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Shared Facilities for Stem Cell Research II - 2009

RFA # 0812260816


PI Institution Budget
High-Throughput Screening and Chemistry Shared Facility Christopher Henderson Columbia University Medical Center $5,874,675
Flow Cytometry Core Laboratory to Support Stem Cell Research Andrew Yen Cornell University $1,102,829
Developing an Integrated Platform for siRNA and shRNA-Based Genome-Scale Screens in Eukaryotic Stem Cells Ramanuj DasGupta New York University School of Medicine $5,436,929
An Upstate New York Shared Facility for Basic Stem Cell Research Glenn Monastersky Rensselaer Polytechnic Institute $2,450,561
Shared Facilities for the Stony Brook Stem Cell Center Wadie Bahou SUNY - Stony Brook University $5,503,554
Western New York Stem Cell Culture and Analysis Center Richard Gronostajski SUNY – University at Buffalo $3,564,599
Upstate Stem Cell cGMP Facility Stephen Dewhurst University of Rochester $3,331,362

For more information on NYSTEM-supported facilities, visit our Shared Facilities page.

High-Throughput Screening and Chemistry Shared Facility

Christopher Henderson, PhD
Columbia University Medical Center

Stem cells and different cell types made from them can be used in multiple ways to help us understand and treat human diseases. While some approaches focus on the replacement of missing cells in human patients, stem cells can be used to model diseases in the culture dish, thereby creating an exciting new tool for drug discovery. Using stem cell derivatives from mice or human patients, one can recreate in culture the abnormal process (e.g. death, degeneration or proliferation) that leads to disease in humans. Then, one by one, large chemical collections containing more than 100,000 compounds can be tested for their ability to correct the defect. This is the technique of “high-throughput screening” (HTS).

"Hit" compounds that show activity in the assays need to be further optimized by chemical modification. To provide insights into the molecular mechanism of the disease process, they can be labeled and used for target identification. Alternatively, they can be modified by medicinal chemistry to make them more drug-like, allowing them to reach affected tissues and exert potent effects without causing toxicity.

Summary of Goals and Objectives:
a) Bring high-throughput screening, target identification and medicinal chemistry within reach of stem cell biologists in New York State;
b) Establish a NYSTEM High-Throughput Screening and Chemistry Shared Facility (HTSCSF) to provide access to collections of chemical compounds and gene libraries, as well as all necessary specialized robotic equipment and relevant screening and chemical expertise;
c) Support pilot projects focused on therapeutic development.

This will be the first statewide facility to allow drug screening on stem cell models for a wide range of currently incurable diseases.

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Flow Cytometry Core Laboratory to Support Stem Cell Research

Andrew Yen, PhD
Cornell University

This is an application for support to operate and update a core laboratory resource for fluorescence activated cell sorting and flow cytometry at Cornell University, Ithaca, NY, in order to support stem cell studies.  There is a robust growing group of faculty doing stem cell research that uses the current flow cytometry core laboratory to pursue their studies. A critical common component of such studies is the need to isolate stem cells based on molecular markers and other phenotypic characteristics. It is also necessary to characterize these cells and their derivatives resulting from genetic manipulation, treatment with agents such as growth factors and culture conditions. Flow cytometry is an almost unique tool to achieve these experimental objectives that are critical to much stem cell research as it is able to characterize and identify single cells. This is critical because stem cells are rare in cell populations and their study requires their isolation and characterization. The user group is expanding as are their needs. The current facility would thus be better able to support stem cell research with lower costs to investigators and shorter scheduling lag time. Accordingly this application seeks support for operations to keep user costs low and facilitate research as well as expanded instrument capabilities to accommodate a broader spectrum of experimental procedures. The support sought would thus be for an already operational core laboratory that has technical staffing and direction, strong infrastructure, and administrative management in place. It is thus a proven entity that now needs support to serve better the needs of stem cell researchers at Cornell.

