clinically useful cell products that are not autologous-derived, and therefore reviewers could not assess the applicant institution’s ability to qualify hESC or fetal-derived cell products for use in human studies. Despite this criticism, the panel enthusiastically supported the application.
Detailed Summary
Element X
Score: 85
SCIENTIFIC PROGRAM: The programs that will be housed in the proposed facility are organized around disease specific teams. In the new facility these will be focused on basic and discovery research focused on four main disease areas: liver disease, kidney disease, bladder reconstruction, and heart disease. Programmatic themes include hESC directed differentiation (e.g. hepatic, kidney and bladder, cardiovascular, pulmonary, neurosensory and neural) and related research (cell-cell communications, genetic modification); the study of microenvironments and biomaterials; and the use of high-throughput and other technologies to evaluate cells, supported by investigators both on site and linked to their collaborating institutions. Reviewers noted that the lead investigators in the disease areas have varying levels of experience with hESCs. Two of the four PIs have experience in hESC, one is entering the field and another PI has supporting expertise in his / her group.
The liver disease program is led by an established hESC investigator and spans basic, translational, and clinical studies. The application details numerous collaborative efforts between this team and other investigators for preclinical evaluation of potential therapies for liver disease. Other aspects of note are novel cell culture tools for screening, robotic technologies for creating arrays, the use of matrices for examining stem cell-surface interactions, and technologies for creating bioengineered livers. This is a very strong program.
The kidney disease program is also led by an established investigator, and focuses on basic and translational research, including the basic biology of various types of stem cells (hESC and adult), combined cell and gene-based therapies using a clinically relevant model. This investigator is also the leader of three major facilities at the applicant institution, all of which are relevant to the proposed stem cell facility and programs. Among the novel aspects of this program is an effort, in collaboration with bioengineers, to design novel scaffolds and matrices for effective transplant applications. The investigator is noted to have a strong program, and including him / her in the CIRM facility will help ensure effective team integration and collaboration in the translation of basic science to clinical investigation.
In the area of bladder reconstruction, the program will evaluate a variety of cell types, including bioengineered tissue and hESC, if the cells can be successfully differentiated. This investigator will benefit by being in close proximity to the liver and kidney teams.
The heart disease teams will focus on addressing a wide variety of cardiac arrhythmias. One reviewer commented that it seems this team has been able to reconstruct a tissue to replace an electronic pacemaker, and called this “an amazing feat”.
Overall, the investigators who will be in the CIRM facility create a very strong basic science program with many potential synergies in addressing similar problems in each of the four disease categories. Each of the PIs has a good individual track record in terms of productivity, and clear evidence for collaboration with fellow colleagues.
The application indicates campus research efforts outside the facility will also be organized around disease specific teams and technology-based support services, with significant opportunities to collaborate with CIRM-based faculty and core activities. Several examples noted in the application included: neurodegeneration; lung disease; stem cell biology and cancer; cell signatures and characterization; and microenvironments, biomaterials, and tissue engineering. Reviewers also noted strong programs in genomics and cellular biology, epigenetics, developmental biology, bioinformatics and biostatistics, based at various locations throughout the campus of the applicant institution. In summary, reviewers felt that investigators outside of the CIRM laboratories have a very strong basic science research program, with many potential synergies in addressing similar problems with the CIRM-based faculty. However, one reviewer noted that there has been only very limited proof of concept for any of these disease areas by faculty at the applicant institution, and PI productivity was judged to be moderate in basic hESC research, based on publications.
Another weakness noted by reviewers is if the applicant institution intends to move forward with hESC-derived therapies, it will be important to have appropriately derived and documented cell lines. This was not described in the application.
FORMAL INSTITUTIONAL COLLABORATIONS: The applicant institution has a strong affiliation and established formal collaborations with a nearby hospital and major research institute. There is a recent collaboration with a second research institute to leverage the collaborator’s expertise in aging research and age-associated diseases. Formal MOUs were included in the application documenting these collaborations.
