Type III CIRM Stem Cell Research Training Program
This application is to renew our CIRM type III program to train post-doctoral scientists. Our faculty direct a large stem cell research and teaching enterprise that comprises over 100 biologists, chemists, engineers and clinicians with extensive expertise in stem cell biology and in allied disciplines dedicated to stem cell-based therapies for cardiovascular, neurodegenerative, hematopoietic and metabolic disorders. Our current CIRM program curriculum included intensive lecture courses on Stem Cell Biology, and Ethics, Intellectual Property and Regulatory Affairs and a hands-on, intensive laboratory course required of all trainees. The program also funded instructors to provide specialized workshops in hESC techniques and our trainees attended local and statewide trainee meetings to augment interchange and education. In addition, the training program provided a research stipend to defray the costs of the trainees’ research and, in some cases, the presence of CIRM trainees established hESC biology in mentors’ laboratories. The proposed program will feature the following: • Train a steady state of 6 postdoctoral fellows/year, with PhD and/or MD degrees, admitted on a competitive basis. • Mandatory lecture and laboratory courses on Stem Cell Biology as well as Ethics, Intellectual Property and Regulatory Affairs. • New elective courses in translational fields of drug discovery, animal physiology and degenerative disease models. • Student/faculty journal clubs on stem cell biology. • Institutional commitment for the training program will continue by providing support for faculty mentors, instrumentation and laboratory space dedicated to hESC and hIPSC biology, in particular in the areas of hESC/hIPSC engineering, automated small molecule, siRNA and microRNA screening, and proteomics. • Research training emphasis will be on stem cell engineering, directed differentiation and drug discovery. With this renewal, there will be an increased emphasis on providing training in translational research involving pharmacology, physiology and animal disease models used to study stem cell-based regeneration. The program is designed to offer comprehensive training in stem cell research and allied disciplines required to translate basic discoveries to clinic, biotechnology and pharmaceutical settings. Our Faculty are dedicated to excellence in research and are committed to providing outstanding postdoctoral training.
Benefits will accrue to California through: 1. California patients will benefit from improved therapies. The CIRM training program will produce highly trained stem cell scientists that will expand the number of talented researchers working towards therapies for degenerative and other disorders. 2. Technology transfer to California institutions. Our institution, as well as [REDACTED], has seen and implemented a steady increase in technology transfer in the past decade. The training provided to our best postdoctoral fellows will increase the quality and also the quantity of stem cell research at our institution. The translational potential of stem cell research and the motivation of our scientists and administrators to translate the basic discoveries to biotech and pharmaceutical settings is likely to result in licensing of further technology to the corporate sector. This will have an impact on boosting the competitiveness of our state’s technology sector with the accompanying potential for creation of new jobs. 3. Enhanced ability of California institutions to recruit stem cell scientists. Already, we have seen an increase in the number of recruits, at all levels, as a result of CIRM funding. Training grant funding is likely to contribute to overall recruitment by the prospect of placing highly trained scientists in laboratories. Moreover, because of the translational nature of the research and resulting technology transfer to industry partners, the increased number of highly trained graduates should have a similar impact on our biotechnology and/or pharmaceutical companies.
In year 3, the training grant funded the stipends of 6 postdoctoral trainees, enabling them to receive training in human stem cell biology relevant to regenerative medicine. Projects included skeletal muscle stem cell renewal, use of stem cells to understand the developmental basis of Alzheimer's Disease, development of drugs for blood vessel regeneration, and pancreatic beta cell regeneration for Diabetes. Overall, the program supports the training of a new generation of stem cell researchers, some with clinical training, and also expanded the ability of our research laboratories to engage in regenerative medicine and create the researchers of the future.
Administrative accomplishments by the Program included:
- A multi-institutional course in stem cell biology, research ethics, and legal/business issues relevant to stem cell biology and regenerative medicine that was taught in conjunction with similar CIRM programs at the Salk Institute, the Scripps Research Institute, and the University of California, San Diego.This interdisciplinary lecture/discussion course was developed specifically for this program to cover human embryonic and other stem cells and their uses in basic science, translation, and clinical research and application. The course has units on basic embryology and on specific clinical applications.
- The Training Program conducted a search for new trainees. 6 new trainees were selected following a competitive application process.
- A one-day retreat was organized at which trainees presented their research to colleagues, and discussed emerging technologies and advances in regenerative medicine.
- A stem cell seminar series and a trainee seminar series
- The program funded trainees to attend up to one nationally recognized scientific meeting annually.
Scientific accomplishments by our trainees included:
- Discovery of a gene that enhances dopaminergic neuron production by human stem cells in a Parkinson’s Disease model, Shing Fai Chan (PLoS One, 2011).
- Discovery of a method to produce skeletal muscle cells directly from human pluripotent stem cells, Sonia Albini (Cell Reports, 2012)
- Identification of drugs that activate pancreatic beta cell differentiation, Ron Piran (ACS Chemical Biology, 2013).
- Discovery of the biological mechanism that senses stretch in heart muscle and hence contributes to heart failure, Cecilia Hurtado and Ke Wei (both trainees) (Nature, 2012).