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Developing an Integrated Platform for siRNA and shRNA-Based Genome-Scale Screens in Eukaryotic Stem Cells

Ramanuj DasGupta, PhD
New York University School of Medicine

The primary objective of this proposal is to establish a collaborative, multi-institutional, state-of-the-art, RNA-interference (RNAi)-based high-throughput screening platform. This shared resource will be used for the systematic and comprehensive query of gene function using genome-scale short interfering RNA (siRNA) and/or short hairpin RNA (shRNA) screens in the regulation of self-renewal versus differentiation in a variety of adult and embryonic stem cells (SCs) and induced pluripotent stem cells (iPSCs). A key feature of this proposal is to integrate the complementary expertise, informatics, and technologies available through the RNAi-screening facility at NYU School of Medicine (for siRNA-based high-throughput screening platforms in cultured cells) and the proposed shRNA Core and High-Content Screening Shared Resource Facility (SRF) at Mount Sinai School of Medicine (for lentivirus-based shRNA screens in specific (stem) cell types). The creation of this unique resource, in addition to the availability of human stem cell lines from the hESC-SRF at Mount Sinai will provide unprecedented access to state-of-the-art screening capabilities for stem cell researchers to probe biological pathways using RNAi technologies.

A key feature of this proposal is the commitment to make this integrated platform for siRNA and shRNA-based genome-scale screens fully accessible to the entire scientific community of New York State, which will promote multi-institutional collaborations. Importantly, a major mandate of the integrated screening resource is to encourage sharing of screening data generated at the facility. The creation of a public screen-database will generate awareness of post-genomic screening technologies and encourage academic researchers in New York State to utilize this unique and unprecedented resource. This open access policy is essential to realize the true potential of the functional genomic approaches employed to better understand the biology and regulation of stem cells.

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An Upstate New York Shared Facility for Basic Stem Cell Research

Glenn Monastersky, PhD
Rensselaer Polytechnic Institute

We propose to create a dedicated, shared stem cell research facility within an existing collection of complementary research core facilities in the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute. This facility will be available to all stem cell researchers, with priority use given to NYSTEM-funded New York State-based investigators, and will support fundamental stem cell biology research. The facility staff will provide professional research guidance and training to researchers and will maintain the basic stem cell culture equipment and several sophisticated instruments that will support the culture, study and imaging of differentiating stem cells. A diverse advisory committee will oversee facility policies and operations and provide guidance in stem cell science, ethics and law. The proposed facility will serve the mission of the Empire State Stem Cell Board by providing a valuable, dedicated research resource that will enhance stem cell science in New York State, especially upstate. Research within the stem cell facility will be enhanced by the direct collaboration of several neighboring Rensselaer research core facilities, and their staff members, including advanced microscopy, bioimaging, cell biology, biochemistry, nanotechnology and animal research. These dynamic research cores already serve as a resource for Albany-area academic partners, including SUNY, Ordway, Wadsworth and Albany Medical College. The management and operation of the facility will be supported by the experienced scientific and administrative teams that manage seven existing research cores in the building. The initial user base for the facility will be comprised of more than a dozen investigators, from different institutions, and will grow as the Rensselaer and Albany-area stem cell community grows and matures. The ultimate goal of this effort will be to operate and maintain a reliable, high-quality shared facility that this growing user base will rely on, and use successfully, during and beyond the contract award period.

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Shared Facilities for the Stony Brook Stem Cell Center

Wadie Bahou, MD
SUNY – Stony Brook University

We propose to create a multi-user facility that will support 25 funded investigators and eight investigators seeking funding, as a single-point-of-entry resource to broadly provide scientific and educational support in stem cell processing, gene transfer and analysis. Specifically, we propose to leverage pre-existing University facilities to create three distinct, but overlapping, core facilities, focusing on (1) Stem Cell Processing and Education, (2) Stem Cell Gene Transfer and (3) Stem Cell Analysis. Generation of these facilities requires one-time renovation and equipment costs to create state-of-the-art refurbished laboratories, followed by operational costs for facilities support in subsequent years. The ability to leverage pre-existing University resources will create a value-added infrastructure that will synergistically enhance the quality and breadth of stem cell research and education facilities for the local and regional Long Island biomedical research community. The creation of symposia and pilot/feasibility grants will provide fora for exchange of ideas, and will serve to attract new users into the facility.