CORE SERVICES: In the proposed CIRM facility, two major Cores are listed under the Element X heading of the application (additional Cores are included in Element Y and Element Z). Those two cores are FACS and Microscopy. A wide variety of other core support services are available throughout the campus. Of note are genomics, proteomics, metabolomics, and in vivo imaging shared resources. It is clear that the applicant institution has an excellent track record in the management, operation, maintenance and productive use of such cores. The applicant institution has a tech transfer department that focuses on protecting and commercializing intellectual property. The application details significant success for this department in executing license agreements, coordinating invention disclosures, executing MTAs. All of these core services are available to CIRM and outside investigators for defined user fees.
PLANS FOR GROWTH: Within the proposed CIRM facility, the applicant institution has a strategic plan with focus areas in Cancer, Neuroscience, Vascular Disease, and Infectious Disease. A few faculty positions are planned to be recruited; half will be in basic research and will help expand hESC expertise. Additional space will be utilized for educational activities such as conferences and training in formal courses related to stem cell biology and bioethics. The proposed CIRM facility is critical to the new recruitments. Outside the proposed facility, all of the applicant institution schools have plans for expansion. There is a new initiative, the Alzheimer’s disease center with a focus on neural progenitor cells, which was the only specific aspect mentioned in the application.
Element Y
Score: 90
SCIENTIFIC PROGRAM: The proposed CIRM facility will enhance translational efforts by promoting disease teams and linking the basic and clinical themes. It will build on a major strength in preclinical models, including clinically relevant models. In particular, the new immune-deficient mouse facility will allow investigators to use xenotransplantation to evaluate new human stem cell-based therapies as they are developed. Seven of the total 31 faculty planned to be housed in the CIRM facility will be housed in Element Y space; these areas will be divided by disease focus rather than PI-specific research interests. The concept is to use shared space to rapidly test cells and new protocols by transplantation into immunodeficient mice. Promising approaches will then be evaluated in larger animal systems, and further assessed under FDA GLP guidelines in appropriate preclinical models.
The director of the stem cell program at the applicant institution will also serve as director of the GMP facility. This investigator has a very strong focus on hematopoietic and mesenchymal stem cells, and has been involved in some of the very early gene therapy trials. The investigator is one of the world’s leading experts in the use of immunodeficient mouse models, and as such is the perfect person to lead the preclinical research aspects of the proposed CIRM facility. The investigator has extensive ongoing collaborations with other CIRM faculty at the applicant institution.
The remaining Element Y space will be divided into separate disease focus areas: 1) HIV/AIDS and HSC, 2) retinal degeneration, 3) skin disorders and wound healing, and 4) cartilage regeneration and bone repair. The application details several PIs and programs that are already active in each of these areas of preclinical research, many using the immunodeficient mouse or other clinically relevant models. Many of these appear to be very productive investigators.
An important aspect of this element is the translational stem cell research center. It will be located outside the proposed facility, and is a critical multidisciplinary, multi-institutional partnership that unifies basic science, translational, and medical functions for a common goal the advancement of cell-based therapies for the treatment of childhood diseases. The center projects are: endothelial progenitors for HSC, maintenance and cord blood expansion, fetal renal replacement strategies, and imaging of human stem and progenitor cells in large animal models. Another separate institution noted by the reviewers is a shared resource for the evaluation of cell and gene transfer for heart, lung, and blood diseases.
The key overall strength of the Y-component of this application is in the remarkable breadth of animal models, and the enormous capacity for large animal studies. The applicant institution has a strong focus on translational medicine, and this should provide quite a unique opportunity to move studies efficiently from X to Y to Z. Given the strength of the Y-component of the application the question could be raised whether the quality of the basic research pipeline in X is adequate for the overall efforts. The strategic recruitments proposed for X may address this issue.
The only weakness discussed in this element was by one reviewer who would have liked to see discussion of potential approaches for optimizing large animal models for potential hESC-therapy testing.
FORMAL INSTITUTIONAL COLLABORATIONS: In addition to the previous described academic collaborations in Element X, the applicant institution also has a formal relationship with a commercial organization for processing, cryopreservation, and storage of human progenitor cells.
CORE SERVICES: The main core facilities relevant to the Y-component of the proposal include a Vector Core and a vivarium. A number of preclinical models will be available to the investigators that are particularly useful in the context of cell transplantation. There is also an imaging center that provides state of the art in vivo imaging capacity for preclinical studies.