- Synthesis and characterization of a new drug-like molecule that induces cardiomyocytes from human pluripotent stem cells, Erik Willems (Cell Stem Cell, 2012)
The Director administered the program with the support of an Executive Committee consisting of Fred Levine, MD, PhD, Alessandra Sacco, PhD, Guy Salvesen, PhD, and Evan Snyder, MD, PhD. The Executive Committee advised the Director on the 1) selection of trainees for appointment, 2) select faculty for appointment and evaluate participation, 3) long-range direction of the program, 4) review the curricula and course requirements and, importantly, 5) trainee progress.
This fiscal year, the training grant funded the stipends of 6 postdoctoral trainees, enabling them to receive training in human stem cell biology relevant to regenerative medicine. Projects included skeletal muscle stem cell renewal, use of stem cells to understand the development basis of bipolar disorder and create new tools to diagnose the disease, and development of drugs for blood vessel regeneration. Overall, the program supported the training of a new generation of stem cell researchers, some with clinical training, and also expanded the ability of our research laboratories to engage in regenerative medicine and create the researchers of the future.
This annual progress report documents the activities of the CIRM-funded type 3 grant to train postdoctoral scientists at the Sanford-Burnham Medical Research Institute (SBMRI). SBMRI faculty direct a large stem cell research and teaching enterprise that comprises over 100 biologists, chemists, engineers and clinicians with extensive expertise in stem cell biology and in allied disciplines dedicated to stem cell-based therapies for cardiovascular, neurodegenerative, hematopoietic and metabolic disorders.
During the past fiscal year, the SBMRI CIRM training program trained 6 postdoctoral fellows who were selected from an applicant pool by a committee of faculty who are experts in stem cell biology and experienced mentors of young scientists. The trainees conducted research on stem cell engineering, directed differentiation and drug discovery. Most of the Trainees’ projects focused on the use of stem cells to treat degenerative diseases, although a few use patient specific stem cells to develop therapies for other diseases.
In addition, the program organized lecture, journal club and laboratory courses jointly with similar CIRM programs at the Salk Institute, Scripps Research Institute and the University of California, San Diego. Our curriculum included intensive lecture courses on Stem Cell Biology (>48 hours lectures), and Ethics, Intellectual Property and Regulatory Affairs (>20 hours lectures) and a 3-week hands-on, intensive laboratory courses. These core courses were required of all CIRM trainees at the four institutions. The program also funded instructors to provide specialized workshops in hESC techniques and we co-hosted a retreat of all CIRM program trainees in Salk Institute, Scripps Research Institute and the University of California, San Diego. Our trainees also attended local La Jolla and CIRM statewide trainee meetings to augment interchange and education. In addition, the training program provided a research stipend to defray the costs of the trainees’ research.
The program is designed to offer comprehensive training in stem cell research and allied disciplines required to translate basic discoveries to clinic, biotechnology and pharmaceutical settings. The program created an enduring benefit to stem cell research by introducing new technology into established laboratories, and training a new generation of scientists.
- RNA (2015) Genome-wide detection of high abundance N6-methyladenosine sites by microarray. (PubMed: 26092943)
- Cell Death Dis (2014) Pharmacological induction of pancreatic islet cell transdifferentiation: relevance to type I diabetes. (PubMed: 25077543)
- Nat Cell Biol (2014) N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. (PubMed: 24394384)
- Exp Mol Med (2013) Implications and limitations of cellular reprogramming for psychiatric drug development. (PubMed: 24232258)
- Biomolecules (2013) Regulation of Mammalian Gene Dosage by Long Noncoding RNAs. (PubMed: 24970160)
- EMBO J (2012) Signal-dependent incorporation of MyoD-BAF60c into Brg1-based SWI/SNF chromatin-remodelling complex. (PubMed: 22068056)
- Genes Dev (2012) Whole-genome microRNA screening identifies let-7 and mir-18 as regulators of germ layer formation during early embryogenesis. (PubMed: 23152446)
- Curr Protoc Stem Cell Biol (2012) Serum-free generation of multipotent mesoderm (kdr(+)) progenitor cells in mouse embryonic stem cells for functional genomics screening. (PubMed: 23154934)
- Cell Stem Cell (2012) Small Molecule-Mediated TGF-beta Type II Receptor Degradation Promotes Cardiomyogenesis in Embryonic Stem Cells. (PubMed: 22862949)
- Pigment Cell Melanoma Res (2012) SOX2 modulates levels of MITF in normal human melanocytes, and melanoma lines in vitro. (PubMed: 22571403)
- Cell Stem Cell (2011) Human ESC-Derived Neural Crest Model Reveals a Key Role for SOX2 in Sensory Neurogenesis. (PubMed: 21549328)
- Biol Cell (2011) Characterization of a novel angiogenic model based on stable, fluorescently labeled endothelial cell lines amenable to scale-up for high content screening. (PubMed: 21732911)
- Stem Cells Int (2011) DMSO-Free Programmed Cryopreservation of Fully Dissociated and Adherent Human Induced Pluripotent Stem Cells. (PubMed: 21716669)
- PLoS One (2010) Early acquisition of neural crest competence during hESCs neuralization. (PubMed: 21085480)
- Stem Cells (2010) Pancreatic beta-cell neogenesis by direct conversion from mature alpha-cells. (PubMed: 20653050)
- Protein Sci (2010) Homology modeling and deletion mutants of human nicotinamide mononucleotide adenylyltransferase isozyme 2: new insights on structure and function relationship. (PubMed: 20954240)
- Exp Cell Res (2010) SWI/SNF complexes, chromatin remodeling and skeletal myogenesis: it's time to exchange! (PubMed: 20553711)