Year 3
The Sanford-Burnham Medical Research Institute (SBRMI) Stem Cell Research Center (SCRC) has been able to support stem cell research in San Diego by (1) serving as an epicenter for education, training, data exchange, & collaborations; (2) providing cutting-edge stem cell technology-based services; (3) providing comprehensive systems biology tools; (4) supporting & accelerating translational research; (5) bridging basic stem cell research & drug development & screening. SCRC has been ably fulfilling its missions: (1) to study stem cell as one component in a series of intrinsic developmental programs; (2) to establish disease models using stem cells by understanding how the perturbations of the stem cell biology contribute to disease; (3) to translate potential stem cell-mediated therapies rationally to clinical practice. Under the directorship of Dr. Evan Snyder, the SCRC has obtained CIRM funding to expand to 3000 ft2 in 2 locations & engage > 60 labs across the Mesa in aspects of stem cell research, involve >150 investigators, & service many academic & private sector entities in San Diego. >60 peer-reviewed stem cell relevant papers were published in 2011 alone at SBMRI, many of which were the outcome of the collaborations between labs & appeared in the top-tier journals. Most gratifyingly, the SCRC has become a “harbor” for collaboration between labs & even institutions.
To reflect the increasingly diverse & multidisciplinary nature of the stem cell field, SCRC is organized into 4 integrated sub-cores, each with its own goals & research tasks.
Sub-Core 1: Cell generation, culture, manipulation & supply. The goal for this sub-core is to provide support for stem cell related research including facility, reagents, human embryonic stem cell (hESC) & induced pluripotent Stem Cell (hiPSC) lines, & advanced tools & services. It has become the main source for scientists to obtain high-quality & application tested stem cell culture reagents. The advanced hiPSC reprogramming service has attracted hundreds of projects from research institutes across the Mesa as well as from biotech/pharmaceutical companies. The expansion of the shared hESC, hiPSC (& their starting cells) & somatic stem cell lines housed at SCRC has provided a large pool from which researchers may choose. The Sub-Core is also developing proprietary methods for generating specific types of cells from human stem cells, e.g., neurons & pancreatic ß-cells, which will serve to facilitate disease modeling for drug screening as well as accelerating pre-clinical translational studies that might lead to the filing of INDs. A cryopreservation service also operates within this sub-core.
Sub-Core 2: Cell characterization. To affirm pluripotence, the SCRC routinely performs pluripotency marker immunodetection assays as well as in vitro differentiation capability assays & genetic profiling (the PluriTest). An in vivo teratoma formation service has also been established. Collaborating with other core in SBMRI, SCRC performs more systematic analysis on the stem cell DNA, mRNA, proteins & their modification as well as its metabolomics & pharmacogenomics. Currently, we have compiled the largest, most comprehensive comparative proteomic dataset on stem cell & its pure neurectodermal derivatives. Recently, SCRC introduced microRNA screening & analysis, a new powerful tool. Novel insights into potential drug targets have been gleaned in this manner.
Sub-Core 3: High-Throughput (HT) technologies. Interfacing with the Institute’s Prebys Chemical Genomics Center & utilizing state-of-the-art high-resolution, high-content, HT cellular imaging microscopy developed at SBMRI, the SCRC is able to (1) provide adequate numbers of human pluripotent stem cells with specific reporters as ‘biosensors’ or iPSC lines that bear disease relevant mutations; (2) differentiate hESCs/hiPSCs toward desired lineages; (3) identify tightly disease-associated assayable phenotypes; (4) develop cell activity or phenotype-based assays for large compound library screening. In this manner, users can not only discover new candidate drugs but also screen for drug toxicities.
Sub-Core 4: Training, Education & Data Sharing. Being a training facility, SCRC provides various free ad hoc short training courses including hESC/hiPSC maintenance, hiPSC generation, lineage-specific differentiation, etc. SCRC hosts the monthly Southern California Stem Cell Consortium, a monthly stem cell User’s meeting; a monthly Journal Club – all designed to engage researchers & trainees throughout the region. On the easy-to-use SCRC website, new protocols for stem cell differentiation & somatic cell reprogramming have been added to the previously posted protocols for hESC maintenance & characterization. Equally important, SCRC opens its door to the public at any time. SCRC conducts numerous tours to non-stem cell scientists, patient advocates, journalists, donors, high school students, & residents from the local communities.