The applicant institution has a wide variety of shared resource cores that would be available to CIRM faculty, located outside the facility. Of particular note is the world-class preclinical model facility, which is fully loaded with cell culture, flow cytometry, RT-PCR, histology, controlled freezing, and experienced personnel. Other noteworthy cores include: clinical labs, a mutant mouse resource center, a department of Animal Science, in vivo imaging resources, and a clinical translation center. The clinical translation center includes numerous support services including: technology transfer support, research education, training and career development, regulatory knowledge, and support for IND/IDE applications.
PLANS FOR GROWTH: Plans for growth include the recruitment of a few new faculty members with their hires contingent upon the outcome of basic and translational studies and expansion of a core resource. Outside the facility, growth is expected within areas dedicated to translational extensions of stem cell efforts throughout the state of California.
Element Z
Score: 83
SCIENTIFIC PROGRAM: The applicant institution has a huge medical outlet with nearly 1 million annual clinic visits and plays an important role in engaging a diverse part of the population into clinical research. Many centers at the applicant institution have been at the forefront of engaging diverse populations in clinical research. More than 1,000 health-related research studies are carried out annually involving basic science, translational, and clinical trials research.
The Z component of the proposed facility centers around efforts to move forward with clinical trials in the stem cell arena and to develop new stem cell based trials. These trials will be enabled by a new 6-suite, state-of-the-art GMP facility that will be housed in the new building. The facility has been approved by the FDA in a type “C” meeting and is ready to be submitted for bid.
There is a track record in clinical trials in the stem cell field at the applicant institution with currently four adult stem cell therapy trials pending (3 IND applications submitted, 1 pending submission). The infrastructure established in these trials using adult stem cells should be useful for the future translation of hESC derived cell populations.
The applicant proposes to maintain the GMP facility using a business model based at least in part on recharge rates. The facility is anticipated to become a shared resource available for California investigators. There is clear GMP expertise available to run the facility. However, the program is extremely ambitious in scope with a huge number of trials proposed that are not all that innovative and may somewhat detract from the long-term goal of translating these efforts to hESC-based products. The faculty will be focused on the same set of disease categories listed in the Elements X and Y: liver repair, peripheral vascular disease, cardiovascular disease, blood cell disorders, HIV/AIDS, retinal degeneration, epithelial repair, lung disease, cartilage regeneration, and neurodegenerative diseases. The application details numerous examples of preclinical and clinical studies in each of these areas, involving various types of stem cell populations.
As noted previously, descriptions of methods and procedures to derive clinically useful cell populations when they are not autologous-derived are missing from the application. For example, it is not clear that a plan is in place to qualify hESC cells lines or fetal hepatocytes for injection into patients.
In summary, there is clear expertise in Z-related activities with clinical trial expertise and excellent expertise in GMP facilities and production. However, the proposed program seems very ambitious and rather diffuse in scope.
FORMAL INSTITUTIONAL COLLABORATIONS: The applicant institution medical center is a large tertiary-care referral center, with more than 100 on-site specialty clinics and a large primary care network. The application describes relationships with the Community Hospital Network, a network of two regional cancer centers and more than ten rural and community hospitals in a region of California. The collaboration with the Community Hospital Network could be potentially valuable for recruiting diverse patient populations for future clinical trials with a strong infrastructure for trials available already. There is clear evidence that the applicant institution should be able to draw in sufficient patient numbers to fulfill the accrual needs of the proposed clinical trials. No other collaborations are discussed in the context of the Z-component of the application.
CORE SERVICES: Inside the planned facility, the only proposed Core under Element Z is a large planned GMP facility. The facility has passed FDA validation and the plans are ready to be sent out to bid. It is a multi-use facility with multiple separate manufacturing suites, completely segregated from each another. The descriptions of operations, validation, and other critical processes are fine. The director of the stem cell program, the GMP Laboratory Scientific Director, the GMP Laboratory Medical Director, and the GMP Laboratory QC Supervisor were all confirmed by reviewers to have excellent experience. One key member has participated in 17 clinical gene therapy trials, but has less expertise in cell based trials. One investigator who will also interact with the GMP facility has considerable expertise in the design of clinical grade vectors. Two of the key directors will work with investigators in developing protocols for making experimental procedures utilized in early translational research (Y) compatible with GLP/GCTP/GMP procedures required for clinical studies (Z). They will also provide general training in GLP/GCTP/GMP to students and investigators at the institution. This is a clear strength and should reduce the threshold for some of the investigators to move projects towards clinical trials.