Innovative aspects of the Stony Brook Stem Cell Center include application of unique expertise and resources in proteomics and genomics to characterize stem cells; and development of a unique educational resource for students, teachers and the local community, thereby providing hands-on instructional venues to train and support a specialized workforce pursuing commercialization of nascent technologies related to stem cell research

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Western New York Stem Cell Culture and Analysis Center

Richard Gronostajski, PhD
SUNY – University at Buffalo

We will create a Western New York Stem Cell Culture and Analysis Center at the University at Buffalo to promote and facilitate research in the use of mouse and human embryonic, adult, induced pluripotent, and cancer stem cells. These types of stem cells have tremendous potential for our understanding and treatment of human diseases, including Diabetes, Cancers, Spinal Cord injury, Parkinson's disease, Cardiomyopathies, Neurodegenerative diseases and the damage or degeneration of various organs due to aging or injury. The Center will promote stem cell research by providing highly-specialized, well-managed and easy to use resources to: 1) obtain, culture, expand and store stem cells, 2) generate new stem cells by genetic reprogramming of somatic cells, 3) tanalyze stem cells in terms of their growth, differentiation and tumorigenic characteristics, and ability to repopulate and heal organs in mice and other animals and 4) determine the genes and regulatory regions responsible for the growth and differentiated characteristics of stem cells and their progeny. Specialized facilities are needed for these functions in order to speed and maximize research efforts by scientists currently using stem cells, and to create an easy access point for new investigators to begin to use stem cells in their research. Such a Center will be used both by scientists in New York State and also by those in surrounding regions who want to begin using stem cells in their research. The Center will be composed of 4 Core Facilities:

1) Stem Cell Culture, Banking and Training Facility.
2) Induced Pluripotent Stem Cell Generation Facility.
3) Stem Cell Engraftment Facility.
4) Stem Cell Sequencing/Epigenomics Facility.

The Center will ensure that all work is performed in keeping with current federal and state scientific and ethical standards.

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Upstate Stem Cell cGMP Facility

Stephen Dewhurst, PhD
University of Rochester

Current Good Manufacturing Practices (cGMP) are the procedures that biotech companies must follow to ensure that the products they produce meet U.S. Food and Drug Administration (FDA) standards for composition, purity, potency and quality. Meeting these standards requires highly specialized, dedicated facilities that can be used to manufacture various kinds of products for human use, including stem cells.  At present, no cGMP manufacturing facilities are available for human stem cell products in upstate New York.  This creates a roadblock to the development of new stem cell medicines. The Upstate Stem Cell cGMP Facility will overcome this roadblock and accelerate the clinical application of stem cell research in Upstate N.Y.

Users of this facility will include stem cell scientists throughout upstate N.Y., and their colleagues/collaborators at other New York institutions. This proposal has three specific objectives:
1. To create and operate a cell-based GMP facility to support stem cell research in upstate New York. The facility will provide specialized laboratories for the isolation, propagation and distribution of human stem cells and their derivatives.
2. To accelerate stem cell clinical trial activity in upstate New York. The facility will promote early phase clinical trial activity by producing cGMP grade products for human use. The facility will also provide expert guidance on regulatory requirements and interactions with government regulatory bodies.
3. To facilitate collaboration between stem cell researchers in upstate New York. The facility will facilitate new scientific collaborations between stem cell researchers throughout upstate New York.

We will pro-actively reach out to upstate stem cell researchers, to understand their needs and market facility services. We will also facilitate interactions between upstate stem cell researchers, through an “annual Upstate stem cell medicine” conference that will leverage the recently created UPSTEM consortium.


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