There were some potential concerns with the facility design. Capacity may still be limiting if the usual rule of one patient per incubator is followed, especially because some types of culturing may require extensive periods of time. It was not clear how specimens come into the facility, nor how in-process and final QC samples exit the facility for external testing. Similarly, unidirectional flow restrictions could cause problems.
Outside the planned facility the applicant institution has an extensive set of shared resources to support Element Z. There are the NIH-sponsored clinical translational center, the NCI-designated Cancer Center with a specimen repository, the pharmacokinetics shared resource, and a telehealth resource program.
PLANS FOR GROWTH: The application described no well formulated growth plans for component Z within the facility. The applicant stresses interaction with the main focus areas of the institution. Growth in the Stem Cell Program should happen in coordination with these areas and the remaining space in the building would be reserved for such joint appointments. Outside the proposed facility, expansion is planned in the area of cardiovascular medicine / stem cell research with recruitment of an internationally known interventional cardiologist. The recruit is interested in the stem cell efforts, and this investigator has run multiple clinical trials in cardiology. Recruiting in this investigator’s program may be synergistic with the stem cell efforts. Another area of expansion is in a technology that has the potential to contribute to stem cell therapies by providing non-intrusive methods to characterize bioengineered tissue.
DISCUSSION: Reviewers agreed that the medical center has a long history of performing clinical trials, and has the greatest access to diverse genetic populations. These characteristics make it one of the most interesting proposals. The applicant institution has shown it can translate basic science findings to the clinic, since a number of trials are on-going, all with adult cells. One reviewer commented that it would be good to see a number of projects in the pipeline that are in hESCs. Based on the track record, this reviewer felt that if the institution hires the right people, it has the ability to make the transition to hESCs.
Use & Contribution
Score: 88
The applicant has well developed plans that should allow immediate renovation and establishment of the proposed state-of-the art research space. The building is set up for collaboration though there seems to be clear separation between X and Y elements.
The new facility will be the home for 31 investigators, 14 completely housed, 17 partially housed, in the renovated space. The term partially housed means these investigators will have their primary laboratory space at other campus locations but through their collaborations will have bench space and workrooms to conduct their studies in the facility. In addition the space will be used for almost as many collaborators that should provide opportunities for multidisciplinary interactions. The new center should serve as a hub for stem cell related activities that are currently dispersed all over the applicant institution campus.
The existing building includes undeveloped space dedicated for future growth of the Stem Cell Program and for additional recruitments. The building also contains the clinical translation center which is highly synergistic in its goals with the stem cell program. One of the goals of these plans is to co-locate investigators according to disease teams but also to relieve space constraints that curtail current growth and productivity. The availability of additional space will be critical to keep up with proposed growth in preclinical testing and to provide access to GMP expertise not readily available in the context of stem cell research at the applicant institution.
The ratio of X:Y:Z space in the proposed facility is 2:3.5:1. There are clearly good reasons to have X-groups interact. With regard to multidisciplinary approaches it would seem wise to also include better interaction between X and Y spaces, which are currently separated in the proposal. In reality most leading stem cell labs will have to be quite strong in both X and Y components. Furthermore, disease-related focus is proposed to transmit discoveries quickly from X to Y to Z that could be enhanced by close co-location. Similarly the additional area of growth may be adequate in total space but it is unclear how they would fit into this X, Y, Z model or into the disease-related organization of the space.
The applicant institution commits start up funds to pay for operating costs of the cores before these cores can become self-sufficient. There is no clear organizational structure for leadership such as steering committees or external advisory boards.
DISCUSSION: Two reviewers recognized that the concept is for shared space, and felt it was a strong concept to promote collaboration and to increase capacity. Members would come in temporarily to do pre-clinical work, and then would move out.
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:
- Feit, Marcy
- Sheehy, Jeff